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Sample records for rat fetal testis

  1. Establishing the "Biological Relevance" of Dipentyl Phthalate Reductions in Fetal Rat Testosterone Production and Plasma and Testis Testosterone Levels.

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    Gray, Leon Earl; Furr, Johnathan; Tatum-Gibbs, Katoria R; Lambright, Christy; Sampson, Hunter; Hannas, Bethany R; Wilson, Vickie S; Hotchkiss, Andrew; Foster, Paul M D

    2016-01-01

    Phthalate esters (PEs) constitute a large class of compounds that are used for many consumer product applications. Many of the C2-C7 di-ortho PEs reduce fetal testicular hormone and gene expression levels in rats resulting in adverse effects seen later in life but it appears that relatively large reductions in fetal testosterone (T) levels and testis gene expression may be required to adversely affect reproductive development (Hannas, B. R., Lambright, C. S., Furr, J., Evans, N., Foster, P. M., Gray, E. L., and Wilson, V. S. (2012). Genomic biomarkers of phthalate-induced male reproductive developmental toxicity: a targeted RT-PCR array approach for defining relative potency. Toxicol. Sci. 125, 544-557). The objectives of this study were (1) to model the relationships between changes in fetal male rat plasma testosterone (PT), T levels in the testis (TT), T production (PROD), and testis gene expression with the reproductive malformation rates, and (2) to quantify the "biologically relevant reductions" (BRRs) in fetal T necessary to induce adverse effects in the offspring. In the fetal experiment, Harlan Sprague-Dawley rats were dosed with dipentyl phthalate (DPeP) at 0, 11, 33, 100, and 300 mg/kg/day from gestational days (GD) 14-18 and fetal testicular T, PT levels, and T Prod and gene expression were assessed on GD 18. In the postnatal experiment, rats were dosed with DPeP from GD 8-18 and reproductive development was monitored through adulthood. The dose-response curves for TT levels (ED(50) = 53 mg/kg) and T PROD (ED(50) = 45 mg/kg) were similar, whereas PT was reduced at ED50 = 19 mg/kg. When the reductions in TPROD and Insl3 mRNA were compared with the postnatal effects of in utero DPeP, dose-related reproductive alterations were noted when T PROD and Insl3 mRNA were reduced by >45% and 42%, respectively. The determination of BRR levels may enable risk assessors to utilize fetal endocrine data to help establish points of departure for

  2. Mechanisms underlying the anti-androgenic effects of diethylhexyl phthalate in fetal rat testis

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    Boberg, Julie; Metzdorff, Stine Broeng; Vinggaard, Anne

    2006-01-01

    testosterone production. The present study investigated the effects of four different doses of DEHP on fetal testicular histopathology, testosterone production and expression of proteins and genes involved in steroid synthesis in fetal testes. Pregnant Wistar rats were gavaged from GD 7 to 21 with vehicle, 10...

  3. Evaluation of the effects of deltamethrin on the fetal rat testis.

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    Saillenfait, Anne-Marie; Ndiaye, Dieynaba; Sabaté, Jean-Philippe; Denis, Flavien; Antoine, Guillaume; Robert, Alain; Rouiller-Fabre, Virginie; Moison, Delphine

    2016-11-01

    Pregnant Sprague-Dawley rats were administered deltamethrin, at doses 0.1, 1, 5 or 10 mg kg(-1)  day(-1) , or di-n-hexyl phthalate (DnHP) (250 mg kg(-1)  day(-1) ), by gavage, from gestational day 13 to 19. Maternal toxicity was observed at 10 mg kg(-1)  day(-1) , as evidenced by transient clinical signs of neurotoxicity and reductions in body weight, body weight gain and corrected weight gain. Deltamethrin had no statistically significant effect on the incidence of post-implantation loss, fetal weight or anogenital distance in the male fetuses. Unlike DnHP, deltamethrin induced no changes in the expression of several genes involved in cholesterol transport or in the steroid synthesis pathway in the testes of gestational day 19.5 male fetuses (SRB1, StAR, P450scc, 3βHSD, P450 17 A1, 17βHSD). Fetal testicular levels of P450scc and P450 17 A1 protein were also unaffected by deltamethrin. No statistically significant differences were observed in the ex vivo fetal testicular production of testosterone and androstenedione after deltamethrin exposure, whereas DnHP markedly reduced these parameters. The deltamethrin metabolite, 3-phenoxybenzoic acid, was detected in amniotic fluid. In summary, our results demonstrate that in utero exposure to deltamethrin during the period of sexual differentiation had no significant effect on the testosterone synthesis pathway in the male rat fetus up to a maternal toxic dose. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  4. Diisobutyl phthalate has comparable anti-androgenic effects to di-n-butyl phthalate in fetal rat testis

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    Boberg, Julie; Petersen, Marta Axelstad; Vinggaard, Anne;

    2006-01-01

    Phthalates are widely used as plasticizers in various consumer products and building materials. Some of the phthalates are known to interfere with male reproductive development in rats, and di-n-butyl phthalate (DBP), diethylhexyl phthalate (DEHP) and butyl benzyl phthalate (BBP) were recently...... banned for use in toys in the EU mainly due to their reproductive toxicity. Diisobutyl phthalate (DiBP) has similar structural and application properties as DBP. and is being used as a substitute for DBR However, knowledge on male reproductive effects of DiBP in experimental animals is lacking, Methods...

  5. Ibuprofen results in alterations of human fetal testis development

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    Ben Maamar, Millissia; Lesné, Laurianne; Hennig, Kristin; Desdoits-Lethimonier, Christèle; Kilcoyne, Karen R.; Coiffec, Isabelle; Rolland, Antoine D.; Chevrier, Cécile; Kristensen, David M.; Lavoué, Vincent; Antignac, Jean-Philippe; Le Bizec, Bruno; Dejucq-Rainsford, Nathalie; Mitchell, Rod T.; Mazaud-Guittot, Séverine; Jégou, Bernard

    2017-01-01

    Among pregnant women ibuprofen is one of the most frequently used pharmaceutical compounds with up to 28% reporting use. Regardless of this, it remains unknown whether ibuprofen could act as an endocrine disruptor as reported for fellow analgesics paracetamol and aspirin. To investigate this, we exposed human fetal testes (7–17 gestational weeks (GW)) to ibuprofen using ex vivo culture and xenograft systems. Ibuprofen suppressed testosterone and Leydig cell hormone INSL3 during culture of 8–9 GW fetal testes with concomitant reduction in expression of the steroidogenic enzymes CYP11A1, CYP17A1 and HSD17B3, and of INSL3. Testosterone was not suppressed in testes from fetuses younger than 8 GW, older than 10–12 GW, or in second trimester xenografted testes (14–17 GW). Ex vivo, ibuprofen also affected Sertoli cell by suppressing AMH production and mRNA expression of AMH, SOX9, DHH, and COL2A1. While PGE2 production was suppressed by ibuprofen, PGD2 production was not. Germ cell transcripts POU5F1, TFAP2C, LIN28A, ALPP and KIT were also reduced by ibuprofen. We conclude that, at concentrations relevant to human exposure and within a particular narrow ‘early window’ of sensitivity within first trimester, ibuprofen causes direct endocrine disturbances in the human fetal testis and alteration of the germ cell biology. PMID:28281692

  6. Pluripotent male germline stem cells from goat fetal testis and their survival in mouse testis.

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    Hua, Jinlian; Zhu, Haijing; Pan, Shaohui; Liu, Chao; Sun, Junwei; Ma, Xiaoling; Dong, Wuzi; Liu, Weishuai; Li, Wei

    2011-04-01

    Male germline stem cells (mGSCs) are stem cells present in male testis responsible for spermatogenesis during their whole life. Studies have shown that mGSCs can be derived in vitro and resemble embryonic stem cells (ESCs) properties both in the mouse and humans. However, little is know about these cells in domestic animals. Here we report the first successful establishment of goat GSCs derived from 2-5-month fetal testis, and developmental potential assay of these cells both in vitro and in vivo. These cells express pluripotent markers such as Oct4, Sox2, C-myc, and Tert when cultured as human ESCs conditions. Embryoid bodies (EBs) formed by goat mGSCs were induced with 2 × 10(-6) M retinoic acid (RA). Immunofluorescence analysis showed that some cells inside of the EBs were positive for meiosis marker-SCP3, STRA8, and germ cell marker-VASA, and haploid marker-FE-J1, PRM1, indicating their germ cell lineage differentiation. Some cells become elongated sperm-like cells after induction. Approximately 34.88% (30/86) embryos showed cleavage and four embryos were cultured on murine fibroblast feeder and formed small embryonic stem like colonies. However, most stalled at four-cell stage after intracytoplasmic sperm injection (ICSI) of these cells. Transplantation of DAPI labeled mGSCs into the seminiferous tubules of busulfan-treated mice, and showed that mGSCs can colonize, self-renew, and differentiate into germ cells. Thus, we have established a goat GSC cell line and these cells could be differentiated into sperm-like cells in vivo and sperms in vitro, providing a promising platform for generation of transgenic goat for production of specific humanized proteins.

  7. Biology of the Sertoli Cell in the Fetal, Pubertal, and Adult Mammalian Testis.

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    Chojnacka, Katarzyna; Zarzycka, Marta; Mruk, Dolores D

    A healthy man typically produces between 50 × 10(6) and 200 × 10(6) spermatozoa per day by spermatogenesis; in the absence of Sertoli cells in the male gonad, this individual would be infertile. In the adult testis, Sertoli cells are sustentacular cells that support germ cell development by secreting proteins and other important biomolecules that are essential for germ cell survival and maturation, establishing the blood-testis barrier, and facilitating spermatozoa detachment at spermiation. In the fetal testis, on the other hand, pre-Sertoli cells form the testis cords, the future seminiferous tubules. However, the role of pre-Sertoli cells in this process is much less clear than the function of Sertoli cells in the adult testis. Within this framework, we provide an overview of the biology of the fetal, pubertal, and adult Sertoli cell, highlighting relevant cell biology studies that have expanded our understanding of mammalian spermatogenesis.

  8. Comparison of ex vivo DSP and in vitro MBP Exposures on Fetal Testis Testosterone Production

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    In utero exposure to di‐butyl phthalate (DBP) during sex differentiation reduces androgen production and produces a characteristic profile of gene expression changes in the fetal testis. The DPB metabolite mono‐butyl phthalate (MBP) is hypothesized to produce these changes by ...

  9. Comparison of ex vivo DSP and in vitro MBP Exposures on Fetal Testis Testosterone Production

    Science.gov (United States)

    In utero exposure to di‐butyl phthalate (DBP) during sex differentiation reduces androgen production and produces a characteristic profile of gene expression changes in the fetal testis. The DPB metabolite mono‐butyl phthalate (MBP) is hypothesized to produce these changes by ...

  10. Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model

    DEFF Research Database (Denmark)

    van den Driesche, Sander; Macdonald, Joni; Anderson, Richard A

    2015-01-01

    Most common male reproductive disorders are linked to lower testosterone exposure in fetal life, although the factors responsible for suppressing fetal testosterone remain largely unknown. Protracted use of acetaminophen during pregnancy is associated with increased risk of cryptorchidism in sons......, but effects on fetal testosterone production have not been demonstrated. We used a validated xenograft model to expose human fetal testes to clinically relevant doses and regimens of acetaminophen. Exposure to a therapeutic dose of acetaminophen for 7 days significantly reduced plasma testosterone (45......% reduction; P = 0.025) and seminal vesicle weight (a biomarker of androgen exposure; 18% reduction; P = 0.005) in castrate host mice bearing human fetal testis xenografts, whereas acetaminophen exposure for just 1 day did not alter either parameter. Plasma acetaminophen concentrations (at 1 hour after...

  11. Thyroid hormone function in the rat testis

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    Ying eGao

    2014-11-01

    Full Text Available Thyroid hormones are emerging regulators of testicular function since Sertoli, germ and Leydig cells are found to express thyroid hormone receptors. These testicular cells also express deiodinases which are capable of converting the pro-hormone T4 to the active thyroid hormone T3, or inactivating T3 or T4 to a non-biologically active form. Furthermore, thyroid hormone transporters are also found in the testis. Thus, the testis is equipped with the transporters and the enzymes necessary to maintain the optimal level of thyroid hormone in the seminiferous epithelium, as well as the specific thyroid hormone receptors to execute thyroid hormone action in response to different stages of the epithelial cycle of spermatogenesis. Studies using genetic models and/or goitrogens (e.g., PTU (propylthiouracil have illustrated a tight physiological relationship between thyroid hormone and testicular function, in particular Sertoli cell differentiation status, mitotic activity, gap junction function and blood-testis barrier (BTB assembly. These findings are briefly summarized and discussed herein.

  12. Human fetal testis Leydig cell disruption by exposure to the pesticide dieldrin at low concentrations.

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    Fowler, Paul A; Abramovich, David R; Haites, Neva E; Cash, Phillip; Groome, Nigel P; Al-Qahtani, Ahmed; Murray, Tessa J; Lea, Richard G

    2007-11-01

    Declining human reproductive health over the last 60 years has been proposed to be due to effects of environmental chemicals, especially endocrine disrupting compounds, on fetal development. We investigated whether a model pesticide, dieldrin, at concentrations within both maternal circulation and environmental ranges (1 pmol/l = 0.0004 p.p.b. = 380.9 pg/l), could disrupt the human fetal testis. Human fetal testes were collected during the second trimester, a critical period of male sexual differentiation (development and masculinization). Testis explants were cultured for 24 h in the presence and absence of LH (10-1000 IU LH/l) and dieldrin (1 pmol and 1 nmol/l). Endocrine, immunohistological and proteome characteristics of the tissues were investigated. Exposure to dieldrin reduced LH-induced testosterone secretion (P Dieldrin altered proteins associated with cancer, apoptosis, transcription and development. Wnt-2b was reduced 3-fold and immunolocalized to Leydig and Sertoli cells. Dieldrin also reversed some LH-induced changes in protein expression, supporting the conclusion that Leydig cell function is at risk from environmental chemicals. Our findings indicate that exposure to very low, biologically relevant, concentrations of environmental chemicals could affect the fetal human Leydig cell, reducing testosterone secretion and potentially leading to subtle dysregulation of reproductive development and adult fecundity.

  13. Menaquinone-4 enhances testosterone production in rats and testis-derived tumor cells

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    Ohsaki Yusuke

    2011-09-01

    Full Text Available Abstract Background Vitamin K is essential for the posttranslational modification of various Gla proteins. Although it is widespread in several organs, including the testis, the function of vitamin K in these organs is not well characterized. In this study, we investigated the function of vitamin K in the testis and analyzed its role in steroidogenesis. Methods Eight-week-old male Wistar rats were fed a diet supplemented with menaquinone-4 (MK-4, 75 mg/kg diet, one of the predominant K2 vitamins present in the testis, for 5 weeks. In vivo testosterone levels of the rats' plasma and testes were measured by enzyme-linked immunosorbent assay, and in vitro testosterone levels of testis-derived tumor cells (I-10 cells maintained in Ham's F-10 medium with 10% fetal bovine serum were measured following treatment with MK-4 (0 to 100 μM at several time points. Testosterone and cellular protein levels were analyzed with respect to their effects on steroidogenesis. Results Testosterone levels in the plasma and testes of MK-4-fed rats were significantly increased compared to those of control rats, with no obvious differences in plasma luteinizing hormone levels. Secreted testosterone levels from I-10 cells were elevated by MK-4, but not by vitamin K1, in a dose-dependent manner independent of cAMP treatment. Western blot analysis revealed that expression of CYP11A, the rate-limiting enzyme in steroidogenesis, and phosphorylation levels of protein kinase A (PKA and the cAMP response element-binding protein were all stimulated by the presence of MK-4. Enhancement of testosterone production was inhibited by H89, a specific inhibitor of PKA, but not by warfarin, an inhibitor of γ-glutamylcarboxylation. Conclusions MK-4 stimulates testosterone production in rats and testis-derived tumor cells via activation of PKA. MK-4 may be involved in steroidogenesis in the testis, and its supplementation could reverse the downregulation of testosterone production in

  14. Xenoestrogens diethylstilbestrol and zearalenone negatively influence pubertal rat's testis.

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    Katarzyna Marchlewska

    2010-01-01

    Full Text Available The aim of this study was to assess the impact of xenoestrogens: diethylstilbestrol (DES and zearalenone (ZEA on rat's pubertal testis and to compare it with the effect of natural estrogen - 17beta-estradiol (E. Male Wistar rats were daily, subcutaneously injected at 5th-15th postnatal days (p.d. with E (1.25 or 12.5 mug or DES (1.25 or 12.5 mug or ZEA (4 or 40 mug or vehicle. At 16th p.d. testes were dissected, weighted, and paraffin embedded. Following parameters were assessed: diameter and length of seminiferous tubule, numbers of spermatogonia A+intermediate+B (A/In/B, preleptotene spermatocytes (PL, leptotene+zygotene+pachytene spermatocytes (L/Z/PA and Sertoli cells per testis. Testes weight, seminiferous tubule diameter and length were decreased by both doses of E, DES and ZEA. DES effect was the strongest, but its influence on testis weight and seminiferous tubule length, on the contrary to E and ZEA, was not dose-dependent. Similarly, DES in both doses had the most severe negative impact on the number of germ and Sertoli cells. The negative influence of E on germ cells was less pronounced. The negative effect of ZEA was seen only after administration of the higher dose on spermatogonia number, while DES and E decreased A/In/B number more evidently. Sertoli cell number were decreased after both doses of E. ZEA40 decreased Sertoli cell number while ZEA4 had no effect. Conclusion: exposure of prepubertal male rat to DES has the strongest detrimental effect on the developing testis in comparison to E and ZEA. Both, E and DES, decreased number of germ and Sertoli cells, diminished seminiferous tubule diameter, length and testis weight. ZEA had much more weaker effect than the potent estrogens.

  15. Changes in testosterone concentration in the fetal rabbit testis after removal of the hypothalamus (encephalectomy)

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    Proshlyakova, E.V.; Rumyantseva, O.N.; Mitskevich, M.S.

    1986-10-01

    The aim of this investigation was to obtain direct data on the role of the hypothalamus in regulation of the adrogen function of the testes in rabbit fetuses. Testosterone was determined by radioimmunoassay. Changes in testostereone concentration in rabbit fetal testis after encephalectomy and after injection of luteinizing hormone releasing hormone (LHRH) into encephalectomized fetuses is shown. Results obtained are evidence that the hypothalamus, pituitary and testes in the rabbit aged 23-25 days of prenatal development constitute a single functional system. It is concluded that in both rabbit and hog fetuses, the hypothalamus begins to regulate pituitary gonadotrophic activity after LHRH can be detected in the hypothalamus itself.

  16. Genetic ablation of androgen receptor signaling in fetal Leydig cell lineage affects Leydig cell functions in adult testis.

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    Kaftanovskaya, Elena M; Lopez, Carolina; Ferguson, Lydia; Myhr, Courtney; Agoulnik, Alexander I

    2015-06-01

    It is commonly accepted that androgen-producing fetal Leydig cells (FLC) are substituted by adult Leydig cells (ALC) during perinatal testis development. The mechanisms influencing this process are unclear. We used mice with a retinoid acid receptor 2 promoter-Cre recombinase transgene (Rarb-cre) expressed in embryonic FLC precursors, but not in postnatal testis, and a dual fluorescent Cre recombinase reporter to label FLC and ALC in vivo. All FLC in newborn testis had the recombinant, whereas the majority of LC in adult testis had the nonrecombinant reporter. Primary LC cultures from adult testis had either recombinant (20%) or nonrecombinant (80%) cells, demonstrating that the FLC survive in adult testis and their ontogeny is distinct from ALC. Conditional inactivation of androgen receptor (AR) allele using the Rarb-cre transgene resulted in a 50% increase of AR-negative LC in adult testis. The mutant males became infertile with age, with all LC in older testis showing signs of incomplete differentiation, such as a large number of big lipid droplets, an increase of finger-like protrusions, and a misexpression of steroidogenic or FLC- and ALC-specific genes. We propose that the antiandrogenic exposure during early development may similarly result in an increase of FLC in adult testis, leading to abnormal LC differentiation.

  17. Identification of a dendritic cell population in normal testis and in chronically inflamed testis of rats with autoimmune orchitis.

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    Rival, Claudia; Lustig, Livia; Iosub, Radu; Guazzone, Vanesa A; Schneider, Eva; Meinhardt, Andreas; Fijak, Monika

    2006-05-01

    Experimental autoimmune orchitis (EAO) in the rat is the primary chronic animal model for the investigation of one of the main causes of male infertility, viz., testicular inflammation. Dendritic cells (DC) are potent antigen-presenting cells that play a fundamental role in autoimmune disease. We investigated the number of DC in normal testis and examined whether DC infiltrated the testis during the development of EAO. EAO was induced by active immunization with testis homogenate and adjuvants in two strains of rat (Wistar and Sprague Dawley). The presence of DC in testis was determined, 50 and 80 days after the first immunization, by immunohistochemical staining with specific antibodies (OX-62 and CD11c), and then the total number of DC was measured by stereological analysis. Labeled cells were found only in the interstitial compartment and within granulomas of EAO animals. The number of DC in EAO testes increased compared with control rats in both strains, whereas the number of OX-62+ and CD11c+ cells in adjuvant controls remained unchanged compared with untreated rats. Interspecies variations in the quantity of DC were found, with the total number of DC per testis in untreated and adjuvant control Sprague-Dawley rats being about three times higher than that seen in Wistar rats. Moreover, the increase in DC numbers at 80 days was less prominent in EAO testes of Sprague-Dawley rats than in the Wistar strain in which EAO was more severe and showed a higher number of granulomae. Thus, we have identified the DC population in normal and chronically inflamed testis. The increase in DC observed in EAO suggests that, under inflammatory conditions, the modified action(s) of these cells is a factor in the induction of the autoimmune response in testis.

  18. Evaluation of Ciprofloxacin Cytotoxic Effect in Rat Testis

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    A. Khaki

    2007-04-01

    Full Text Available Introduction & Objective: Ciprofloxacin is a synthetic antibacterial agent belonging to the family of fluoroquinolones with a very broad spectrum against microbial pathogens, especially Gram-negative infectious diseases, that has been approved in more than 100 countries world-wide. The aim of this study was to see histopathological and cytotoxic effects of ciprofloxacin after inducement in rat testis. Materials & Methods: The twenty male wistar rat were selected and randomly divided into two groups; control (n=10 and test (n=10. The test group was received 12.5mg/kg (PO ciprofloxacin daily for sixty day; however the control group just received plate. On sixtieth day the testis tissue of rat in both groups were removed and were prepared for light microscopy and cytotoxic studies. Results: Study about cytotoxic effects was indicated that absorption of radiation rate after five day in control group was increased when as compared with experimental group, (Control: 92.8±1.5 & Test: 65±6, P<0.05 and the studies of testis tissue slices of test group showed many changes such as necrosis in spermatocyt I cells plus diameter of nuclei in spermatocyt I, was increased, (P<0.01. Conclusion: Since in our study ciprofloxacin had cytotoxic side effect on spermatocyt I cells, and rate of cell death may be increased in this cells then consequently ciprofloxacin inducement is harmful for sperm health ability parameters and due decrease fertility rates in human.

  19. Expression and localization of aromatase during fetal mouse testis development.

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    Borday, Caroline; Merlet, Jorge; Racine, Chrystèle; Habert, René

    2013-01-01

    Les androgènes et les oestrogènes sont indispensables au développement et aux fonctions du testicule. Le testicule est particulièrement sensible aux perturbateurs endocriniens pendant le développement fœtal et beaucoup de perturbateurs endocriniens agissent en modifiant la balance oestrogènes/androgènes. Physiologiquement, cette balance est régulée par une cascade enzymatique qui convertit irréversiblement les androgènes en oestrogènes. Le composant principal de cette cascade est le cytochrome p450 19A1 (appelé couramment aromatase). Le but de ce travail a été d’étudier l’expression de l’aromatase testiculaire au cours du développement fœtal chez la souris.En utilisant une approche par RT-PCR et par western blot, nous avons montré que l’aromatase est exprimée dès 12,5 jours post-conception (jpc) et que l’expression est maximum à 17,5 jpc. Deux transcripts tronqués ont également été détectés par RT-PCR. La localisation cellulaire de l’aromatase a été étudiée par immunohistologie et par immunomarquage après séparation des cellules testiculaires. Cette enzyme est très fortement exprimée dans les cellules de Leydig fœtales. Elle est également exprimée dans les gonocytes mais plus faiblement et à un niveau variable selon les cellules. En revanche, elle est indétectable dans les cellules de Sertoli.En conclusion, cette étude montre pour la première fois chez la souris que 1) l’aromatase est exprimée dès le début de l’ontogenèse testiculaire, 2) elle est exprimée dans les gonocytes suggérant que ces cellules interviennent dans l’endocrinologie testiculaire et que le rapport oestrogènes/androgènes est plus important dans les gonocytes que dans le liquide interstitiel. En outre, on sait que, chez le fœtus de rat l’aromatase est essentiellement exprimée par les cellules de Sertoli. Nous proposons de prendre en compte cette différence inter-espèces comme un nouveau concept pour comprendre les diff

  20. Anatomical relationships between testis and epididymis during the fetal period in humans (10-36 weeks postconception)

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    Favorito, LA; Sampaio, FJB

    1998-01-01

    Objective: To determine the anatomy of the epididymis and its relationship with the testis during the fetal period in normal individuals. Methods: We studied bilaterally 146 testes and epididymides taken from 73 normal fresh human fetuses ranging in age from 10 to 36 weeks postconception. The epidid

  1. Heterologous expression of rat testis GABAA receptor βt variant in Chinese hamster ovary cells

    Institute of Scientific and Technical Information of China (English)

    Shi-FengLi; Yu-GuangChen; Yuan-ChangYan; Yi-PingLi

    2004-01-01

    Aim: To study the characteristics and possible retention functionof specific sequence in the 5'-end of rat testis GABAA receptor β 3t variant, Methods: Rat testis GABAA receptor β 3t variant cDNA was cloned and inserted into two eukaryotic expression vectors of pEGFP-N1 and pEGFP-C1 respectively, which have EGFP reporter gene.

  2. Prevention of H2O2 Induced Oxidative Damages of Rat Testis by Thymus algeriensis

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    Fatma Guesmi; Hamida Beghalem; Amit K Tyagi; Manel Ben Ali; Ramla Ben Mouhoub; Houda Bellamine; Ahmed Landoulsi

    2016-01-01

    ObjectiveWe evaluate the effects ofThymus algeriensis (TEO) against hydrogen peroxide (H2O2) toxicity on body and testis weight, testis sperm count, testis lipid peroxidation, and antioxidant enzyme activities in rats. MethodsRats were treated with low (LD) and high dose (HD) of H2O2 (0.1 and 1 mmol/L) in the presence or absence of TEO (150 mg/kg). ResultsThe results exhibited a significant decrease in body weight and testis weight, in total sperm number decrease (P ConclusionH2O2 has the ability to alter the sperm function, characteristics and development of testis. However, TEO is an efficient natural agent, which can prevent the testis from H2O2-induced oxidative damage in rats.

  3. In utero exposure to environmentally relevant concentrations of PCB 153 and PCB 118 disrupts fetal testis development in sheep.

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    Krogenæs, Anette K; Ropstad, Erik; Gutleb, Arno C; Hårdnes, Nina; Berg, Vidar; Dahl, Ellen; Fowler, Paul A

    2014-01-01

    Polychlorinated biphenyls (PCB) are environmental pollutants linked to adverse health effects including endocrine disruption and disturbance of reproductive development. This study aimed to determine whether exposure of pregnant sheep to three different mixtures of PCB 153 and PCB 118 affected fetal testis development. Ewes were treated by oral gavage from mating until euthanasia (d 134), producing three groups of fetuses with distinct adipose tissue PCB levels: high PCB 153/low PCB 118 (n = 13), high PCB 118/low PCB 153 (n = 14), and low PCB 153/low PCB 118 (n = 14). Fetal testes and blood samples were collected for investigation of testosterone, testis morphology, and testis proteome. The body weight of the offspring was lower in the high PCB compared to the low PCB group, but there were no significant differences in testis weight between groups when corrected for body weight. PCB exposure did not markedly affect circulating testosterone. There were no significant differences between groups in number of seminiferous tubules, Sertoli cell only tubules, and ratio between relative areas of seminiferous tubules and interstitium. Two-dimensional (2D) gel-based proteomics was used to screen for proteomic alterations in the high exposed groups relative to low PCB 153/low PCB 118 group. Twenty-six significantly altered spots were identified by liquid chromatography (LC)-mass spectroscopy (MS)/MS. Changes in protein regulation affected cellular processes as stress response, protein synthesis, and cytoskeleton regulation. The study demonstrates that in utero exposure to different environmental relevant PCB mixtures exerted subtle effects on developing fetal testis proteome but did not significantly disturb testis morphology and testosterone production.

  4. Blueberry Extracts Protect Testis from Hypobaric Hypoxia Induced Oxidative Stress in Rats

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    Andrea Zepeda

    2012-01-01

    Full Text Available Exposure to hypobaric hypoxia causes oxidative damage to male rat reproductive function. The aim of this study was to evaluate the protective effect of a blueberry extract (BB-4 in testis of rats exposed to hypobaric hypoxia. Morphometric analysis, cellular DNA fragmentation, glutathione reductase (GR, and superoxide dismutase (SOD activities were evaluated. Our results showed that supplementation of BB-4 reduced lipid peroxidation, decreased apoptosis, and increased GR and SOD activities in rat testis under hypobaric hypoxia conditions . Therefore, this study demonstrates that blueberry extract significantly reduced the harmful effects of oxidative stress caused by hypobaric hypoxia in rat testis by affecting glutathione reductase and superoxide dismutase activities.

  5. Activin A balances Sertoli and germ cell proliferation in the fetal mouse testis.

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    Mendis, Sirisha H S; Meachem, Sarah J; Sarraj, Mai A; Loveland, Kate L

    2011-02-01

    Activin affects many aspects of cellular development, including those essential for reproductive fitness. This study examined the contribution of activin A to murine fetal testicular development, revealing contrasting outcomes of activin actions on Sertoli cells and gonocytes. Shortly after sex determination, from Embryonic Day 12.5 (E12.5) through to birth (0 dpp), the activin A subunit transcript (Inhba) level rises in testis but not ovary, followed closely by the Inha transcript (encoding the inhibitory inhibin alpha subunit). Activin receptor transcript levels also change, with Acvr1 (encoding ALK2) and Acvr2b (ActRIIB) significantly higher and lower, respectively, at 0 dpp compared with E13.5 and E15.5. Transcripts encoding the signaling mediators Smad1, Smad3, and Smad4 were higher at 0 dpp compared with E13.5 and E15.5, whereas Smad2, Smad5, and Smad7 were lower. Detection of phosphorylated (P-)SMAD2/3 in nearly all testis cell nuclei indicated widespread transforming growth factor beta (TGFB) and/or activin ligand signaling activity. In contrast to wild-type littermates, activin betaA subunit knockout (Inhba(-/-)) mice have significantly smaller testes at birth, attributable to a 50% lower Sertoli cell number and decreased Sertoli cell proliferation from E13.5. Inhba(-/-) testes contained twice the normal gonocyte number at birth, with some appearing to bypass quiescence. Persistence of widespread P-SMAD2/3 in Inhba(-/-) cells indicates other TGFB superfamily ligands are active in fetal testes. Significant differences in Smad and cell cycle regulator transcript levels correlating to Inhba gene dosage correspond to differences in Sertoli and germ cell numbers. In Inhba(-/-) testes, Cdkn1a (encoding p21(cip1)), identified previously in fetal gonocytes, was lower at E13.5, whereas Cdkn1b (encoding p(27kip1) in somatic cells) was lower at birth, and cyclin D2 mRNA and protein were lower at E15.5 and 0 dpp. Thus, activin A dosage contributes to establishing the

  6. Effects of a simulated microgravity model on cell structure and function in rat testis and epididymis

    Science.gov (United States)

    Hadley, Jill A.; Hall, Joseph C.; O'Brien, Ami; Ball, Richard

    1992-01-01

    The effect of simulated microgravity on the structure and function of the testis and epididymis cells was investigated in rats subjected to 7 days of tail suspension. Results of a histological examination revealed presence of disorganized seminiferous tubules and accumulation of large multinucleated cells and spermatids in the lumen of the epididymis. In addition, decreases in the content of testis protein and in testosterone levels in the testis, the interstitial fluid, and the epididymis were observed.

  7. Effect of mono-(2-ethylhexyl) phthalate on human and mouse fetal testis: In vitro and in vivo approaches

    Energy Technology Data Exchange (ETDEWEB)

    Muczynski, V. [Univ. Paris Diderot, Sorbonne Paris Cité, Laboratory of Development of the Gonads, Unit of Stem Cells and Radiation, BP 6, 92265 Fontenay-aux-Roses (France); CEA, DSV, iRCM, SCSR, LDRG, 92265 Fontenay-aux-Roses (France); INSERM, Unité 967, F-92265, Fontenay aux Roses (France); Cravedi, J.P. [INRA, INP, Université de Toulouse, UMR1331 TOXALIM, F-31027, Toulouse (France); Lehraiki, A.; Levacher, C.; Moison, D.; Lecureuil, C.; Messiaen, S. [Univ. Paris Diderot, Sorbonne Paris Cité, Laboratory of Development of the Gonads, Unit of Stem Cells and Radiation, BP 6, 92265 Fontenay-aux-Roses (France); CEA, DSV, iRCM, SCSR, LDRG, 92265 Fontenay-aux-Roses (France); INSERM, Unité 967, F-92265, Fontenay aux Roses (France); Perdu, E. [INRA, INP, Université de Toulouse, UMR1331 TOXALIM, F-31027, Toulouse (France); Frydman, R. [Service de Gynécologie-Obstétrique, Hôpital A. Béclère, Université Paris Sud F-92141 Clamart (France); Habert, R. [Univ. Paris Diderot, Sorbonne Paris Cité, Laboratory of Development of the Gonads, Unit of Stem Cells and Radiation, BP 6, 92265 Fontenay-aux-Roses (France); CEA, DSV, iRCM, SCSR, LDRG, 92265 Fontenay-aux-Roses (France); INSERM, Unité 967, F-92265, Fontenay aux Roses (France); and others

    2012-05-15

    The present study was conducted to determine whether exposure to the mono-(2-ethylhexyl) phthalate (MEHP) represents a genuine threat to male human reproductive function. To this aim, we investigated the effects on human male fetal germ cells of a 10{sup −5} M exposure. This dose is slightly above the mean concentrations found in human fetal cord blood samples by biomonitoring studies. The in vitro experimental approach was further validated for phthalate toxicity assessment by comparing the effects of in vitro and in vivo exposure in mouse testes. Human fetal testes were recovered during the first trimester (7–12 weeks) of gestation and cultured in the presence or not of 10{sup −5} M MEHP for three days. Apoptosis was quantified by measuring the percentage of Caspase-3 positive germ cells. The concentration of phthalate reaching the fetal gonads was determined by radioactivity measurements, after incubations with {sup 14}C-MEHP. A 10{sup −5} M exposure significantly increased the rate of apoptosis in human male fetal germ cells. The intratesticular MEHP concentration measured corresponded to the concentration added in vitro to the culture medium. Furthermore, a comparable effect on germ cell apoptosis in mouse fetal testes was induced both in vitro and in vivo. This study suggests that this 10{sup −5} M exposure is sufficient to induce changes to the in vivo development of the human fetal male germ cells. -- Highlights: ► 10{sup −5} M of MEHP impairs germ cell development in the human fetal testis. ► Organotypic culture is a suitable approach to investigate phthalate effects in human. ► MEHP is not metabolized in the human fetal testis. ► In mice, MEHP triggers similar effects both in vivo and in vitro.

  8. Exposure in utero to di(n-butyl) phthalate alters the vimentin cytoskeleton of fetal rat Sertoli cells and disrupts Sertoli cell-gonocyte contact.

    Science.gov (United States)

    Kleymenova, Elena; Swanson, Cynthia; Boekelheide, Kim; Gaido, Kevin W

    2005-09-01

    Di(n-butyl) phthalate (DBP) is commonly used in personal care products and as a plasticizer to soften consumer plastic products. Male rats exposed to DBP in utero have malformations of the male reproductive tract and testicular atrophy characterized by degeneration of seminiferous epithelium and decreased sperm production. In the fetal testis, in utero exposure to DBP reportedly resulted in reduced testosterone levels, Leydig cell aggregates, and multinucleated gonocytes (MNG). We investigated whether exposure in utero to DBP affects rat fetal Sertoli cells and compromises interactions between Sertoli and germ cells in the developing testis. Histological examination showed that MNG occurred at low frequency in the normal fetal rat testis. Exposure in utero at the dose level of DBP above estimated environmental or occupational human exposure levels significantly increased the number of these abnormal germ cells. Postnatally, MNG exhibited aberrant mitoses and were detected at the basal lamina. MNG were not apoptotic in the fetal and postnatal rat testes, as indicated by TUNEL. Sertoli cells in DBP-exposed fetal testis had retracted apical processes, altered organization of the vimentin cytoskeleton, and abnormal cell-cell contacts with gonocytes. The effect of DBP on Sertoli cell morphology at the level of light microscopy was reversed after birth and cessation of exposure. Our data indicate that fetal Sertoli cells are targeted by exposure in utero to DBP and suggest that abnormal interactions between Sertoli and germ cells during fetal life play a role in the development of MNG.

  9. Chronic Intake of Green Propolis Negatively Affecting the Rat Testis

    Science.gov (United States)

    Severi-Aguiar, Grasiela Dias de Campos; Pinto, Suellen Josine; Capucho, Cristina; Oliveira, Camila Andrea; Diamante, Maria Aparecida; Barbieri, Renata; Predes, Fabrícia Souza; Dolder, Heidi

    2017-01-01

    Background: Human and animal evidence suggests that environmental toxicants may have an adverse impact on male reproductive health, reducing the population's reproductive output. Owing to the renewed attraction for natural products, some of them constitute effective alternatives to mitigate these effects. Propolis is a candidate for this use because of its intrinsic properties. In many situations, it improved the testicular damage and alleviated the toxic effects induced by environmental contaminant exposure. Objective: The aim of this study was to investigate possible alterations of testicular parameters and certify if its use is really advantageous to the testis, since this could affect rat reproductive function. Materials and Methods: Forty-eight adult male Wistar rats were divided into four groups (Co = control, T1 = 3 mg propolis/kg/day, T2 = 6 mg/kg/day, T3 = 10 mg/kg/day) and were exposed during 56 days. The testes were assessed with morphometrical, stereological, and ultrastructural analyses. Cell proliferation and death were diagnosed, respectively, by immunocytochemistry. Connexin 43 (Cx43) and N-cadherin transcript levels were determined by reverse transcription-polymerase chain reaction. Results: Increased cell proliferation and Leydig cell volume were observed in T2, and in contrast, Cx43 upregulation and cell death were observed in T3. Both T2 and T3 showed ultrastructural abnormalities in testicular parenchyma. Conclusion: We recommend a cautious intake of propolis to avoid deleterious effects. SUMMARY Chronic intake of Brazilian green propolis induced N.-cadherin downregulation and decreased on seminiferous tubule volumeIncrease on connexin 43 expression and cell death and decrease in Leydig cell.(LC) number/testis with the concentration of 10 mg/kg/day were observedIncrease on cell proliferation, cytoplasmic proportion, and volume of LC with the concentration of 6 mg/kg/day was detectedThe presence of empty spaces between spermatids and malformed

  10. Correlation of expression of preprothyrotropin-releasing hormone and receptor with rat testis development

    Institute of Scientific and Technical Information of China (English)

    李臻; 张远强; 刘新平; 许若军

    2002-01-01

    Objective To investigate the expression regulation of thyrotrophin-releasing hormone (TRH) and TRH receptor (TRH-R), and their role in the development of rat testis.Methods Oligonucleotide primers were designed from the sequences of rat hypothalamus prepro TRH (ppTRH) and pituitary TRH-R cDNA for reverse transcription polymerase chain reaction (RT-PCR). Specific fragments of ppTRH and TRH-R cDNA were cloned and sequenced. Expression plasmids containing ppTRH and TRH-R genes were then constructed, and expression was found in E.coli DH5-α. ppTRH and TRH-R mRNA in the testis was quantitated in RNA samples prepared from rats at different developmental stages by real time quantitative RT-PCR.Results The quantitative analyses demonstrated that no ppTRH and TRH mRNA could be detected at the earliest stage (day 8). ppTRH and TRH mRNA signals were detected on day 15 and increased progressively on days 20, 35, 60 and 90. Conclusion Our results suggest that rat testis could specifically express TRH and TRH-R, and the transcriptions of ppTRH and TRH-R genes in the rat testis were development-dependent. The acquirement of expressed products for ppTRH and TRH-R can be used for further research on the physiological significance of TRH and TRH-R expression in rat testis.

  11. Maternal undernutrition does not alter Sertoli cell numbers or the expression of key developmental markers in the mid-gestation ovine fetal testis

    Directory of Open Access Journals (Sweden)

    Andrade Luis P

    2013-01-01

    Full Text Available Abstract Background The aim of this study was to determine the effects of maternal undernutrition on ovine fetal testis morphology and expression of relevant histological indicators. Maternal undernutrition, in sheep, has been reported, previously, to alter fetal ovary development, as indicated by delayed folliculogenesis and the altered expression of ovarian apoptosis-regulating gene products, at day 110 of gestation. It is not known whether or not maternal undernutrition alters the same gene products in the day 110 fetal testis. Design and methods Mature Scottish Blackface ewes were fed either 100% (Control; C or 50% (low; L of estimated metabolisable energy requirements of a pregnant ewe, from mating to day 110 of gestation. All pregnant ewes were euthanized at day 110 and a sub-set of male fetuses was randomly selected (6 C and 9 L for histology studies designed to address the effect of nutritional state on several indices of testis development. Sertoli cell numbers were measured using a stereological method and Ki67 (cell proliferation index, Bax (pro-apoptosis, Mcl-1 (anti-apoptosis, SCF and c-kit ligand (development and apoptosis gene expression was measured in Bouins-fixed fetal testis using immunohistochemistry. Results No significant differences were observed in numbers of Sertoli cells or testicular Ki67 positive cells. The latter were localised to the testicular cords and interstitium. Bax and Mcl-1 were localised specifically to the germ cells whereas c-kit was localised to both the cords and interstitium. SCF staining was very sparse. No treatment effects were observed for any of the markers examined. Conclusions These data suggest that, unlike in the fetal ovary, maternal undernutrition for the first 110 days of gestation affects neither the morphology of the fetal testis nor the expression of gene products which regulate apoptosis. It is postulated that the effects of fetal undernutrition on testis function may be expressed

  12. Blueberry Extracts Protect Testis from Hypobaric Hypoxia Induced Oxidative Stress in Rats

    Science.gov (United States)

    Zepeda, Andrea; Aguayo, Luis G.; Fuentealba, Jorge; Figueroa, Carolina; Acevedo, Alejandro; Salgado, Perla; Calaf, Gloria M.; Farías, Jorge

    2012-01-01

    Exposure to hypobaric hypoxia causes oxidative damage to male rat reproductive function. The aim of this study was to evaluate the protective effect of a blueberry extract (BB-4) in testis of rats exposed to hypobaric hypoxia. Morphometric analysis, cellular DNA fragmentation, glutathione reductase (GR), and superoxide dismutase (SOD) activities were evaluated. Our results showed that supplementation of BB-4 reduced lipid peroxidation, decreased apoptosis, and increased GR and SOD activities in rat testis under hypobaric hypoxia conditions (P < 0.05). Therefore, this study demonstrates that blueberry extract significantly reduced the harmful effects of oxidative stress caused by hypobaric hypoxia in rat testis by affecting glutathione reductase and superoxide dismutase activities. PMID:23213351

  13. METABOLOMIC EVALUATION OF RAT LIVER AND TESTIS TO CHARACTERIZE THE TOXICITY OF TRIAZOLE FUNGICIDES

    Science.gov (United States)

    The effects of two triazole fungicides, myclobutanil and triadimefon, on endogenous rat metabolite profiles in blood serum, liver, and testis was assessed using proton nuclear magnetic resonance (1H-NMR) spectroscopy. Adult male Sprague-Dawley rats were dosed daily by gavage for...

  14. Dynamic regulation of glutamic acid decarboxylase 65 gene expression in rat testis

    Institute of Scientific and Technical Information of China (English)

    Haixiong Liu; Shifeng Li; Yunbin Zhang; Yuanchang Yan; Yiping Li

    2009-01-01

    Glutamate decarboxylase 65 (GAD65) produces γ-amino-butyric acid,the main inhibitory neurotransmitter in adult mammalian brain.Previous experiments,per-formed in brain,showed that GAD65 gene possesses two TATA-less promoters,although the significance is unknown.Here,by rapid amplification of cDNA ends method,two distinct GAD65 mRNA isoforms transcribed from two independent clusters of transcription start sites were identified in post-natal rat testis.RT-PCR results revealed that the two mRNA isoforms had distinct expression patterns during post-natal testis maturation,suggesting that GAD65 gene expression was regulated by alternative promoters at the transcription level.By using GAD65-speciflc antibodies,western blotting analysis showed that the 58-kDa GAD65,N-terminal 69 amino acids truncated form of full-length GAD65 protein,was developmentally expressed during post-natal testis matu-ration,suggesting that GAD65 gene expression in testis may also be regulated by post-translational processing.Confocal immunofluorescence microscopy revealed that GAD65 protein was presented in Leydig cells of Day 1 testis,primary spermatocytes and spermatids of post-natal of Day 90 testis.The above results suggested that GAD65 gene expression is dynamically regulated at mul-tiple levels during post-natal testis maturation.

  15. Heterologous Expression of Rat Testis GABAA Receptor β3t Splicing Variant in CHO Cells

    Institute of Scientific and Technical Information of China (English)

    Shi-feng LI; Yu-guang CHEN; Yuan-chang YAN; Yi-ping LI

    2004-01-01

    Objective To characterize a possible retention function of unique sequence in the 5'end of rat testis GABAA receptor β3t splicing variantMethods Rat testis GABAA receptor β3t splicing variant cDNA was cloned and two eukaryotic expression recombinant plasmids of pEGFP-N1 and pEGFP-C1 were constructed respectively by fusing green fluorescent protein to the N or C-terminus of β3t isoform. The recombinant plasmids were transfected into CHO cells by calcium phosphate co-precipitation method. Fluorescence microscope and laser confocal microscope were used to analyze localization of β3t in the transfected cells. ConA-Texas-Red was used to label cell ER and the localization of rat testis β3t splicing variant in CHO cells was determined.Results When rat testis β3t splicing variant was expressed in CHO cells, two expression patterns were delineated, the distributions of uniform and mainly discrete intracellular compartments respectively. The chimera product failed to be translocated into the cell surface when expressed in CHO cells; whereas the β3 subunit of rat brain was incorporated into the plasma membrane.Conclusion The inability of β3t to target into the ER may be a consequence of the unique 25 specific amino acid segments in the N terminus.

  16. Effects of catuaba cristal® on the testis of wistar rats

    Directory of Open Access Journals (Sweden)

    Karine Moura de Freitas

    2011-10-01

    Full Text Available The aim of this study was to evaluate the possible beneficial effects of Catuaba Cristal® (CC, an alcoholic drink made from wine and Erythroxylum catuaba Ar. Cam on testis. Wistar rats either received CC solution (n=8 or water (n=9. Results showed significant body weight reduction within the CC group, although, no weight changes were observed for liver, kidney, testis, epididymis, seminal vesicle and prostate. The volumetric proportion and volume of interstitial tissue and lymphatic space were reduced in the treated group. In the CC group, although the nuclear volume of Leydig cells (LC decreased, the number of LC per testis increased. These results suggested that CC had no beneficial effect on spermatogenesis of Wistar rats.

  17. Ex vivo culture of human fetal gonads: manipulation of meiosis signalling by retinoic acid treatment disrupts testis development.

    Science.gov (United States)

    Jørgensen, A; Nielsen, J E; Perlman, S; Lundvall, L; Mitchell, R T; Juul, A; Rajpert-De Meyts, E

    2015-10-01

    What are the effects of experimentally manipulating meiosis signalling by addition of retinoic acid (RA) in cultured human fetal gonads? RA-treatment accelerated meiotic entry in cultured fetal ovary samples, while addition of RA resulted in a dysgenetic gonadal phenotype in fetal testis cultures. One of the first manifestations of sex differentiation is the initiation of meiosis in fetal ovaries. In contrast, meiotic entry is actively prevented in the fetal testis at this developmental time-point. It has previously been shown that RA-treatment mediates initiation of meiosis in human fetal ovary ex vivo. This was a controlled ex vivo study of human fetal gonads treated with RA in 'hanging-drop' tissue cultures. The applied experimental set-up preserves germ cell-somatic niche interactions and the investigated outcomes included tissue integrity and morphology, cell proliferation and survival and the expression of markers of meiosis and sex differentiation. Tissue from 24 first trimester human fetuses was included in this study, all from elective terminations at gestational week (GW) 7-12. Gonads were cultured for 2 weeks with and without addition of 1 µM RA. Samples were subsequently formalin-fixed and investigated by immunohistochemistry and cell counting. Proteins investigated and quantified included; octamer-binding transcription factor 4 (OCT4), transcription factor AP-2 gamma (AP2γ) (embryonic germ cell markers), SRY (sex determining region Y)-box 9 (SOX9), anti-Müllerian hormone (AMH) (immature Sertoli cell markers), COUP transcription factor 2 (COUP-TFII) (marker of interstitial cells), forkhead box L2 (FOXL2) (granulosa cell marker), H2A histone family, member X (γH2AX) (meiosis marker), doublesex and mab-3 related transcription factor 1 (DMRT1) (meiosis regulator), cleaved poly ADP ribose polymerase (PARP), cleaved Caspase 3 (apoptosis markers) and Ki-67 antigen (Ki-67) (proliferation marker). Also, proliferation was determined using a 5'-bromo-2

  18. EFFECT OF MULTIGLYCOSIDES OF TRIPTERYGIUM WILFORDH (GTW) ON RAT TESTIS, HEART, LIVER AND KIDNEY

    Institute of Scientific and Technical Information of China (English)

    ZHOULan-Fang; LEIHai-Peng

    1989-01-01

    Adult male Wistar rats were given GTW orally at 50 rag/kg or 20 mg / kg for 4 or 5 weeks. Control animals were given the vehicle only. ARer treatment, testis, heart, liver and kidney were removed and examined. The scminiferous tubules of the treated

  19. The effect of alpha-tocopherol on lipid peroxidation of microsomes and mitochondria from rat testis.

    Science.gov (United States)

    Gavazza, M B; Catalá, A

    2006-04-01

    The testis is a remarkably active metabolic organ; hence it is suitable not only for studies of lipid metabolism in the organ itself but also for the study of lipid peroxidation processes in general. The content of fatty acids in testis is high with a prevalence of polyunsaturated fatty acids (PUFA) which renders this tissue very susceptible to lipid peroxidation. Studies were carried out to evaluate the effect of alpha-tocopherol in vitro on ascorbate-Fe(++) lipid peroxidation of rat testis microsomes and mitochondria. Chemiluminescence and fatty acid composition were used as an index of the oxidative destruction of lipids. Special attention was paid to the changes produced on the highly PUFA [C20:4 n6] and [C22:5 n6]. Lipid peroxidation of testis microsomes or mitochondria induced a significant decrease of both fatty acids. Total chemiluminescence was similar in both kinds of organelles when the peroxidized without (control) and with ascorbate-Fe(++) (peroxidized) groups were compared. Arachidonic acid was protected more efficiently than docosapentaenoic acid at all alpha-tocopherol concentrations tested when rat testis microsomes or mitochondria were incubated with ascorbate-Fe(++). The maximal percentage of inhibition in both organelles was approximately 70%; corresponding to an alpha-tocopherol concentration between 1 and 0.25 mM. IC50 values from the inhibition of alpha-tocopherol on the chemiluminescence were higher in microsomes (0.144 mM) than mitochondria (0.078 mM). The protective effect observed by alpha-tocopherol in rat testis mitochondria was higher compared with microsomes, associated with the higher amount of [C20:4 n6]+[C22:5 n6] in microsomes that in mitochondria. It is proposed that the vulnerability to lipid peroxidation of rat testis microsomes and mitochondria is different because of the different proportion of PUFA in these organelles The peroxidizability index (PI) was positively correlated with the level of long chain fatty acids. The

  20. Identification and expression of GABAc receptor in rat testis and spermatozoa

    Institute of Scientific and Technical Information of China (English)

    Shifeng Li; Yunbin Zhang; Haixiong Liu; Yuanchang Yan; Yiping Li

    2008-01-01

    Our previous studies showed that γ-aminobutyric acid (GABA)A and GABAB receptors are involved in rat sperm acrosome reaction induced by progesterone or GABA. Here,we report the presence of GABAc receptor in rat testis and spermatozoa.Full-length complementary DNA encoding the ρ1,ρ2 and ρ3 subunits of GABAc receptor were cloned from rat testis;their sequences are identical to those of rat GABAc receptor in retina.Reverse transcription-polymerase chain reaction analysis showed that during the development of rat testis,the transcript levels of the ρ1 and ρ2 subunits showed little change,while the expression of ρ3 was gradually up-regulated.Immunofluorescence analysis using an anti-ρ1 antibody revealed that GABAc receptor exists on the elongated spermatid and sperm.Using a chlortetracycline assay,we found that N(4)-chloroacetylcytosine arabinoside, a GABAc receptor agonist,triggered rat sperm acrosome reaction;whereas(1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid,a GABAc receptor antagonist, inhibited the ability of N(4)-chloroacetylcytosine arabinoside to induce acrosome reaction.These results suggested that GABAc receptors are also involved in rat sperm acrosome reaction.

  1. Serum Hormone and Cellular Proliferation Changes of Testis in Rats with Experimental Orchitis Induced by Lipopolysaccharide

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To explore the changes of serum male hormone,androgen binding protein (ABP) expression as well as the proliferation of testicular cells in rats with experimental orchitis induced by bacterial lipoplysaccharide (LPS) in vivo and to elucidate the putative mechanism of LPS on Spermatogenesis of testis.Methods The serum testosterone(T),luteinizing hormone(LH) levels were detected with magnetic enzyme immunoassay.The expression of proliferating cell nuclear antigen (PCNA) and ABP expression at mRNA level of testis were studied with immunohistochemical staining and in situ hybrydization respectively.Results The serum T level in rats with experimental orchitis was significantly higher than that in the rats of control(P<0.05)and ABP mRNA expression in Sertoli cells of testis was significantly increased (P<0.05) while PCNA expression in seminiferous epithelium in experimental rats significantly was decreased as compared with that of the control(P<0.05).No significant change in serum LH level was seen between experimental orchitis and control groups (P>0.05).Conclusion The serum level of T and ABP expression significantly increased in rats with experimental aspecific orchitis induced by LPS,and at the same time inhibition of cellular proliferation of seminiferous epithelium can be detected,which may be the possible mechanism of male infertility in inflammatory process.

  2. Immunohistopathology of the contralateral testis of rats undergoing experimental torsion of the spermatic cord

    Institute of Scientific and Technical Information of China (English)

    Marcelo G. Rodriguez; Claudia Rival; María S. Theas; Livia Lustig

    2006-01-01

    Aim: To evaluate the immunohistopathological changes in the contralateral testis of rats after an experimental spermatic cord torsion. Methods: Male Sprague-Dawley rats of 45-50 days old were subjected to a 720° unilateral spermatic cord torsion for 10, 30 and 80 days (experimental group, E), respectively or sham operation (control group, C). Histopathology of the contralateral testis as well as germ cell apoptosis were studied using the Terminal Deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) technique. The number of testicular lymphocytes, mast cells and macrophages, and the expression of tumor necrosis factor-α (TNF-α) and its receptor (TNFR 1) in testicular cells of the contralateral testis were quantified by histochemistry and immunohistochemistry.TNF-o concentration in testicular fluid was determined by ELISA. Results: In the contralateral testis of rats from the E group, the maximal degree of damage of the germinal epithelium was seen 30 days after torsion. At this time we observed in the E group vs. The C group increases: (I) the number of testicular T-lymphocytes; (ii) the number of testicular mast cells and macrophages; (iii) the percentage of macrophages expressing TNF-α; (iv) TNF-α concentration in testicular fluid; (v) the number of apoptotic germ cells; and (vi) the number of TNFR1 + germ cells. Conclusion:Experimental spermatic cord torsion induces, in the contralateral testis, a focal damage of seminiferous tubules characterized by apoptosis and sloughing of germ cells. Results suggest humoral and cellular immune mediated testicular cell damage in which macrophages and mast cells seem to be involved in the induction of germ cell apoptosis through the TNF-α/TNFR1 system and in the modulation of the inflammatory process.

  3. Dose- and time-related effects of caffeine on the testis in immature male rats.

    Science.gov (United States)

    Bae, Jaeman; Choi, Hyeonhae; Choi, Yuri; Roh, Jaesook

    2017-01-27

    We previously showed that prepubertal chronic caffeine exposure adversely affected the development of the testes in male rats. Here we investigated dose- and time-related effects of caffeine consumption on the testis throughout sexual maturation in prepubertal rats. A total of 80 male SD rats were randomly divided into four groups: controls and rats fed 20, 60, or 120 mg caffeine/kg/day, respectively, via gavage for 10, 20, 30, or 40 days. Preputial separation was monitored daily before the rats were sacrificed. Terminal blood samples were collected for hormone assay, and testes were grossly evaluated and weighed. One testis was processed for histological analysis, and the other was collected to isolate Leydig cells. Caffeine exposure significantly increased the relative weight of the testis in a dose-related manner after 30 days of exposure, whereas the absolute testis weight tended to decrease at the 120 mg dose of caffeine. The mean diameter of the seminiferous tubules and height of the germinal epithelium significantly decreased in the caffeine-fed groups after 40 days of caffeine exposure, which was accompanied by a reduced BrdU incorporation rate in germ cells. In addition, caffeine intake significantly reduced in vivo and ex vivo testosterone production in a dose-related manner. Our results demonstrate that caffeine exposure during sexual maturation alter the testicular microarchitecture and also slow germ cell proliferation even at the 20 mg dose level. Furthermore, caffeine may act directly on Leydig cells and interfere with testosterone production in a dose-related manner, consequently delaying onset of sexual maturation.

  4. Studies on Expression of P1 Protamine Gene in Rat and Mouse Testis

    Institute of Scientific and Technical Information of China (English)

    费仁仁; 纪林; 吴小芳; 陈晖; 陈惠琼; 李建国; 王一飞; 闫月敏; 王莎丽; 陈啸梅; 薛社普

    1999-01-01

    Protamine is a kind small,basic protein rich in arginine residues and found to be complexed with DNA in spermatozoa. We have cloned a 150 bp cDNA encoding the rat protamine (rP) by RT-PCR technique.Dig-labelled cDNA for rP was used for Northern blot analysis to study the expression of P1 protamine gene in rat and mouse.P1 protamine mRNA was detected only in rat testis,no hybridization signals were de-tected in rat brain and lever.In addition,the presence of P1 protamine mRNA was detected not only in rat testis,but also in mouse testis.Dig-labelled cDNA for mouse protamine 1 (mP1) was used to study the expression of mP1 gene during the process of sexual maturation of mouse.7-8 d after birth,no mP1 mRNA could be detected.At d 24-26,mP1 mRNA was detectable migrating as a homogeneous band at 580 nu-cleotides,whereas in sexually mature animals,a heterogeneous mixture of RNAs ranging from 450-580 bases in length was observed.Histological studies revealed that in the testis of 7-8-day-old mouse, spermatogenesis has developed to the sperma-tocyte stage, whereas round spermatids (Rs) were present in the testis of the mice with 24-26 d age and elongating spermatids(Es)were present in the testis of sexually mature animals. Electrophoresis of total nuclear basic proteins(TNBP)revealed that the Rs could possess the somatic histones,while Es was found to have protamine and less histone.These results indicate that the P1 protamine gene is tissues-specifically ex-pressed and the P1 protamine is showing to be conservative in evolution.During the process of sexual maturation,along with morphological changes,mP1 gene was tran-scribed in Rs and translated in Es.The mechanism of protamine gene expression was discussed.

  5. Rat Testis Damage Caused by Lead Sulfide Nanoparticles After Oral Exposure.

    Science.gov (United States)

    Cao, Yanhua; Wang, Dong; Li, Qingzhao; Deng, Hongliang; Shen, Jian; Zheng, Guoying; Sun, Miao

    2016-03-01

    Lead sulfide nanoparticals (PbS NPs) is an important semiconductor material due to its unique physical and chemical properties, but its potential health hazard to reproductive system is not clear. In the current study, we systematically explored the reproductive toxicity of PbS NPs in rats by measuring the body weight and testicular coefficient, testing serum testosterone levels, and studying the sperm survival rate and sperm abnormality rate. Furthermore, in order to study the toxic mechanism we performed lead contents measurements in testis, and investigated the pathology in testis. Our results confirmed that PbS NPs showed high reproductive toxicity due to PbS NPs in rats' testicular tissue by the establishment of PbS NPs chronic exposure model.

  6. Ultrastructural interrelationship between the pineal gland and the testis in the male rat.

    Science.gov (United States)

    Kuş, I; Sarsilmaz, M; Ogetürk, M; Yilmaz, B; Keleştimur, H; Oner, H

    2000-01-01

    The ultrastructural interrelationship between the pineal gland and testis was evaluated in the rat. Wistar rats were divided into 6 groups. Groups I and II were sham-orchidectomized and orchidectomized rats, respectively. Rats in group III were orchidectomized and daily injected with testosterone propionate (TP) for 1 month. Groups IV and V were sham-pinealectomized and pinealectomized, respectively. Group VI was pinealectomized and daily injected with melatonin for 2 months. All animals were anesthetized with ketamine for fixation by vascular perfusion. Pineal glands of groups I, II, and III and the testes of groups IV, V, and VI were removed and weighed. All specimens were examined by electron microscopy. Orchidectomy caused an increase of lipid droplets, cytoplasmic dense bodies, and lysosomes. Rough endoplasmic reticulum, Golgi apparatus, and mitochondria were extensive in the cytoplasm. TP administration to orchidectomized rats resulted in formation of less extensive lipid droplets and mitochondria. In pinealectomized rats, golgi complex, mitochondria, and enlarged smooth endoplasmic reticulum were extensive in the cytoplasm of Leydig cells. Formation of cytoplasmic secretory granules and osmiophilic bodies was observed. Testicular weight increased compared to group IV. Melatonin decreased testicular weight in comparison to group V and prevented ultrastructural changes. Pinealectomy and orchidectomy caused hyperactivity in Leydig cells and pinealocytes, respectively, which suggests a mutual relationship between the pineal gland and testis in the rat.

  7. Involvement of soluble Fas Ligand in germ cell apoptosis in testis of rats undergoing autoimmune orchitis.

    Science.gov (United States)

    Jacobo, Patricia Verónica; Fass, Mónica; Pérez, Cecilia Valeria; Jarazo-Dietrich, Sabrina; Lustig, Livia; Theas, María Susana

    2012-11-01

    Experimental autoimmune orchitis (EAO) is a model of chronic inflammation and infertility useful for studying immune and germ cell (GC) interactions. EAO is characterized by severe damage of seminiferous tubules (STs) with GCs that undergo apoptosis and sloughing. Based on previous results showing that Fas-Fas Ligand (L) system is one of the main mediators of apoptosis in EAO, in the present work we studied the involvement of Fas and the soluble form of FasL (sFasL) in GC death induction. EAO was induced in rats by immunization with testis homogenate and adjuvants; control (C) rats were injected with adjuvants; a group of non-immunized normal (N) rats was also studied. Activation of Fas employing an anti-Fas antibody decreased viability (trypan blue exclusion test) and induced apoptosis (TUNEL) of GCs from STs of N and EAO rats, an effect more pronounced on GCs from EAO STs. By Western blot we detected an increase in sFasL content in the testicular fluid of rats with severe EAO compared to N and C rats. By intratesticular injection of FasL conjugated to Strep-Tag molecule (FasL-Strep, BioTAGnology) and its immunofluorescent localization, we demonstrated that sFasL is able to enter the adluminal compartment of the STs. Moreover, FasL-Strep induced GC apoptosis in testicular fragments of N rats. By flow cytometry, we detected an increase in the number of membrane FasL-expressing CD4+ and CD8+ T cells in testis during EAO development but no expression of FasL by macrophages. Our results demonstrate that sFasL is locally produced in the chronically inflamed testis and that this molecule is able to enter the adluminal compartment of STs and induce apoptosis of Fas-bearing GCs.

  8. Acute cadmium intoxication: influence of cyproterone acetate on the testis and epididymis of the rat.

    Science.gov (United States)

    Francavilla, S; Moscardelli, S; Francavilla, F; Casasanta, N; Properzi, G; Martini, M; Santiemma, V

    1981-02-01

    The changes resulting from treatment with cadmium were studied following the histological changes, the modification of both vascular permeability to vital dyes and of alkaline phosphatase activity in rat testis and epididymis. The testicular extravasation of acriflavine started 90 min following parenteral injection of cadmium and increased thereafter synchronous with an increase in testicular and epididymal weights due to edema. At 14 and 24 hr a striking decrease of interstitial fluorescence and tubular degeneration were noted in testis and caput epididymis due to thrombosis of the microvascular circulation. The barrier noted at 8 hr following cadmium injection. No changes of alkaline phosphatase activity was detected in testicular and epididymal blood vessels after cadmium injection. Previous treatment with cyproterone acetate accelerated the appearance of such alterations. The interstitial nuclear staining with acriflavine appeared in the testis at 1 hr and was diffuse at 90 and 120 min. cyproterone acetate seemed to accelerate the appearance of tubular degeneration at 8 hr after cadmium injection. The changes of the male rat gonad following cadmium treatment were characterized by an increased vascular permeability and generalized thrombosis. An inbalance of androgen stimulation seems to increase the blood vessels susceptibility to cadmium.

  9. Erdosteine protects rat testis tissue from hypoxic injury by reducing apoptotic cell death.

    Science.gov (United States)

    Guven, A; Ickin, M; Uzun, O; Bakar, C; Balbay, E Gulec; Balbay, O

    2014-02-01

    The purpose of this study was to examine the effects of hypobaric hypoxia on testis morphology and the effects of erdosteine on testis tissue. Caspase-3 and hypoxia-inducible factor 1α expressions were detected by immunohistochemistry. Adult male Wistar rats were placed in a hypobaric hypoxic chamber. Rats in the erdosteine group were exposed to the same conditions and treated orally with erdosteine (20 mg kg(-1) daily) at the same time from the first day of hypoxic exposure for 2 weeks. The normoxia group was evaluated as the control. The hypoxia group showed decreased height of spermatogenic epithelium in some seminiferous tubules, vacuolisation in spermatogenic epithelial cells, deterioration and gaps in the basal membrane and an increase in blood vessels in the interstitial area. The erdosteine group showed amelioration of both epithelial cell vacuolisation and basal membrane deterioration. Numbers of hypoxia-inducible factor 1α-immunostained Sertoli and Leydig cells were significantly higher in the hypoxia group than in the erdosteine group. The number of seminiferous tubules with caspase-3-immunostained germ cells was highest in the hypoxia group and decreased in the erdosteine and normoxia groups respectively. Based on these observations, erdosteine protects testis tissue from hypoxic injury by reducing apoptotic cell death.

  10. Desenvolvimento do testículo de camundongo da fase fetal até a idade adulta Development of the mouse testis from fetal period to adulthood

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    Rozangela de Lucca Martins Sachetim

    1999-07-01

    Full Text Available O desenvolvimento do testículo de camundongo foi estudado desde o 15º dia de gestação até a idade adulta. As lâminas preparadas para estudo histológico em microscópio óptico foram tratadas pela técnica do ácido periódico - Schiff e pela hematoxilina de Harris (PAS + H. Na fase fetal, os túbulos seminíferos estão constituídos por gonócitos e células de sustentação imaturas. No tecido intersticial, observam-se as células de Leydig. A espermatogênese inicia-se logo após o nascimento. O epitélio seminífero torna-se mais espesso aos 14 dias pós-natal, onde se observam espermatócitos em prófase meiótica. Aos 21 dias pós-natal, o epitélio seminífero contém espermatogônias, espermatócitos e células de Sertoli. As primeiras espermátides são observadas aos 28 dias pós-natal e, aos 42 dias, já ocorrem espermátides maduras. Desde os 49 dias pós-natal, são observados espermatozóides na luz dos túbulos seminíferos. A partir dos 56 dias pós-natal, o epitélio seminífero, bem como o tecido intersticial, apresentam aspecto e características típicos do testículo do camundongo adulto.The development of mouse testis was studied from 15th day of fetal life up to adult age. The prepared slides for histological study in light microscopy were stained by periodic acid - Schiff and Haematoxylin of Harris (PAS + H. The results show that in fetal life the seminiferous tubules are constituted by gonocytes and immature sustentation cells. In the interstitial tissue, Leydig cells are found. Spermatogenesis begins soon after birth. The seminiferous epithelium becomes thicker at day 14 postnatal when spermatocytes in meiotic prophase are observed. At day 21 postnatal the seminiferous epithelium contains spermatogonia, spermatocytes and Sertoli cells. The first spermatids are observed at day 28 postnatal and at day 42 postnatal mature spermatids occur. From day 56 postnatal on the seminiferous epithelium, as well as the

  11. Effect of methoxychlor on the antioxidant system in mitochondrial and microsome-rich fractions of rat testis.

    Science.gov (United States)

    Latchoumycandane, C; Mathur, P P

    2002-07-01

    Methoxychlor, an environmental contaminant, which is widely used as a pesticide in many countries, has been shown to induce reproductive abnormalities in male rats. The precise nature and mechanism of action of methoxychlor on the male reproductive system is not clear. In the present study, we have sought to investigate the induction of oxidative stress in the testis of rat after exposure to methoxychlor. Methoxychlor (1, 10, and 100 mg kg(-1) body weight per day) was administered orally to the rats for 45 days. After 24 h of the last treatment the animals were killed using anesthetic ether. The body weight of the animals administered with methoxychlor did not show any significant change. The weights of the testis, epididymis, seminal vesicles and ventral prostate decreased significantly in 100 mg dose but remained unchanged in 1 and 10 mg doses. Mitochondrial and microsome-rich fractions of the testis were obtained by the method of differential centrifugation. The activities of antioxidant enzymes such as superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase decreased significantly in the animals treated with methoxychlor in a dose-dependent manner in the mitochondrial and microsome-rich fractions of rat testis. The levels of hydrogen peroxide generation (H(2)O(2)) and lipid peroxidation increased in mitochondrial and microsome-rich fractions of the testis of the rats treated with methoxychlor. The results suggested that the low to medium doses of methoxychlor elicit depletion of antioxidant enzymes and concomitant increase in the levels of H(2)O(2) and lipid peroxidation differentially in mitochondrial and microsome-rich fractions of rat testis. In conclusion, the adverse effect of methoxychlor on male reproduction could be due to the induction of oxidative stress in testis.

  12. The effects of carvedilol on ischemia-reperfusion injury in the rat testis

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    B.S. Parlaktas

    2014-01-01

    Full Text Available Objective: To analyze the oxidative damage and histopathological alterations caused by ischemia-reperfusion (I/R injury and ameliorative effects of carvedilol (CVD in the rat testis. Materials and Methods: Twenty-one male rats were randomized into 3 groups as follows: Group I (n = 7; control (sham group, Group II (n = 7; I/R group, in which I/R injury was performed by torsing the left testis 720º clockwise for 2 hours and detorsing for 2 hours. Group III (n = 7; CVD treatment group; in addition to I/R process, one-dose of CVD was administered (2mg/kg, i.p 30 min. before detorsion. Levels of antioxidant enzymes, superoxide dismutase (SOD and glutathione peroxidase (GSH-Px and levels of malondialdehyde (MDA and protein carbonyl (PC were determined in testicular tissues and serum of rats. Testicular tissues were also examined histopathologically and Johnsen scores were determined. Results: Activities of SOD and GSH-Px in serum and testicular tissues were increased by I/R, but administration of CVD decreased these levels (p < 0.001 and p = 0.001. Significantly increased MDA levels in serum and testicular tissues were decreased by CVD treatment (p < 0.001 and p = 0.001. Concerning PC levels in serum and testicular tissues, there was no statistically significant difference between the groups (p = 0.989 and p = 0.428. There was not a statistically significant difference in terms of mean Johnsen scores between the groups (p = 0.161. Conclusions: Administration of CVD decreased oxidative damage biochemically in the rat testis caused by I/R injury, but histopathologically no change was observed between all of the groups.

  13. Preventive effect of zinc against cadmium-induced oxidative stress in the rat testis.

    Science.gov (United States)

    Amara, Salem; Abdelmelek, Hafedh; Garrel, Catherine; Guiraud, Pascale; Douki, Thierry; Ravanat, Jean-Luc; Favier, Alain; Sakly, Mohsen; Ben Rhouma, Khémais

    2008-04-01

    The aim of this study was to investigate the antioxidant role of zinc (Zn) in the Cd-exposed testes of Wistar rats. Subchronic exposure to Cd (CdCl(2), 40 mg/l, per os) for 30 days resulted in a significant reduction in growth rate (-11%) and relative weights of testes (-36%) and seminal vesicles (-80%). Treated rats displayed a decrease in testicular and plasma testosterone levels, respectively (-70%, Pspermatozoa motility (-35%, PZinc supplementation (ZnCl(2), 40 mg/l, per os) in the Cd-exposed rats restored the activities of GPx, CuZn-SOD, and Mn-SOD in the testes to the levels of the control group. Moreover, zinc administration was capable of reducing the elevated levels of malondialdehyde in the testis. Interestingly, zinc supplementation attenuated DNA oxidation induced by Cd in the gonad and restored the testosterone level and sperm count to the levels of the control group. Zinc administration minimized oxidative damage and reversed the impairment of spermatogenesis and testosterone production induced by Cd in the rat testis.

  14. The cloning and expression characterization of the centrosome protein genes family (centrin genes) in rat testis

    Institute of Scientific and Technical Information of China (English)

    SUN; Xiaodong(孙晓冬); GE; Yehua(葛晔华); MA; Jing(马静); YU; Zuoren(俞作仁); LI; Sai(李赛); WANG; Yongchao(王永潮); XUE; Shepu(薛社普); HAN; Daishu(韩代书)

    2002-01-01

    Centrins are members of the centrosome protein family, which is highly conserved during revolution. The homologous genes of centrin in many organisms had been cloned, but the sequences of the rat centrin genes were not reported yet in GenBank. We cloned the cDNA fragments of centrin-1, -2 and -3 from the rat testis by RT-PCR, and analyzed the homology of the deduced amino acid sequences. The expression characterization of centrin genes in rat spermatogenesis was carried out by semi-quantitative RT-PCR. The results show that the homology of the corresponding centrin proteins in human, mouse and rat is high. The expression of centrin-1 is testis-specific, spermatogenic cell-specific and developmental stage-related. Centrin-1 begins to be transcribed when the meiosis occurs, and its mRNA level reaches the peak in round spermatids. Centrin-2 and centrin-3 are highly expressed in spermatogonia and their mRNA level decreases markedly when meiosis occurs. These results suggest that centrin-1 may play roles in meiosis and spermiogenesis, and centrin-2 and centrin-3 may be related to mitosis.

  15. Location and Quantification of iNOS in Testis of Dahl Hypertensive Rats

    Institute of Scientific and Technical Information of China (English)

    Jing LIU; Rui-li LI; Huan-Ying ZHAO; Xiu-Ling YIN

    2004-01-01

    Objective To study the effect of hypertension on inducible isoform of nitrogen oxide syntheses (iNOS) expression and reproductive function in testes of Dahl hypertensive rats Method The iNOS expression in Dahl rat testes was localized and assayed semi-quan titatively by immunohistochemistry.Results iNOS was expressed and localized predominantly in the cytoplasm of Sertoli and Leydig cells in both normal and hypertensive rats. However, in the early stage of hypertension, the expression of iNOS was stronger in testes than that of the normal rats (P<0. 05). With the development, the staining intensity of iNOS decreased gradually in the late stage. Moreover, the level of testosterone decreased with the increase of blood pressure. But in vitro, there was no difference in the expression of iNOS between cultured Sertoli cells from normal rats and hypertensive rats.Conclusion High-salt food induced hypertension in Dahl rats, which was characterized by the high expression of iNOS in rat Sertoli and Leydig cells; excessive NO produced by iNOS reduced the level of testosterone in testicle artery, and may thus affect the reproductive function of rats testis.

  16. Hemorrhage Near Fetal Rat Bone: Preliminary Results

    Science.gov (United States)

    Bigelow, Timothy A.; Miller, Rita J.; Blue, James P.; O'Brien, William D.

    2006-05-01

    High-intensity ultrasound has shown potential in treating many ailments requiring noninvasive tissue necrosis. However, little work has been done on using ultrasound to ablate pathologies on or near the developing fetus. For example, Congenital Cystic Adenomatoid Malformation (cyst on lungs), Sacrococcygeal Teratoma (benign tumor on tail bone), and Twin-Twin Transfusion Syndrome (one twin pumps blood to other twin) are selected problems that will potentially benefit from noninvasive ultrasound treatments. Before these applications can be explored, potential ultrasound-induced bioeffects should be understood. Specifically, ultrasound-induced hemorrhage near the fetal rat skull was investigated. An f/1 spherically focused transducer (5.1-cm focal length) was used to expose the skull of 18- to 19-day-gestation exteriorized rat fetuses. The ultrasound pulse had a center frequency of 0.92 MHz and pulse duration of 9.6 μs. The fetuses were exposed to 1 of 4 exposure conditions (denoted A, B, C, and D) in addition to a sham exposure. Three of the exposures consisted of a peak compressional pressure of 10 MPa, a peak rarefactional pressure of 6.7 MPa, and pulse repetition frequencies of 100 Hz (A), 250 Hz (B), and 500 Hz (C), corresponding to time-average intensities of 1.9 W/cm2, 4.7 W/cm2, and 9.4 W/cm2, respectively. Exposure D consisted of a peak compressional pressure of 6.7 MPa, a peak rarefactional pressure of 5.0 MPa, and a PRF of 500 Hz corresponding to a time-average intensity of 4.6 W/cm2. Hemorrhage occurrence increased slightly with increasing time-average intensity (i.e., 11% for A, 28% for B, 31% for C, and 19% for D with a 9% occurrence when the fetuses were not exposed). The low overall occurrence of hemorrhaging may be attributed to fetal motion (observed in over half of the fetuses from the backscattered echo during the exposure). The mean hemorrhage sizes were 3.1 mm2 for A, 2.5 mm2 for B, 2.7 mm2 for C, and 5.1 mm2 for D. The larger lesions at D may

  17. Intermedin attenuates LPS-induced inflammation in the rat testis.

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    Lei Li

    Full Text Available First reported as a vasoactive peptide in the cardiovascular system, intermedin (IMD, also known as adrenomedullin 2 (ADM2, is a hormone with multiple potent roles, including its antioxidant action on the pulmonary, central nervous, cardiovascular and renal systems. Though IMD may play certain roles in trophoblast cell invasion, early embryonic development and cumulus cell-oocyte interaction, the role of IMD in the male reproductive system has yet to be investigated. This paper reports our findings on the gene expression of IMD, its receptor components and its protein localization in the testes. In a rat model, bacterial lippolysaccharide (LPS induced atypical orchitis, and LPS treatment upregulated the expression of IMD and one of its receptor component proteins, i.e. receptor activity modifying protein 2 (RAMP2. IMD decreased both plasma and testicular levels of reactive oxygen species (ROS production, attenuated the increase in the gene expression of the proinflammatory cytokines tumor necrosis factor alpha (TNFα, interleukin 6 (IL6 and interleukin 1 beta (IL1β, rescued spermatogenesis, and prevented the decrease in plasma testosterone levels caused by LPS. The restorative effect of IMD on steroidogenesis was also observed in hydrogen peroxide-treated rat primary Leydig cells culture. Our results indicate IMD plays an important protective role in spermatogenesis and steroidogenesis, suggesting therapeutic potential for IMD in pathological conditions such as orchitis.

  18. Activation of GPER-1 estradiol receptor downregulates production of testosterone in isolated rat Leydig cells and adult human testis.

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    Laurent Vaucher

    Full Text Available PURPOSE: Estradiol (E2 modulates testicular functions including steroidogenesis, but the mechanisms of E2 signaling in human testis are poorly understood. GPER-1 (GPR30, a G protein-coupled membrane receptor, mediates rapid genomic and non-genomic response to estrogens. The aim of this study was to evaluate GPER-1 expression in the testis, and its role in estradiol dependent regulation of steroidogenesis in isolated rat Leydig cells and human testis. MATERIALS AND METHODS: Isolated Leydig cells (LC from adult rats and human testicular tissue were used in this study. Expression and localization studies of GPER-1 were performed with qRT-PCR, immunofluorescence, immunohistochemistry and Western Blot. Luteinizing Hormone (LH -stimulated, isolated LC were incubated with estradiol, G-1 (GPER-1-selective agonist, and estrogen receptor antagonist ICI 182,780. Testosterone production was measured with radioimmunoassay. LC viability after incubation with G-1 was measured using 3-(4,5-dimethylthiazol-2-yl-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium, inner salt (MTS assay. RESULTS: GPER-1 mRNA is abundantly expressed in rat LC and human testis. Co-localization experiments showed high expression levels of GPER-1 protein in LC. E2-dependent activation of GPER-1 lowers testosterone production in isolated rats LCs and in human testis, with statistically and clinically significant drops in testosterone production by 20-30% as compared to estradiol-naïve LC. The exposure to G-1 does not affect viability of isolated LCs. CONCLUSIONS: Our results indicate that activation of GPER-1 lowers testosterone levels in the rat and human testis. The expression of GPER-1 in human testis, which lack ERα, makes it an exciting target for developing new agents affecting testosterone production in men.

  19. Molecular cloning and expression of a new gene, GON-SJTU1 in the rat testis

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    Tian Geng G

    2010-05-01

    Full Text Available Abstract Background Spermatogenesis is a complex process involving cell development, differentiation and apoptosis. This process is governed by a series of genes whose expressions are highly regulated. Male infertility can be attributed to multiple genetic defects or alterations that are related to spermatogenesis. The discovery, cloning and further functional study of genes related to spermatogenesis is of great importance to the elucidation of the molecular mechanism of spermatogenesis. It is also physiologically and pathologically significant to the therapy of male infertility. Methods GON-SJTU1 was identified and cloned from rat testis by cDNA library screening and 3'-and 5'-RACE. The products of GON-SJTU1 were assessed by Northern and Western blotting. The expression of GON-SJTU1 was also examined by In situ hybridization and immunohistochemistry. Results Here we identified and cloned a new gene, GON-SJTU1, with the biological process of spermatogenesis. GON-SJTU1 is highly expressed in the testis from day 1 to 15 and then decreased, suggesting that GON-SJTU1 might be a time-related gene and involved in the early stage of spermatogenesis. And the expression of GON-SJTU1 in the testis occurred in some male germ cells, particularly in gonocytes and spermatogonial stem cells. Conclusion GON-SJTU1 may play a role in the biological process of spermatogenesis.

  20. Survey of Growth Hormone Effects on Methotrexate Side Effects in Rat Testis

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    A. Khaki

    2007-10-01

    Full Text Available Introduction & Objectives: Methotrexate (MTX is a chemotherapeutic agent that used for the treatment of a variety of tumors and inflammatory diseases. The aim of this study was planed to see the role of human growth hormone (hGH on testis recovery after treatment with MTX in rat. Materials & Methods: In this experimental study the fifty male wistar rat were selected and randomly divided into five groups; control (n=10 and test (n=40. Hormone grope was received 0.3mg/kg hGH (IP for 28 consequence day, drug group was received 1mg/kg MTX (IP per week for four consequence week, protective group was received 0.3mg/kg hGH (IP for 28 consequence day plus1mg/kg MTX (IP per week for four consequence week and treatment group was received 1mg/kg MTX (IP per week for two consequence week with 0.3mg/kg hGH (IP for14 consequence day, however the control group just received vehicle (IP. In 14 and 28 day the testis tissue of rat in whole groups were removed and sperm was collected from epididymis then prepared for analysis. The statically analysis was ANOVA test. Results: This study was confirmed MTX had destructive effects in testis germinal cells and rate of spermatogenesis was decreased (P<0.05 as compared with control group, and HGh had treatment effects in degenerative seminiferous epithelium and improve spermatogenesis (P<0.05 as compared in other groups.Conclusion: Since in our study hGH had recovery effect on spermatogenesis cycle after treatment with MTX, and it can not have useful effect if only prescript in chemotherapy period than consequently hGH inducement is suitable for sperm health ability parameters after chemotherapy in patient.

  1. Protective effects of propolis on methotrexate-induced testis injury in rat.

    Science.gov (United States)

    Sönmez, Mehmet Fatih; Çilenk, Kübra Tuğçe; Karabulut, Derya; Ünalmış, Sunay; Deligönül, Erkan; Öztürk, İsmet; Kaymak, Emin

    2016-04-01

    Propolis is an adhesive substance which is collected and used by honeybees. Propolis is a potent antioxidant and a free radical scavenger. This study was designed to determine whether propolis could protect against dysfunction and oxidative stress induced by methotrexate-induced injury in rat testis. A total of 40 male Wistar albino rats were divided into four groups: group 1 was the untreated control. On the eighth day of the experiment, groups 2 and 3 received single intraperitoneal injections of methotrexate (MTX) at 20mg/kg. Groups 3 and 4 received 100mg/kg/day propolis (by oral gavage) for 15 days by the first day of the experimental protocol. Then the rats were decapitated under anesthesia, and their testes were removed. The histopathological and biochemical analysis along with apoptosis assessment of testis tissues were compared. Immunohistochemical analysis of Heat shock protein-70 (HSP-70) and Proliferating Cell Nuclear Antigen (PCNA) were performed. The phenolic characterization of propolis was performed by Liquid chromatography-mass spectrometry (LC-MS/MS). Methotrexate caused tended to increase in malondialdehyde level and in the number of apoptotic cells; it also caused a decrease in MSTD and JTBS, PCNA and HSP-70 expression and xanthine oxidase levels in group 2. Propolis prevented the rise in malondialdehyde, xanthine oxidase levels and HSP-70 expression and improved testicular morphology and JTBS. It was found that, methorexate gives rise to serious damage in the testes and propolis is a potent antioxidant agent in preventing testicular injury.

  2. Protective effects of estrogens and caloric restriction during aging on various rat testis parameters

    Institute of Scientific and Technical Information of China (English)

    Khaled Hamden; Dorothee Silandre; Christelle Delalande; Abdelfattah ElFek; Serge Carreau

    2008-01-01

    Aim: To investigate the effects of 17β-estradiol (E2), Peganum harmala extract (PHE) and caloric restriction (CR) on various testis parameters during aging. Methods: Twelve-month-old male rats were treated for 6 months with either E2 or PHE, or submitted to CR (40%). Results: Our results show that estrogens and CR are able to protect the male gonad by preventing the decrease of testosterone and E2 levels as well as the decrease of aromatase and estrogen receptor gene expressions. Indeed, E2, PHE and CR treatments induced an increase in the superoxide dismutase activities and decreased the activity of testicular enzymes: gamma-glutamyl transferase, alkaline phosphatase, lactate deshydrogenase as well as the aspartate and lactate transaminases in aged animals. In addition, the testicular catalase and gluthatione peroxidase activities were enhanced in E2, PHE and CR-treated rats compared to untreated animals at 18 months of age. Moreover, the positive effects of estradiol, PHE and CR were further supported by a lower level of lipid peroxidation. Recovery of spermatogenesis was recorded in treated rats. Conclusion: Besides a low caloric diet which is beneficial for spermatogenesis, a protective antioxydant role of estrogens is suggested. Estrogens delay testicular cell damage, which leads to functional senescence and, therefore, estrogens are helpful in protecting the reproductive functions from the adverse effects exerted by reactive oxygen species (ROS) produced in large quanti-ties in the aged testis.

  3. Pseudoephedrine induces sperm abnormalities, lower sperm counts and increased apoptosis in rat testis.

    Science.gov (United States)

    Nudmamud-Thanoi, Sutisa; Thanoi, Samur

    2012-08-01

    Pseudoephedrine, an over-the-counter drug, is commonly used for the treatments of asthma, nasal congestion, and obesity. Furthermore, it can be used as a psychostimulant drug if taken in large doses; however, there have been no reports on its effects on reproduction. The aim of this study was therefore to investigate the effects of pseudoephedrine administration on sperm morphology, sperm concentration and apoptotic activity in the rat testis. Rats were administered intraperitoneally (IP) with pseudoephedrine at 120 mg/kg for the acute group and 80 mg/kg, IP, once daily for 15 days for the chronic group, while a control group was treated with vehicle. The percentages of normal sperm morphology were significantly decreased in both acute and chronic groups when compared with controls while the total sperm count was significantly decreased in the acute group. Apoptotic activities were increased significantly in both pseudoephedrine-treated groups. The results indicate that pseudoephedrine can induce sperm abnormalities, decrease sperm numbers and increase apoptotic activity in the testis of rats if taken at high doses. The results of this study suggest that the users of pseudoephedrine in medical treatments need to be aware of its potential toxicity involving spermatogenesis.

  4. Rat fetal ventral mesencephalon grown as solid tissue cultures

    DEFF Research Database (Denmark)

    Höglinger, G U; Sautter, J; Meyer, Morten;

    1998-01-01

    Free-floating roller tube (FFRT) cultures of fetal rat and human nigral tissue are a means for tissue storage prior to grafting in experimental Parkinson's disease. In the present study, FFRT cultures prepared from embryonic-day-14 rat ventral mesencephalon were maintained for 4, 8, 12, or 16 days...

  5. Comparative study on glutathione transferases of rat brain and testis under the stress of phenobarbitol and β-methylcholanthrene

    Institute of Scientific and Technical Information of China (English)

    THYAGARAJU K.; HEMAVATHI B.; VASUNDHARA K.; RAO A.D.; DEVI K.N.

    2005-01-01

    A comparative study was made on the tissue specific expression of glutathione transferases (GST) in brain and testis after exposure of rat to phenobarbitol (PB) and 3-methylcholanthrene (MC). Glutathione transferases, a family of multifunctional proteins are involved in intracellular transport processes and in detoxication of electrophilic xenobiotics by catalyzing reactions such as conjugation, isomerization, reduction and thiolysis. On purification, the yield of GST proteins by affinity chromatography was 39% in testis and 32% in brain. The affinity purified testis GSTs were resolved by chromatofocusing into six anionic and four cationic isozymes, and in brain glutathione transferases were resolved into four anionic and three cationic isozymes, suggesting the presence of multiple isozymes with Yc, Yb, Y3 and Yδ in both of them. In testis and brain, these isozymes at identical pI values showed variable functions with a battery of substrates and the cationic isozymes of brain and testis showed identical properties in CHP (cumene hydroperoxide) at pH values of above 7.0. Substrate specificity studies and immunoblot analysis of testis and brain proteins revealed that they play a predominant role in the detoxication of phenobarbitol or 3-methylcholanthrene. Expression of the isozymes in testis and brain on exposure to PB and MC indicated elevated subunit variation. In both testis and brain, Yδ ofπclass was expressed on PB treatment and Yc of α class and Y3 of μ class was expressed in MC treated testis and only Yc was predominantly expressed in MC treated brain. Thus these subunits expression is considered as markers for carcinogenesis and specific to chemical toxicity under phenobarbitol and 13-methylcholanthrene stress.

  6. Comparative study on glutathione transferases of rat brain and testis under the stress of phenobarbitol and beta-methylcholanthrene.

    Science.gov (United States)

    Thyagaraju, K; Hemavathi, B; Vasundhara, K; Rao, A D; Devi, K N

    2005-08-01

    A comparative study was made on the tissue specific expression of glutathione transferases (GST) in brain and testis after exposure of rat to phenobarbitol (PB) and b-methylcholanthrene (MC). Glutathione transferases, a family of multifunctional proteins are involved in intracellular transport processes and in detoxication of electrophilic xenobiotics by catalyzing reactions such as conjugation, isomerization, reduction and thiolysis. On purification, the yield of GST proteins by affinity chromatography was 39% in testis and 32% in brain. The affinity purified testis GSTs were resolved by chromatofocusing into six anionic and four cationic isozymes, and in brain glutathione transferases were resolved into four anionic and three cationic isozymes, suggesting the presence of multiple isozymes with Yc, Yb, Ybeta and Ydelta in both of them. In testis and brain, these isozymes at identical pI values showed variable functions with a battery of substrates and the cationic isozymes of brain and testis showed identical properties in CHP (cumene hydroperoxide) at pH values of above 7.0. Substrate specificity studies and immunoblot analysis of testis and brain proteins revealed that they play a predominant role in the detoxication of phenobarbitol or beta-methylcholanthrene. Expression of the isozymes in testis and brain on exposure to PB and MC indicated elevated subunit variation. In both testis and brain, Ydelta of pi class was expressed on PB treatment and Yc of alpha class and Ybeta of mu class was expressed in MC treated testis and only Yc was predominantly expressed in MC treated brain. Thus these subunits expression is considered as markers for carcinogenesis and specific to chemical toxicity under phenobarbitol and beta-methylcholanthrene stress.

  7. Comparative study on glutathione transferases of rat brain and testis under the stress of phenobarbitol and β-methylcholanthrene*

    Science.gov (United States)

    Thyagaraju, K.; Hemavathi, B.; Vasundhara, K.; Rao, A.D.; Devi, K.N.

    2005-01-01

    A comparative study was made on the tissue specific expression of glutathione transferases (GST) in brain and testis after exposure of rat to phenobarbitol (PB) and β-methylcholanthrene (MC). Glutathione transferases, a family of multifunctional proteins are involved in intracellular transport processes and in detoxication of electrophilic xenobiotics by catalyzing reactions such as conjugation, isomerization, reduction and thiolysis. On purification, the yield of GST proteins by affinity chromatography was 39% in testis and 32% in brain. The affinity purified testis GSTs were resolved by chromatofocusing into six anionic and four cationic isozymes, and in brain glutathione transferases were resolved into four anionic and three cationic isozymes, suggesting the presence of multiple isozymes with Yc, Yb, Yβ and Yδ in both of them. In testis and brain, these isozymes at identical pI values showed variable functions with a battery of substrates and the cationic isozymes of brain and testis showed identical properties in CHP (cumene hydroperoxide) at pH values of above 7.0. Substrate specificity studies and immunoblot analysis of testis and brain proteins revealed that they play a predominant role in the detoxication of phenobarbitol or β-methylcholanthrene. Expression of the isozymes in testis and brain on exposure to PB and MC indicated elevated subunit variation. In both testis and brain, Yδ of π class was expressed on PB treatment and Yc of α class and Yβ of μ class was expressed in MC treated testis and only Yc was predominantly expressed in MC treated brain. Thus these subunits expression is considered as markers for carcinogenesis and specific to chemical toxicity under phenobarbitol and β-methylcholanthrene stress. PMID:16052709

  8. Evaluation of the effects of α-cypermethrin on fetal rat testicular steroidogenesis.

    Science.gov (United States)

    Saillenfait, Anne-Marie; Sabaté, Jean-Philippe; Denis, Flavien; Antoine, Guillaume; Robert, Alain; Roudot, Alain-Claude; Ndiaye, Dieynaba; Eljarrat, Ethel

    2017-09-01

    Pregnant Sprague-Dawley rats were administered the insecticide α-cypermethrin at doses of 0.1, 1, 5, or 10mg/kg/day, or di-isobutyl phthalate (DIBP) at 250mg/kg/day, by gavage, from gestation day (GD) 13 to 19. Testicular testosterone production and the expression of several key genes related to cholesterol and androgen synthesis and transport were assessed in GD 19 male fetuses. Dams treated with 10mg/kg/day of α-cypermethrin showed clinical signs of neurotoxicity and reduced body weight gain. α-Cypermethrin had no significant effect on post-implantation loss, fetal weight, incidence of male fetuses per litter, or anogenital distance of the male fetuses. In the fetal testes, mRNA expressions of HMG-CoA synthase and reductase, SRB1, StAR, P450scc, 3βHSD, P450 17A1, and 17βHSD were not affected by exposure to α-cypermethrin. Testosterone production by the fetal testis was significantly reduced at 5 and 10mg/kg/day of α-cypermethrin, although to a much smaller extent than in DIBP-exposed fetuses. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. The Effect of the Alcoholic Extract of Walnut on the Testis Tissue of Adult Male Rats

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    M Abedinzade

    2012-08-01

    Methods: In the present experimental study, forty adult male Wistar rats weighing 250-300 grams were divided into five groups. The control group did not receive any treatment. Normal saline was intraperitoneally injected to the control group. Experimental groups received three different doses of alcoholic extract of walnut: 10, 20 and 50 mg/ kg intraperitoneally/daily, respectively. The testes were removed from the abdomen and the tissue sections were studied. The gathered data were analyzed using One-way Analysis of variance and Tukey's range test. Results: Results indicated that walnut extract affect the development and maintenance of spermatogenesis to its final stages, and increased the number of sperms and interstitial cells in the testis. Alcoholic extract of walnut during the test instrument did not have much impact on the structure of the sperm tube tissue. Conclusion: The alcoholic extract of walnut led to the increased activity of the testis and interstitial cells, followed by an increase in sperm cells and reproductive activity of male rats.

  10. Levels of oxidative stress parameters and the protective effects of melatonin in psychosis model rat testis

    Institute of Scientific and Technical Information of China (English)

    Bekir S.Parlaktas; Birsen Ozyurt; Huseyin Ozyurt; Ayten T.Tunc; Ali Akbas

    2008-01-01

    Aim: To evaluate the effects of melatonin on antioxidant enzyme levels and histopathologic changes in dizocilpine (MK-801)-induced psychosis model rat testis. Methods: A total of 24 adult male Wistar-Albino rats were divided into three groups with 8 in each. Group Ⅰ was used as control. Rats in Group Ⅱ were injected with MK-801 (0.5 mg/kg body weight i.p. for 5 days). In addition to MK-801, melatonin (50 mg/kg body weight i.p. once a day for 5 days) was injected into the rats in Group Ⅲ. The testes were harvested bilaterally for biochemical and histopathological examinations. Antioxidant enzyme activities, malondialdehyde, protein carbonyl and nitric oxide (NO) levels in tes-ticular tissues were analyzed using spectrophotometric analysis methods. Histopathological examinations of the testes were also performed. Results: MK-801 induced testicular damage, which resulted in significant oxidative stress (OS) by increasing the levels of antioxidant enzymes. The malondialdehyde, protein carbonyl and NO levels were increased in testicular tissues of rats. Treatment with melatonin led to significant decrease in oxidative injury.Administration of melatonin also reduced the detrimental histopathologic effects caused by MK-801. Conclusion:The results of the present study showed that MK-801 cause OS in testicular tissues of rats and treatment with melatonin can reduce the harmful effects of MK-801.

  11. An investigation of the endocrine-disruptive effects of bisphenol a in human and rat fetal testes.

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    Millissia Ben Maamar

    Full Text Available Few studies have been undertaken to assess the possible effects of bisphenol A (BPA on the reproductive hormone balance in animals or humans with often contradictory results. We investigated possible direct endocrine disruption by BPA of the fetal testes of 2 rat strains (14.5-17.5 days post-coitum and humans (8-12 gestational weeks and under different culture conditions. BPA concentrations of 10(-8M and 10(-5M for 72 h reduced testosterone production by the Sprague-Dawley fetal rat testes, while only 10-5M suppressed it in the Wistar strain. The suppressive effects at 10-5M were seen as early as 24h and 48 h in both strains. BPA at 10(-7-10(-5M for 72 h suppressed the levels of fetal rat Leydig cell insulin-like factor 3 (INSL3. BPA exposure at 10(-8M, 10(-7M, and 10(-5M for 72 h inhibited testosterone production in fetal human testes. For the lowest doses, the effects observed occurred only when no gonadotrophin was added to the culture media and were associated with a poorly preserved testicular morphology. We concluded that (i BPA can display anti-androgenic effects both in rat and human fetal testes; (ii it is essential to ascertain that the divergent effects of endocrine disruptors between species in vitro do not result from the culture conditions used, and/or the rodent strain selected; (iii the optimization of each in vitro assay for a given species should be a major objective rather than the search of an hypothetical trans-species consensual model-system, as the organization of the testis is intrinsically different between mammalian species; (iv due to the uncertainty existing on the internal exposure of the human fetal testis to BPA, and the insufficient number of epidemiological studies on the endocrine disruptive effects of BPA, caution should be taken in the extrapolation of our present results to the human reproductive health after fetal exposure to BPA.

  12. Radiation-induced apoptosis in developing fetal rat cerebral cortex

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Woong Ki; Nam, Taek Keun; Lee, Min Cheol; Ahn, Sung Ja; Song, Ju Young; Park, Seung Jin; Nah, Byung Sik [College of Medicine, Chonnam National Univ., Gwangju (Korea, Republic of)

    2003-09-01

    The study was performed to investigate apoptosis by radiation in the developing fetal rat brain. Fetal brains were irradiated in utero between the 17th and 19th days of fetal life(E17-19) by linear accelerator. A dose of irradiation ranging from 1 Gy to 4 Gy was used to evaluate dose dependency. To test time dependency the rats were irradiated with 2 Gy and then the fetal brain specimens were removed at variable time course; 1, 3, 6, 12 and 24 hours after the onset of irradiation. Immunohistochemical staining using in situ TdT-mediated dUTP nick end labelling (TUNEL) technique was used for apoptotic cells. The cerebral cortex, including three zones of cortical zone (CZ), intermediate zone (IZ), and ventricular zone (VZ), was examined. TUNEL positive cells revealed typical features of apoptotic cells under light microscope in the fetal rat cerebral cortex. Apoptotic cells were not found in the cerebral cortex of non-irradiated fetal rats, but did appear in the entire cerebral cortex after 1 Gy irradiation, and were more extensive at the ventricular and intermediate zones than at the cortical zone. The extent of apoptosis was increased with increasing doses of radiation. Apoptosis reached the peak at 6 hours after the onset of 2 Gy irradiation and persisted until 24 hours. Typical morphologic features of apoptosis by irradiation were observed in the developing fetal rat cerebral cortex. It was more extensive at the ventricular and intermediate zones than at the cortical zone, which suggested that stem cells or early differentiating cells are more radiosensitive than differentiated cells of the cortical zone.

  13. Effect of sildenafil citrate (Viagra) and ethanol on the Albino rat testis: a scanning electron microscopic approach.

    Science.gov (United States)

    Sivasankaran, T G; Udayakumar, R; Elanchezhiyan, C; Sabhanayakam, Selvi

    2008-02-01

    The effects of sildenafil citrate with ethanol on the rat testis was studied using scanning electron microscopy. Male Albino rats were divided into 8 groups, each being treated for a maximum of 45 days as follows. In the 4 short-term treatment groups, control rats were administered normal saline orally, whereas experimental animals were fed sildenafil citrate (Viagra) 1 microg/g with 18% ethanol (5 g/kg body weight), which was given orally as a single dose. After 1, 2.5, 4 and 24h the rats were killed. In the 4 long-term treatment groups, daily continuous doses of drug and ethanol with a single dosage were given for 15, 30 and 45 days and the animals killed 4h after the last dosage. Changes in the testis were compared with the normal healthy rat testis. The use of a scanning electron microscope for evaluation of the changes in the testis is more suitable for observation of the surface and morphological shapes of the tissue structures.

  14. Antioxidant and protective effects of Royal jelly on histopathological changes in testis of diabetic rats

    Science.gov (United States)

    Ghanbari, Elham; Nejati, Vahid; Khazaei, Mozafar

    2016-01-01

    Background: Diabetes is the most common endocrine disease. It has adverse effects on male reproductive function. Royal Jelly (RJ) has antioxidant and anti-diabetic effects and show protective effects against diabetes. Objective: This study was conducted to evaluate the effect of RJ on histopathological alterations of the testicular tissue in streptozotocin (STZ)-induced diabetic rats. Materials and Methods: In this experimental study, 28 adult Wistar rats were randomly divided into control (C), royal jelly (R), diabetic (D) and RJ-treated diabetic (D+R) groups. Diabetes was induced by a single intraperitoneal injection of STZ at 50 mg/kg body weight (BW). The rats from the R and D+R groups received daily RJ (100 mg/kg BW) for 6 wks orally. Hematoxylin-Eosin staining was used to analyze histopathological changes including: tunica albuginea thickness (TAT), seminiferous tubules diameter (STsD), Johnsen’s score, tubular differentiation index (TDI), spermiogenesis index (SPI), Sertoli cell index (SCI), meiotic index (MI), and mononuclear immune cells (MICs) in testes. The antioxidant status was examined by evaluating testicular levels of ferric reducing antioxidant power (FRAP) and catalase (CAT) activity. Results: Histological results of the testis from diabetic rats showed significant decrease in STsD, Johnsen’s score, TDI, SPI, SCI and MI, and significant increase in TAT and MICs, while administration of RJ significantly reverted these changes (p<0.05). RJ treatment markedly increased activity of CAT and FRAP. There were significant differences in FRAP levels among C (13.0±0.5), RJ (13.4±0.3), D (7.8±0.6) and D+R (12.4±0.7) groups (p<0.05). Conclusion: RJ improved diabetes-induced impairment in testis, probably through its antioxidant property. PMID:27679827

  15. Maternal Baicalin Treatment Increases Fetal Lung Surfactant Phospholipids in Rats

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    Chung-Ming Chen

    2011-01-01

    Full Text Available Baicalin is a flavonoid compound purified from the medicinal plant Scutellaria baicalensis Georgi and has been reported to stimulate surfactant protein (SP-A gene expression in human lung epithelial cell lines (H441. The aims of this study were to determine whether maternal baicalin treatment could increase lung surfactant production and induce lung maturation in fetal rats. This study was performed with timed pregnant Sprague-Dawley rats. One-day baicalin group mothers were injected intraperitoneally with baicalin (5 mg/kg/day on Day 18 of gestation. Two-day baicalin group mothers were injected intraperitoneally with baicalin (5 mg/kg/day on Days 17 and 18 of gestation. Control group mothers were injected with vehicle alone on Day 18 of gestation. On Day 19 of gestation, fetuses were delivered by cesarean section. Maternal treatment with 2-day baicalin significantly increased saturated phospholipid when compared with control group and total phospholipid in fetal lung tissue when compared with control and 1-day baicalin groups. Antenatal treatment with 2-day baicalin significantly increased maternal growth hormone when compared with control group. Fetal lung SP-A mRNA expression and maternal serum corticosterone levels were comparable among the three experimental groups. Maternal baicalin treatment increases pulmonary surfactant phospholipids of fetal rat lungs and the improvement was associated with increased maternal serum growth hormone. These results suggest that antenatal baicalin treatment might accelerate fetal rat lung maturation.

  16. NGF and BDNF long-term variations in the thyroid, testis and adrenal glands of a mouse model of fetal alcohol spectrum disorders

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    Mauro Ceccanti

    2013-12-01

    Full Text Available OBJECTIVES: Fetal Alcohol Spectrum Disorders (FASD due to prenatal ethanol consumption may induce long-lasting changes to the newborns affecting also the endocrine system and the nerve growth factor (NGF and brain derived neurotrophic factor (BDNF signaling. Thus the aim of this study was to investigate in the thyroid, testis and adrenal glands of a FASD mouse model the long-lasting effects of ethanol exposure during pregnancy and lactation on NGF and BDNF and their main receptors, TrkA and TrkB, including their phosphorylated patterns. METHODS: We used aged male CD-1 mice early exposed to ethanol solution or red wine at same ethanol concentration (11% vol. RESULTS We found elevations in NGF and BDNF in the thyroid of aged mice exposed to ethanol solution only but not in the red wine group. In the testis NGF resulted to be increased only in the ethanol solution group. In the adrenal glands data showed an elevation in NGF in both the ethanol solution group and red wine. No changes in TrkA, TrkB, phospho-TrkA and phospho-TrkB were revealed in all tissues examined. CONCLUSIONS Early administration of ethanol may induce long-lasting changes in the mouse thyroid, testis and adrenal glands at NGF and BDNF levels.

  17. The Effects of Hydroalcoholic Extract of Matricaria Recutita on the Hormonal Pituitary-Testis Axis and Testis Tissue Changes of Mature Male Rats

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    Laili Hatami

    2013-06-01

    Full Text Available Background & Objectives: Matricaria recutita is one of the most ancient and well- known medicinal plants, and its role in the treatment of a wide range of diseases has been studied . The purpose of this study was to investigate the effect of Matricaria recutita on spermatogenesis and the pituitary-gonadal axis in male adult rats.   Materials & Methods: In this experimental study, the animals were divided into two groups: the control group, which received 1 ml of distilled water orally, and the experimental group, which received 100 mg/kg of Matricaria recutita extract via gavage feeding once daily for an 8-week period. After the treatment period, several fertility indices such as the weight of the reproductive organs, sperm count, sperm motility and vitality, and testis histological changes as well as blood serum levels of testosterone, estrogen, FSH, and LH were measured.   Results: Our statistical analysis showed a significant increase in the weight of the reproductive organs, sperm count, and blood testosterone in the group which received 100 mg/kg of Matricaria recutita hydroalcholic extract .   Conclusion: The results of this study demonstrated that hydroalcholic extract of Matricaria recutita could increase the function of the hormonal pituitary-testis axis and spermatogenesis in male rats.  

  18. Effects of dietary selenium (SE) on morphology of testis and cauda epididymis in rats.

    Science.gov (United States)

    Kaur, R; Kaur, K

    2000-07-01

    Selenium is an essential micronutrient for animals. To determine whether its excess in diet induces morphological changes within the male reproductive system, a detailed qualitative and quantitative evaluation of the changes in the histology of the testis and cauda epididymis was undertaken in male rats. Adult male albino rats were fed 6 and 8 ppm Se in diet for 6 and 9 weeks. Each male consuming 6 ppm Se was mated with two untreated females, their offsprings were allowed to mature upto 12 weeks of age. The testes and cauda epididymes of male rats were prepared for light microscopy. Excess of dietary Se caused dose-time-dependent reduction in body weight and reproductive organ weights but increase in number of morphologically abnormal spermatozoa. Histopathological studies of the testes and cauda epididymis have revealed that Se-rich diets cause dose-time-dependent reduction in tubular diameter, epithelial height, number of spermatogenic cells and disintegration of cellular associations in the seminiferous tubules of testes along with reduction in the diameter of cauda epididymal tubules and pseudostratification of their epithelial lining. Progeny (feeding on normal diet) of paternally treated rats has shown retarded growth.

  19. Effects of estradiol and methoxychlor on Leydig cell regeneration in the adult rat testis.

    Science.gov (United States)

    Chen, Bingbing; Chen, Dongxin; Jiang, Zheli; Li, Jingyang; Liu, Shiwen; Dong, Yaoyao; Yao, Wenwen; Akingbemi, Benson; Ge, Renshan; Li, Xiaokun

    2014-05-06

    The objective of the present study is to determine whether methoxychlor (MXC) exposure in adulthood affects rat Leydig cell regeneration and to compare its effects with estradiol (E2). Adult 90-day-old male Sprague-Dawley rats received ethane dimethane sulfonate (EDS) to eliminate the adult Leydig cell population. Subsequently, rats were randomly assigned to four groups and gavaged with corn oil (control), 0.25 mg/kg E2 and 10 or 100 mg/kg MXC daily from days 5 to 30 post-EDS treatment. The results showed that MXC and E2 reduced serum testosterone levels on day 58 post-EDS treatment. qPCR showed Hsd17b3 mRNA levels were downregulated 7-15 fold by E2 and MXC, indicating that development of the new population of Leydig cells was arrested at the earlier stage. This observation was supported by the results of histochemical staining, which demonstrated that Leydig cells in MXC-treated testis on day 58 post-EDS treatment were mostly progenitor Leydig cells. However, Pdgfb mRNA levels were downregulated, while Lif transcript levels were increased by MXC. In contrast, E2 did not affect gene expression for these growth factors. In conclusion, our findings indicated that both MXC and E2 delayed rat Leydig cell regeneration in the EDS-treated model, presumably acting by different mechanisms.

  20. Effects of Estradiol and Methoxychlor on Leydig Cell Regeneration in the Adult Rat Testis

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    Bingbing Chen

    2014-05-01

    Full Text Available The objective of the present study is to determine whether methoxychlor (MXC exposure in adulthood affects rat Leydig cell regeneration and to compare its effects with estradiol (E2. Adult 90-day-old male Sprague-Dawley rats received ethane dimethane sulfonate (EDS to eliminate the adult Leydig cell population. Subsequently, rats were randomly assigned to four groups and gavaged with corn oil (control, 0.25 mg/kg E2 and 10 or 100 mg/kg MXC daily from days 5 to 30 post-EDS treatment. The results showed that MXC and E2 reduced serum testosterone levels on day 58 post-EDS treatment. qPCR showed Hsd17b3 mRNA levels were downregulated 7–15 fold by E2 and MXC, indicating that development of the new population of Leydig cells was arrested at the earlier stage. This observation was supported by the results of histochemical staining, which demonstrated that Leydig cells in MXC-treated testis on day 58 post-EDS treatment were mostly progenitor Leydig cells. However, Pdgfb mRNA levels were downregulated, while Lif transcript levels were increased by MXC. In contrast, E2 did not affect gene expression for these growth factors. In conclusion, our findings indicated that both MXC and E2 delayed rat Leydig cell regeneration in the EDS-treated model, presumably acting by different mechanisms.

  1. Protective effects of acupuncture and electroacupuncture on oxidative stress and inflammation due to testis torsion/detorsion in rats.

    OpenAIRE

    PorfÃrio Cezar Passos Acioli

    2014-01-01

    The efects of acupuncture (Ac) and Electroacupuncture (EAc) were evaluated using an experimental rat model of ischemia/reperfusion (IR) of the testis. In Traditonal Chinese Medicine, these forms of therapies are used in the promotion of organic equilbrium, through stimulation of specifc neurotransmiters producing nerve pathways, resulting in a analgesic and anti-nflammatory autonomic regulatory. response. In the study, 30 male Wistar rats, 279.6g average weight (230-30 g) were ...

  2. The effect of vitamin E and L-carnitine against methotrexate-induced injury in rat testis

    OpenAIRE

    YÜNCÜ, MEHMET; BÜKÜCÜ, NEZAHAT; BAYAT, NURAY; SENCAR, LEMAN; Tarakçioğlu, Mehmet

    2015-01-01

    Background/aim: Methotrexate (MTX), used commonly as an antimetabolite drug in cancer therapy, leads to acute toxic side effects in tissues or organs containing rapidly dividing cells, such as bone marrow, gastrointestinal mucosa, and seminiferous tubules. In this study, we investigated the protective effects of vitamin E and L-carnitine against MTX-induced injury in rat testis. Materials and methods: Rats were divided into 4 groups, including the control group. The study took 17 days and th...

  3. ACTIONS OF THE ENDOCRINE DISRUPTOR METHOXYCHLOR AND ITS ESTROGENIC METABOLITE ON IN VITRO EMBRYONIC RAT SEMINIFEROUS CORD FORMATION AND PERINATAL TESTIS GROWTH. (R827405)

    Science.gov (United States)

    AbstractThe current study examines the actions of methoxychlor and its estrogenic metabolite, 2, 2-bis-(p-hydroxyphenyl)-1, 1, 1-trichloroethane (HPTE), on seminiferous cord formation and growth of the developing rat testis. The developing testis in the embryonic and ...

  4. The lack of histological changes of CDMA cellular phone-based radio frequency on rat testis.

    Science.gov (United States)

    Lee, Hae-June; Pack, Jeong-Ki; Kim, Tae-Hong; Kim, Nam; Choi, Soo-Yong; Lee, Jae-Seon; Kim, Sung-Ho; Lee, Yun-Sil

    2010-10-01

    We examined the histological changes by radiofrequency (RF) fields on rat testis, specifically with respect to sensitive processes such as spermatogenesis. Male rats were exposed to 848.5 MHz RF for 12 weeks. The RF exposure schedule consisted of two 45-min RF exposure periods, separated by a 15-min interval. The whole-body average specific absorption rate (SAR) of RF was 2.0 W/kg. We then investigated correlates of testicular function such as sperm counts in the cauda epididymis, malondialdehyde concentrations in the testes and epididymis, frequency of spermatogenesis stages, germ cell counts, and appearance of apoptotic cells in the testes. We also performed p53, bcl-2, caspase 3, p21, and PARP immunoblotting of the testes in sham- and RF-exposed animals. Based on these results, we concluded that subchronic exposure to 848.5 MHz with 2.0 W/kg SAR RF did not have any observable adverse effects on rat spermatogenesis.

  5. Proteomic analysis of 3-MCPD and 3-MCPD dipalmitate toxicity in rat testis.

    Science.gov (United States)

    Sawada, Stefanie; Oberemm, Axel; Buhrke, Thorsten; Meckert, Christine; Rozycki, Christel; Braeuning, Albert; Lampen, Alfonso

    2015-09-01

    Thermal treatment of foodstuff containing fats and salt promotes the formation of 3-chloropropane-1,2-diol (3-MCPD) and its fatty acid esters. 3-MCPD-exposed rats develop testicular lesions and Leydig cell tumors. 3-MCPD and 3-MCPD ester toxicity is thought to be caused by 3-MCPD and its metabolites, since 3-MCPD esters are hydrolyzed in the gut. Inhibition of glycolysis is one of the few known molecular mechanisms of 3-MCPD toxicity. To obtain deeper insight into this process, a comparative proteomic approach was chosen, based on a 28-days repeated-dose feeding study with male Wistar rats. Animals received equimolar doses of 3-MCPD or 3-MCPD dipalmitate. A lower dose of 3-MCPD dipalmitate was also administered. Absence of histopathological changes supported an analysis of early cellular disturbance. Testes were analyzed by two-dimensional gel electrophoresis followed by mass-spectrometric protein identification. Data provide a comprehensive overview of proteomic changes induced by 3-MCPD and 3-MCPD dipalmitate in rat testis in an early phase of organ impairment. Results are compatible with known 3-MCPD effects on reproductive function, substantially extend our knowledge about cellular responses to 3-MCPD and support the hypothesis that toxicity of 3-MCPD and 3-MCPD esters is mediated via common effectors. DJ-1 was identified as a candidate marker for 3-MCPD exposure.

  6. MnSOD expression inhibited by electromagnetic pulse radiation in the rat testis.

    Science.gov (United States)

    Zeng, LiHua; Ji, XiTuan; Zhang, YanJun; Miao, Xia; Zou, ChangXu; Lang, HaiYang; Zhang, Jie; Li, YuRong; Wang, XiaoWu; Qi, HongXing; Ren, DongQin; Guo, GuoZhen

    2011-12-01

    Male Sprague Dawley rats were exposed to EMP irradiation of 100 kV/m peak-to-peak e-field intensity and different numbers of pulses. Rat sperm samples were prepared for analysis of sperm qualities; Testes were assessed by transmission electron microscopy and serum hormone concentrations were examined by radioimmunoassay; Enzymatic activities of Total-superoxide dismutase(T-SOD) and manganese-superoxide dismutase (MnSOD), the mRNA levels of MnSOD and cuprozinc-superoxide dismutase (CuZnSOD), and the density of malondialdehyde (MDA) were also determined. EMP irradiation did not affect spermatozoon morphology, micronucleus formation rate, sperm number or viability, but the acrosin reaction rate decreased at 24 h and 48 h and recovered by 72 h after irradiation as compared to the controls. The ultrastructure of rat testis displayed more serious damage at 24 h than at other time points (6 h, 12 h, 48 h). Serum levels of luteotrophic hormone (LH) and testosterone (T) were elevated in irradiated rats as compared to controls. After irradiation, enzymatic activities of T-SOD and MnSOD were reduced by 24 h, consistent with the changes observed in MnSOD mRNA expression; MDA content increased at 6 h in turn. These studies have quantified the morphological damage and dysfunction in the rat reproductive system induced by EMP. The mechanism of EMP induced damage may be associated with the inhibition of MnSOD expression.

  7. Role of ghrelin on testosterone secretion and the mRNA expression of androgen receptors in adult rat testis.

    Science.gov (United States)

    Wang, Lin; Fang, Fugui; Li, Yunsheng; Zhang, Yunhai; Pu, Yong; Zhang, XiaoYong

    2011-06-01

    The present study was designed to determine the effects of ghrelin on in vivo and in vitro secretion of testosterone (T) and the expression of androgen receptor (AR) mRNA in the adult rat testis. The distribution of growth hormone secretagogue receptors (GHS-R(1a)) in the testis was also investigated. GHS-R(1a) immunoreactivity presented mainly in Sertoli and Leydig cells, primary spermatocytes, and secondary spermatocytes. Adult rats that were intracerebroventricularly (i.c.v.) administrated different dosages (1 nmol and 3 nmol) of ghrelin could significantly inhibit the secretion of T. The experession of AR mRNA in the testis was also notably reduced with 3 nmol ghrelin. Additionaly, in vitro exposure of the Leydig cells to increasing concentrations of ghrelin resulted in no obvious changes of T secretion in the culture media and AR mRNA expression of Leydig cells. Overall, our data demonstrate that the i.c.v. injection of ghrelin plays a physiological role in T secretion and AR mRNA expression in the testis, further confirming the reproductive role of ghrelin.

  8. Induction of oxidative stress in the rat testis after short-term exposure to the organochlorine pesticide methoxychlor.

    Science.gov (United States)

    Latchoumycandane, C; Mathur, P P

    2002-12-01

    Methoxychlor is one of the environmental contaminants that has been shown to induce reproductive abnormalities in male rats. The mechanism of action of methoxychlor on the male reproductive system remains unclear. In the present study we have sought to investigate whether short-term administration of methoxychlor induces oxidative stress in the testis of adult rats. Methoxychlor (50, 100, or 200 mg/kg body weight per day) was administered orally for 1, 4, or 7 days. The animals were killed using anesthetic ether on the day following the last dosing. The weights of epididymides, seminal vesicles, and ventral prostate decreased after 50, 100, or 200 mg/kg per day for 7 days but remained unchanged after 1 and 4 days of treatment. The production of superoxide anion and hydrogen peroxide increased in the animals that received methoxychlor for 4 and 7 days. The activities of the antioxidant enzymes superoxide dismutase, catalase, glutathione reductase and glutathione peroxidase decreased, while the level of lipid peroxidation increased in the testis after 4 or 7 days of treatment. The results indicated that short-term exposure to methoxychlor induces oxidative stress in the testis by decreasing antioxidant enzymes and increasing lipid peroxidation, possibly by inducing reactive oxygen species. In conclusion, the adverse effect of methoxychlor on the male reproduction could be due to induction of oxidative stress in testis.

  9. Di(n-butyl phthalate has no effect on the rat prepubertal testis despite its estrogenic activity in vitro

    Directory of Open Access Journals (Sweden)

    Jerzy Długoński

    2012-01-01

    Full Text Available The aim of this study was to assess the impact of di(n-butyl phthalate (DBP on the rat’s prepubertal testis. Male Wistar rats were given daily subcutaneous injections with DBP (20 or 200 μg or a vehicle from the 5th to the 15th postnatal day (pd. On the 16th pd, the rats were euthanized, and the testes were dissected, weighed, and paraffin embedded. The blood was collected to determine the serum levels of testosterone (T, estradiol (E and FSH. The following parameters were assessed in the testis sections: diameter and length of seminiferous tubules (st, numbers of spermatogonia A + intermediate + B (A/In/B, preleptotene spermatocytes (PL, leptotene + zygotene + pachytene spermatocytes (L/Z/PA and Sertoli cells per testis, percentage of st containing gonocytes or pachytene spermatocytes or lumen. An estrogenicity in vitro test was performed by means of a transgenic yeast strain expressing human estrogen receptor alpha. At both doses, DBP had no influence on testis and seminal vesicle weight, st diameter and length, number of germ and Sertoli cells per testis, percentage of st containing gonocytes or pachytene spermatocytes or lumen. DBP did not change E, T or FSH serum levels. The in vitro yeast screen showed that DBP was a weak estrogenic compound, approximately six to seven orders of magnitude less potent than 17β-estradiol. In conclusion, exposure of a rat to DBP in doses 100 or 1,000-fold higher than a Tolerable Daily Intake for humans had no effect on its testicular development. (Folia Histochemica et Cytobiologica 2011; Vol. 49, No. 4, pp. 685–689

  10. Comparative study of the effects of gentamicin, neomycin, streptomycin and ofloxacin antibiotics on sperm parameters and testis apoptosis in rats.

    Science.gov (United States)

    Khaki, Arash; Novin, Marefat Ghaffari; Khaki, Amir Afshin; Nouri, Mohammad; Sanati, Ehsan; Nikmanesh, Mahdad

    2008-07-01

    The aim of this study was to investigate the comparative effects of aminoglycosides and fluoroquinolones on testis apoptosis and sperm parameters in rats. Fifty male Wistar rats were randomly divided into control (n = 10) and experimental (n = 40) groups. The experimental groups subdivided into four groups often. Each received 5 mg kg(-1) (IP) gentamicin, 50 mg kg(-1) (IP) neomycin, 40 mg kg(-1) (IP) streptomycin and 72 mg kg(-1) (IP) ofloxacin daily for 14 days, respectively; however, the control group just received vehicle (IP). In the fourteenth day, rats were killed and sperm analyzed for sperm parameters. Testis tissues were also prepared for TUNEL assay for detection of apoptosis. There was a significant decrease in sperm count, viability and motility in all of experimental groups when compared with control group. Although in streptomycin group these parameters were less decreased than in the other experimental groups. The apoptotic cells were significantly increased in all experimental groups when compared with those seen in the controlled group. Gentamicin, neomycin and streptomycin and ofloxacin have negative effects on sperm parameters and testis apoptosis in rats. However, these side effects are less seen in the streptomycin group. Therefore, it is recommended that usage of this drug have fewer side effects on male fertility.

  11. Taurine concentrations in fetal, neonatal and pregnant rats.

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    Akahori,Shuichiro

    1986-04-01

    Full Text Available The concentrations of taurine in the fetal and neonatal organs, and the maternal organs, plasma and urine of rats between the 15th day of gestation and the 21st day after birth were determined using an automatic amino acid analyzer. In the fetal liver and brain and in the placenta, the taurine concentration was the highest of all ninhydrin positive compounds. In the fetal liver and placenta, the concentrations of taurine increased significantly with the gestational days. Concentrations of taurine in the brain were much higher in the fetus and neonate than that in the adult. Moreover, the total amount of taurine per fetus increased markedly after the 15th day of gestation, and near term, reached almost the same amount as in the adult rat liver. In contrast to this, a significant decrease was observed in the taurine concentration in the maternal liver and muscle near term. The concentration of taurine in the urine of pregnant rats decreased near term, but in the plasma of pregnant rats the concentration of taurine did not change during pregnancy.

  12. Integrated proteomics and metabolomics analysis of rat testis: Mechanism of arsenic-induced male reproductive toxicity.

    Science.gov (United States)

    Huang, Qingyu; Luo, Lianzhong; Alamdar, Ambreen; Zhang, Jie; Liu, Liangpo; Tian, Meiping; Eqani, Syed Ali Musstjab Akber Shah; Shen, Heqing

    2016-09-02

    Arsenic is a widespread metalloid in environment, whose exposure has been associated with a broad spectrum of toxic effects. However, a global view of arsenic-induced male reproductive toxicity is still lack, and the underlying mechanisms remain largely unclear. Our results revealed that arsenic exposure decreased testosterone level and reduced sperm quality in rats. By conducting an integrated proteomics and metabolomics analysis, the present study aims to investigate the global influence of arsenic exposure on the proteome and metabolome in rat testis. The abundance of 70 proteins (36 up-regulated and 34 down-regulated) and 13 metabolites (8 increased and 5 decreased) were found to be significantly altered by arsenic treatment. Among these, 19 proteins and 2 metabolites were specifically related to male reproductive system development and function, including spermatogenesis, sperm function and fertilization, fertility, internal genitalia development, and mating behavior. It is further proposed that arsenic mainly impaired spermatogenesis and fertilization via aberrant modulation of these male reproduction-related proteins and metabolites, which may be mediated by the ERK/AKT/NF-κB-dependent signaling pathway. Overall, these findings will aid our understanding of the mechanisms responsible for arsenic-induced male reproductive toxicity, and from such studies useful biomarkers indicative of arsenic exposure could be discovered.

  13. Integrated proteomics and metabolomics analysis of rat testis: Mechanism of arsenic-induced male reproductive toxicity

    Science.gov (United States)

    Huang, Qingyu; Luo, Lianzhong; Alamdar, Ambreen; Zhang, Jie; Liu, Liangpo; Tian, Meiping; Eqani, Syed Ali Musstjab Akber Shah; Shen, Heqing

    2016-09-01

    Arsenic is a widespread metalloid in environment, whose exposure has been associated with a broad spectrum of toxic effects. However, a global view of arsenic-induced male reproductive toxicity is still lack, and the underlying mechanisms remain largely unclear. Our results revealed that arsenic exposure decreased testosterone level and reduced sperm quality in rats. By conducting an integrated proteomics and metabolomics analysis, the present study aims to investigate the global influence of arsenic exposure on the proteome and metabolome in rat testis. The abundance of 70 proteins (36 up-regulated and 34 down-regulated) and 13 metabolites (8 increased and 5 decreased) were found to be significantly altered by arsenic treatment. Among these, 19 proteins and 2 metabolites were specifically related to male reproductive system development and function, including spermatogenesis, sperm function and fertilization, fertility, internal genitalia development, and mating behavior. It is further proposed that arsenic mainly impaired spermatogenesis and fertilization via aberrant modulation of these male reproduction-related proteins and metabolites, which may be mediated by the ERK/AKT/NF-κB-dependent signaling pathway. Overall, these findings will aid our understanding of the mechanisms responsible for arsenic-induced male reproductive toxicity, and from such studies useful biomarkers indicative of arsenic exposure could be discovered.

  14. Structural Changes of the Testis and Changes in Semen Quality Parameters Caused by Intraperitoneal and Peroral Administration of Selenium in Rats

    OpenAIRE

    Michal Cabaj; Róbert Toman; Mária Adamkovičová; Peter Massányi; Svätoslav Hluchý; Norbert Lukáč; Jozef Golian

    2012-01-01

    The aim of this study was to find the structural changes in the testis and semen quality parameters of rat after a singleintraperitoneal and repeated peroral selenium administration. Rats were killed 36 hours following the intraperitonealadministration of selenium selenite (2 mg.kg-1 b.w.; 98% purity) and after 90 days of the peroral repeatedadministration of selenium in drinking water (5 mg.l-1). Testis samples were evaluated by histological andmorphometrical methods in light microscopy. Eva...

  15. Streptozotocin diabetes and insulin resistance impairment of spermatogenesis in adult rat testis: central vs. local mechanism.

    Science.gov (United States)

    Arikawe, A P; Oyerinde, A; Olatunji-Bello, I I; Obika, L F O

    2012-12-18

    Mammalian reproduction is dynamically regulated by the pituitary gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH). These hormones are synthesized in the pituitary gland following stimulation by the gonadotropin-releasing hormone (GnRH) and act by stimulating steroid production and gametogenesis in both males and females. Male adult Sprague-Dawley rats (120 - 140 g) were randomly divided into 7 groups. Group 1 > Control group; fed on normal rat pellets. Group 2 > Streptozotocin group; received a single dose IP injection of streptozotocin 45 mg/kg BW in Na+ citrate buffer pH 4.5. Group 3 > Streptozotocin-insulin treated group; received a single dose IP injection of streptozotocin as in group 2 above and treated with insulin sub-cutaneously. Group 4 > Streptozotocin-ginger treated group; received a single dose IP injection of streptozotocin as in group 2 above and treated with 500 mg/Kg Ginger extract orally. Group 5 > Insulin resistant group; fed ad libitum on a special diet containing 25% fructose mixed with 75% normal rat chow (w/w). Group 6 > Insulin resistant-pioglitazone treated group; fed ad libitum on a special diet as in group 5 above and treated with Pioglitazone 15 mg/kg orally. Group 7 > Insulin resistant-ginger treated group; fed ad libitum on a special diet as in group 4 above, and also treated with 500 mg/Kg Ginger extract orally. Hormonal and tissue biochemistry analyses revealed that both central and local mechanisms are implicated in the impairment of spermatogenesis by diabetes but the hypothalamo-pituitary testicular axis alteration might not likely have a major impact as the local defect on steroidogenesis in the testis. This local defect could also predispose to male hypogonadism, i.e. failure of gonadal function.

  16. Methoxychlor induces apoptosis via mitochondria- and FasL-mediated pathways in adult rat testis.

    Science.gov (United States)

    Vaithinathan, S; Saradha, B; Mathur, P P

    2010-04-29

    In the past few years, there has been much concern about the adverse health effects of environmental contaminants in general and organochlorine in particular. Studies have shown the repro-toxic effects of long-term exposure to methoxychlor, a member of the organochlorine family. However, the insight into the mechanisms of gonadal toxicity induced by methoxychlor is not well known. In the present study we sought to elucidate the mechanism(s) underpinning the gonadal effects within hours of exposure to methoxychlor. Experimental rats were divided into six groups of four each. Animals were orally administered with a single dose of methoxychlor (50mg/kg body weight) and killed at 0, 3, 6, 12, 24, and 72h post-treatment. The levels and time-course of induction of apoptosis-related proteins like cytochorome C, caspase 3 and procaspase 9, Fas-FasL and NF-kappaB were determined to assess sequential induction of apoptosis in the rat testis. DNA damage was assessed by TUNEL assay and flowcytometry. Administration of methoxychlor resulted in a significant increase in the levels of cytosolic cytochrome c and procaspase 9 as early as 6h following exposure. Time-dependent elevations in the levels of Fas, FasL, pro- and cleaved caspase 3 were observed. The DNA damage was measured and showed time-dependent increase in the TUNEL positive cells, and also by flowcytometry of testicular cells. The study demonstrates induction of testicular apoptosis in adult rats following exposure to a single dose of methoxychlor.

  17. High Doses of Caffeine during the Peripubertal Period in the Rat Impair the Growth and Function of the Testis

    Directory of Open Access Journals (Sweden)

    Minji Park

    2015-01-01

    Full Text Available Prenatal caffeine exposure adversely affects the development of the reproductive organs of male rat offspring. Thus, it is conceivable that peripubertal caffeine exposure would also influence physiologic gonadal changes and function during this critical period for sexual maturation. This study investigated the impact of high doses of caffeine on the testes of prepubertal male rats. A total of 45 immature male rats were divided randomly into three groups: a control group and 2 groups fed 120 and 180 mg/kg/day of caffeine, respectively, via the stomach for 4 weeks. Caffeine caused a significant decrease in body weight gain, accompanied by proportional decreases in lean body mass and body fat. The caffeine-fed animals had smaller and lighter testes than those of the control that were accompanied by negative influences on the histologic parameters of the testes. In addition, stimulated-testosterone ex vivo production was reduced in Leydig cells retrieved from the caffeine-fed animals. Our results demonstrate that peripubertal caffeine consumption can interfere with the maturation and function of the testis, possibly by interrupting endogenous testosterone secretion and reducing the sensitivity of Leydig cells to gonadotrophic stimulation. In addition, we confirmed that pubertal administration of caffeine reduced testis growth and altered testis histomorphology.

  18. Novel expression of resistin in rat testis: functional role and regulation by nutritional status and hormonal factors.

    Science.gov (United States)

    Nogueiras, Ruben; Barreiro, M Luz; Caminos, Jorge E; Gaytán, Francisco; Suominen, Janne S; Navarro, Victor M; Casanueva, Felipe F; Aguilar, Enrique; Toppari, Jorma; Diéguez, Carlos; Tena-Sempere, Manuel

    2004-07-01

    Resistin, a recently cloned adipose-secreted factor, is primarily involved in the modulation of insulin sensitivity and adipocyte differentiation. However, additional metabolic or endocrine functions of this molecule remain largely unexplored. In this study, a series of experiments were undertaken to explore the potential expression, regulation and functional role of this novel adipocytokine in rat testis. Resistin gene expression was demonstrated in rat testis throughout postnatal development, with maximum mRNA levels in adult specimens. At this age, resistin peptide was immunodetected in interstitial Leydig cells and Sertoli cells within seminiferous tubules. Testicular expression of resistin was under hormonal regulation of pituitary gonadotropins and showed stage-specificity, with peak expression values at stages II-VI of the seminiferous epithelial cycle. In addition, testicular resistin mRNA was down-regulated by the selective agonist of PPARgamma, rosiglitazone, in vivo and in vitro. Similarly, fasting and central administration of the adipocyte-derived factor, leptin, evoked a significant reduction in testicular resistin mRNA levels, whereas they remained unaltered in a model of diet-induced obesity. From a functional standpoint, resistin, in a dose-dependent manner, significantly increased both basal and choriogonadotropin-stimulated testosterone secretion in vitro. Overall, our present results provide the first evidence for the expression, regulation and functional role of resistin in rat testis. These data underscore a reproductive facet of this recently cloned molecule, which may operate as a novel endocrine integrator linking energy homeostasis and reproduction.

  19. Maternal endotoxin-induced fetal growth restriction in rats: Fetal responses in toll-like receptor

    Directory of Open Access Journals (Sweden)

    Banun Kusumawardani

    2012-09-01

    Full Text Available Background: Porphyromonas gingivalis as a major etiology of periodontal disease can produce virulence factor, lipopolysaccharide/LPS, which is expected to play a role in the intrauterine fetal growth. Trophoblast at the maternal-fetal interface actively participates in response to infection through the expression of a family of natural immune receptors, toll-like receptor (TLR. Purpose: the aims of study were to identify endotoxin concentration in maternal blood serum of Porphyromonas gingivalis-infected pregnant rats, to characterize the TLR-4 expression in trophoblast cells, and to determine its effect on fetal growth. Methods: Female rats were infected with live-Porphyromonas gingivalis at concentration of 2 x 109 cells/ml into subgingival sulcus area of the maxillary first molar before and/or during pregnancy. They were sacrified on 14th and 20th gestational day. Fetuses were evaluated for weight and length. Endotoxin was detected by limulus amebocyte lysate assay in the maternal blood serum. The TLR-4 expression in trophoblast cells was detected by immunohistochemistry. 5-azacytidine enhances proliferation in transplanted rat fetal epiglottis.

    Science.gov (United States)

    Marinovic-Kulisic, Sandra; Juric-Lekic, Gordana; Vikic-Topic, Masa; Lokosek, Vedran; Radujkovic, Vedran; Bulic-Jakus, Floriana; Katusic, Ana; Vlahovic, Maja; Serman, Ljiljana; Sincic, Nino

    2011-01-01

    Fetal rat epiglottis and its developmental potential in ectopic transplants under the influence of the epigenetic drug was investigated. Epiglottises from 17-days-old rat embryos were transplanted under kidney capsules of adult rats for 14 days. 5-azacytidine (5 mg/kg) was injected intraperitoneally during first three days and controls were sham treated. TEM, immunohistochemical detection and quantitative stereological analysis of the Proliferating Cell Nuclear Antigen (PCNA) expression (numerical density N(v)) were performed. Typical chondroblasts with long surface processes and sparse lipid droplets were found in fetal epiglottis and chondrocytes with shorter processes, numerous lipid droplets and elastic fibers in adult. PCNA was expressed in almost all cells of the fetal epiglottis while in the adult it was expressed in minority of cells. In transplants, differentiation progressed towards the differentiation found in the adult. Application of 5-azacytidine increased the capacity for proliferation (N(v PCNA)) in comparison to controls but no difference in differentiation was observed. Data about the developmental potential and induction of proliferation in mammalian epiglottis by epigenetic modulation is of importance for regenerative medicine.

  1. Herbal extracts counteract cisplatin-mediated cell death in rat testis

    Institute of Scientific and Technical Information of China (English)

    Amr Amin; Alaaeldin A.Hamza; Amr Kambal; Sayel Daoud

    2008-01-01

    Aim: To evaluate the protective effects of ginger (Gin) and roselle (Ros) against testicular damage and oxidative stress in a cisplatin (CIS)-induced rodent model. Their protective effects against CIS-induced apoptosis in testicular and epididymal sperms is also investigated. Methods: Ethanol extracts of Gin or Ros (1 g/kg-day) were given orally to male albino rats for 26 days. This period began 21 days before a single CIS intraperitoneal injection (10 mg/kg body weight). Results: Gin or Ros given orally significantly restored reproductive function. Both tested extracts notably reduced the CIS-induced reproductive toxicity, as evidenced by restoring the testis normal morphology. In Gin and Ros, the attenuation of CIS-induced damage was associated with less apoptotic cell death both in the testicu-lar tissue and in the sperms. CIS-induced alterations of testicular lipid peroxidation were markedly improved by these plant extracts. Conclusion: The present results provide further insights into the mechanisms of protection against CIS-induced reproductive toxicity and confirm the essential anti-oxidant potential of both examined extracts.

  2. Methoxyethanol biotransformation by liver and testis of rats is modulated by phenobarbital pretreatment

    Energy Technology Data Exchange (ETDEWEB)

    Kaphalia, L.; Au, W.; Moslen, M.T. (Univ. of Texas, Galveston (United States))

    1992-02-26

    Toxicity of 2-methoxyethanol (ME), a widely used solvent, is known to be dependent on its biotransformation by alcohol dehydrogenase to methoxyacetaldehyde (MA) and then by aldehyde dehydrogenase to methoxyacetic acid (MAA). However, little is known about the effects of enzyme inducers on the biotransformation of ME by liver or target organs such as the testis. The authors objective was to examine effects of phenobarbital pretreatment of Sprague Dawley rats on hepatic and testicular biotransformation of ME {r arrow} MA and MA {r arrow} MAA. Phenobarbital diminished hepatic ME {r arrow} MA activity by 80% when activity was calculated per mg prot and by 50% per liver/kg body weight. Hepatic MA {r arrow} MA activity was increased 25% by phenobarbital without an appreciable change in testicular MA {r arrow} MAA activity. Further studies are needed to determine if these effects of phenobarbital pretreatment on tissue biotransformation of ME and MA are associated with changes in the kinetics or toxicity of this solvent.

  3. Cholesterol induces fetal rat enterocyte death in culture

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    Gazzola J.

    2004-01-01

    Full Text Available The effect of cholesterol on fetal rat enterocytes and IEC-6 cells (line originated from normal rat small intestine was examined. Both cells were cultured in the presence of 20 to 80 µM cholesterol for up to 72 h. Apoptosis was determined by flow cytometric analysis and fluorescence microscopy. The expression of HMG-CoA reductase and peroxisome proliferator-activated receptor gamma (PPARgamma was measured by RT-PCR. The addition of 20 µM cholesterol reduced enterocyte proliferation as early as 6 h of culture. Reduction of enterocyte proliferation by 28 and 41% was observed after 24 h of culture in the presence and absence of 10% fetal calf serum, respectively, with the effect lasting up to 72 h. Treatment of IEC-6 cells with cholesterol for 24 h raised the proportion of cells with fragmented DNA by 9.7% at 40 µM and by 20.8% at 80 µM. When the culture period was extended to 48 h, the effect of cholesterol was still more pronounced, with the percent of cells with fragmented DNA reaching 53.5% for 40 µM and 84.3% for 80 µM. Chromatin condensation of IEC-6 cells was observed after treatment with cholesterol even at 20 µM. Cholesterol did not affect HMG-CoA reductase expression. A dose-dependent increase in PPARgamma expression in fetal rat enterocytes was observed. The expression of PPAR-gamma was raised by 7- and 40-fold, in the presence and absence of fetal calf serum, respectively, with cholesterol at 80 mM. The apoptotic effect of cholesterol on enterocytes was possibly due to an increase in PPARgamma expression.

  4. Effect of Bile Acid on Fetal Lung in Rat Model of Intrahepatic Cholestasis of Pregnancy

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    Ling Yu

    2014-01-01

    Full Text Available Objective. To determine the correlation between maternal bile acid (BA level and fetal pulmonary surfactant in rats and study the effects of BA on fetal lung in rat model of intrahepatic cholestasis of pregnancy. Methods. Forty pregnant rats were treated with (A 5.5 mg/kg BA, (B 1.4 mg/kg BA, and (C 1 ml physiological saline. Levels of total bile acid (TBA, ALT, AST, TBIL, DBIL, and SP-A were determined and the lungs of fetal rats were analyzed for pathological changes. Results. Groups A and B intervened with BA showed significant higher level of TBA in both maternal and fetal serum, more mortality rate of fetal rats, more concentration of SP-A in fetal serum, and wider alveolus mesenchyme of fetal rats than the control Group C. Higher level of BA associated with increased fetal risk and lower numerical density of mitochondria in type II alveolar epithelial cells. The levels of TBA in maternal serum were found to have significant positive correlation with those in fetal serum and SP-A level but negatively with the area of alveolus and the numerical density of lamellar body. Conclusions. The TBA level in maternal serum showed significant association with lung pathological changes in fetal rats.

  5. Stimulation of fetal hypothalamus induces uterine contractions in pregnant rats at term.

    Science.gov (United States)

    Endoh, Hisashi; Fujioka, Takashi; Endo, Hideki; Inazuka, Yukiko; Furukawa, Susumu; Nakamura, Shoji

    2008-10-01

    The fetal brain is thought to have a role in the onset and progression of labor. Evidence also exists for fetal oxytocin release just before and during parturition. The present study examined whether activation of the fetal brain could induce uterine myometrial contractions through oxytocin receptors in the dam. Under urethane anesthesia, electrical stimulation of the hypothalamus of fetal rats that were still connected with the dams by an intact umbilical cord induced uterine contractions in term pregnant rats. Intraperitoneal injections of synthetic oxytocin in fetuses induced uterine contractions in the dams similar to those induced by electrical stimulation of the fetal hypothalamus. Maternal intravenous injections of an oxytocin antagonist immediately attenuated uterine contractions induced by fetal oxytocin injections and electrical stimulation of the fetal hypothalamus. These findings suggest the possibility that oxytocin released from the fetal hypothalamus is involved in parturition.

  6. Testis-derived Sertoli cells have a trophic effect on dopamine neurons and alleviate hemiparkinsonism in rats.

    Science.gov (United States)

    Sanberg, P R; Borlongan, C V; Othberg, A I; Saporta, S; Freeman, T B; Cameron, D F

    1997-10-01

    Neural tissue transplantation has become an alternative treatment for Parkinson's disease (PD) and other neurodegenerative disorders. The clinical use of neural grafts as a source of dopamine for Parkinson's disease patients, although beneficial, is associated with logistical and ethical issues. Thus, alternative graft sources have been explored including polymer-encapsulated cells and nonneural cells (that is, adrenal chromaffin cells) or genetically modified cells that secrete dopamine and/or trophic factors. Although progress has been made, no current alternative graft source has ideal characteristics for transplantation. Emerging evidence suggests the importance of trophic factors in enhancing survival and regeneration of intrinsic dopaminergic neurons. It would be desirable to transplant cells that are readily available, immunologically accepted by the central nervous system and capable of producing dopamine and/or trophic factors. Sertoli cells have been shown to secrete CD-95 ligand and regulatory proteins, as well as trophic, tropic, and immunosuppressive factors that provide the testis, in part, with its "immunoprivileged" status. The present study demonstrated that transplantation of rat testis-derived Sertoli cells into adult rat brains ameliorated behavioral deficits in rats with 6-hydroxydopamine-induced hemiparkinsonism. This was associated with enhanced tyrosine hydroxylase (TH) immunoreactivity in the striatum in the area around the transplanted Sertoli cells. Furthermore, in vitro experiments demonstrated enhanced dopaminergic neuronal survival and outgrowth when embryonic neurons were cultured with medium in which rat Sertoli cells had been grown. Transplantation of Sertoli cells may provide a useful alternative treatment for PD and other neurodegenerative disorders.

  7. Long term Exposure to Extremely Low Frequency Electromagnetic Field Affects Sex Hormones Level and Structure of Testis in Rats

    Directory of Open Access Journals (Sweden)

    T.S. Javadifar

    2012-01-01

    Full Text Available Extremely Low Frequency Electromagnetic Fields (ELFEMFs are produced by a variety of different sources. The aim of this study was to evaluate the influence of ELFEMF on function and structure of testis in rats. Experimental adult male Wistar rats were exposed to a 50 Hz ELFEMF, 1 MT (emitted from solenoid for 24 h daily during 135 days. The sham rats were subjected to sham exposure and the control rats were kept in animal room. In final, blood samples collected for the determination of the testosterone, LH and FSH concentration in the plasma. The testis was examined using light microscopy. Results showed that in EMF exposed group plasma concentration of testosterone was decreased (p<0.001, plasma LH concentration was increased (p<0.01 and FSH showed no significant changes which were accompanied by marked atrophy of seminiferous tubules and marked increase in interstitial connective tissue as well as Leydig cell hyperplasia. In conclusion, long term exposure to ELFEMF could have adverse effects on mammalian reproduction.

  8. Steroidogenic enzyme histochemistry in the testis of Sprague Dawley rats following the administration the water extracts from Carica papaya seed.

    Science.gov (United States)

    Uche-Nwachi, E O; Mitchell, C V; McEwen, C

    2011-01-01

    Water extracts from pawpaw seed have been reported to reversibly decrease the testicular weight and to suppress spermatogenesis, and fertility of Wistar rats. The reversible changes become evident, 30 - 45 days after the withdrawal of the extract. The possible effect of this extract on the activities of steroidogenic enzymes of the testis has not been investigated. Water extract of papaya seeds was administered to male Sprague Dawley rats ad libitum for 84 days. Following the discontinuation of the extracts, ten rats each were sacrificed on days 0, 10, 20 and 30 after the withdrawal. Their testes were quickly dissected out and frozen. Cryostat sections, 10µm thick were cut. These sections were used for immunohistochemical stains for side chain cleavage enzyme and aromatase, and for histochemical stains for 17-β Hydroxysteroid dehydrogenase, 3-β Hydroxysteroid dehydrogenase. We conclude that the water extract of papaya seed suppresses the activities of steroidogenic enzymes in the testis of Sprague Dawley rats, and that this may contribute to reversible suppression of spermatogenesis, a property that gives a possible male contraceptive potential.

  9. Passive stiffness of rat skeletal muscle undernourished during fetal development

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    Ana Elisa Toscano

    2010-01-01

    Full Text Available OBJECTIVES: The aim of the study was to investigate the effect of fetal undernutrition on the passive mechanical properties of skeletal muscle of weaned and young adult rats. INTRODUCTION: A poor nutrition supply during fetal development affects physiological functions of the fetus. From a mechanical point of view, skeletal muscle can be also characterized by its resistance to passive stretch. METHODS: Male Wistar rats were divided into two groups according to their mother's diet during pregnancy: a control group (mothers fed a 17% protein diet and an isocaloric low-protein group (mothers fed a 7.8% protein diet. At birth, all mothers received a standardized meal ad libitum. At the age of 25 and 90 days, the soleus muscle and extensor digitorum longus (EDL muscles were removed in order to test the passive mechanical properties. A first mechanical test consisted of an incremental stepwise extension test using fast velocity stretching (500 mm/s enabling us to measure, for each extension stepwise, the dynamic stress (σd and the steady stress (σs. A second test consisted of a slow velocity stretch in order to calculate normalized stiffness and tangent modulus from the stress-strain relationship. RESULTS: The results for the mechanical properties showed an important increase in passive stiffness in both the soleus and EDL muscles in weaned rat. In contrast, no modification was observed in young adult rats. CONCLUSIONS: The increase in passive stiffness in skeletal muscle of weaned rat submitted to intrauterine undernutrition it is most likely due to changes in muscle passive stiffness.

  10. Ultrastructural localization of silver in rat testis and organ distribution of radioactive silver in the rat

    DEFF Research Database (Denmark)

    Ernst, E; Rungby, J; Baatrup, E

    1992-01-01

    The deposition of silver after a single intravenous injection (2 micrograms Ag g-1 body weight) was studied in the testes of Wistar rats 24 h and 1 and 2 weeks after dosing with radiolabelled 110AgNo3 (2 micrograms Ag and 1.2 kBq g-1 body weight). Also, the temporal accumulation of silver during ...

  11. Zinc antagonizes homocysteine-induced fetal heart defects in rats.

    Science.gov (United States)

    He, Xiaoyu; Hong, Xinru; Zeng, Fang; Kang, Fenhong; Li, Li; Sun, Qinghua

    2009-09-01

    It has been suggested that zinc may have a protective role against heart defects during fetal development. We investigated the effects of zinc on the development of fetal cardiac malformations induced by homocysteine. Pregnant Sprague-Dawley rats were randomized into one of five groups: control (C), homocysteine (H), homocysteine + zinc (Z), homocysteine + folic acid (F), or homocysteine + zinc + folic acid (ZF) (each n = 8). Homocysteine (8 nmol/day) was administered intraperitoneally in the H, Z, F, and ZF groups on gestation days (GD) 8, 9, and 10. Zinc (30 mg/kg day), folic acid (30 mg/kg day), or both (30 mg/kg day each) were administered intragastrically daily in the Z, F, and ZF groups, respectively, throughout the pregnancy. In each group, two fetuses were removed on GD 13, 15, 17, and 19 and examined for cardiac malformations; maternal copper/zinc-containing-superoxide dismutase (Cu/Zn-SOD) activity and metallothionein type I (MT-1) mRNA expression were measured simultaneously. The prevalence of cardiac malformations was significantly higher in group H than in group C, and significantly lower in group Z than in group H at the studied time points. Cu/Zn-SOD activity and MT-1 mRNA levels were significantly lower in group H than in group C, and significantly higher in group Z than in group H. Our data suggest that zinc antagonizes homocysteine-induced teratogenic effects on the fetal heart, possibly via the inhibition of excessive peroxidation.

  12. Effects of Maternal Lead Acetate Exposure during Lactation on Postnatal Development of Testis in Offspring Wistar Rats

    Directory of Open Access Journals (Sweden)

    Mehran Dorostghoal

    2011-03-01

    Full Text Available Objective(sDuring recent years, there has been an increasing interest in contribution of environmental pollutants as heavy metals to human male infertility. Present study was aimed to investigate the effects of maternal lead acetate exposure during lactation on postnatal development of testis in offspring rats.Materials and MethodsA total of 60 female rats randomly divided into four equal groups; control and three treatment groups received 20, 100 and 300 mg/kg/day lead acetate via drinking water from day 2 to day 21 of lactation. At 7, 14, 21, 28, 60, 90 and 120 days after birth, the testis weight and volume of offspring were measured and their epididymal semen analyzed. Following tissue processing, 5 μm sections were stained with haematoxylin-eosin and evaluated with quantitative techniques. Testicular parameters in different groups were compared by one-way ANOVA.ResultsTestis weight and volume of offspring decreased significantly in a dose-related manner in moderate (P< 0.05 and high (P< 0.01 doses groups. Dose-dependent significant reductions were seen in seminiferous tubules diameter and germinal epithelium height during neonatal, prepubertal and postpubertal periods in moderate (P< 0.05 and high (P< 0.01 doses groups until 90 and 120 days after birth, respectively. Significant decreases were observed in mean sperm density of offspring at puberty in moderate and high doses groups until 90 and 120 days after birth, respectively. Testosterone levels decreased significantly in a dose-related manner at puberty in moderate and high doses groups. ConclusionPresent study showed maternal lead acetate exposure during lactation caused dose-related and long-term alterations of testicular parameters in offspring rats.

  13. Effect of in utero exposure to endocrine disruptors on fetal steroidogenesis governed by the pituitary-gonad axis: a study in rats using different ways of administration.

    Science.gov (United States)

    Kariyazono, Yudai; Taura, Junki; Hattori, Yukiko; Ishii, Yuji; Narimatsu, Shizuo; Fujimura, Masatake; Takeda, Tomoki; Yamada, Hideyuki

    2015-12-01

    The effects of endocrine disruptors on testicular steroidogenesis in fetal rats were investigated in a study involving in utero exposure. In the major part of this study, pregnant rats at gestational day (GD)15 were given a single oral administration of the test substance, and then the expression of the following mRNAs in GD20 fetuses was determined: testicular steroidogenic acute-regulatory protein (StAR), a cholesterol transporter mediating the rate-limiting step of steroidogenesis, a ß-subunit of pituitary luteinizing hormone (LH), and a regulator of gonadal steroidogenesis. Among the substances tested, only di(2-ethylhexyl)phthalate (DEHP) reduced the expression of fetal testicular StAR. The others listed below exhibited little effect on fetal StAR: 2,2',4,4'-tetrabromodiphenylether, tributyltin chloride, atrazine, permethrin, cadmium chloride (Cd), lead acetate (Pb) and methylmercury (CH3HgOH). None of them, including DEHP, lacked the ability to reduce the expression of pituitary LHß mRNA. The present study also examined the potential of metals as modifiers of fetal steroidogenesis by giving them to pregnant dams in drinking water during GD1 and GD20. Under these conditions, Cd and Pb at a low concentration (0.01 ppm) significantly attenuated the fetal testicular expression of StAR mRNA without a concomitant reduction in LHß. No such effect was detected with CH3HgOH even at 1 ppm. These results suggest that: 1) DEHP, Cd and Pb attenuate the fetal production of sex steroids by directly acting on the testis, and 2) chronic treatment during the entire gestational period is more useful than a single administration for determining the hazardous effect of a suspected endocrine disruptor on fetal steroidogenesis.

  14. Ontogeny of innervation of rat and ovine fetal adrenals.

    Science.gov (United States)

    Engeland, W C; Wotus, C; Rose, J C

    1998-01-01

    The formation of adrenocortical zonation occurs in rats during late gestation. Since adult cortical function is modulated by neural mediators, it is possible that the development of differentiated function is dependent on cortical innervation. The goal of this study was to compare the pattern and timing of rodent and ovine adrenal innervation during late organogenesis by staining with antibodies directed against the neuropeptides vasoactive intestinal peptide (VIP), calcitonin gene-related peptide (CGRP) and neuropeptide tyrosine (NPY) and the catecholamine biosynthetic enzyme, tyrosine hydroxylase (TOH). Rat adrenals were collected from fetal days 17-21 (term=21 days) and ovine adrenals from fetal days 101-136 (term=145 days). Adrenals were fixed, cryosectioned at 100 microns and immunostained using Cy3-conjugated secondary antibodies. In both species, staining of VIP, CGRP, NPY and TOH fibers was observed in the capsule and subcapsular layers of the cortex during gestation. In late gestation, VIP- and NPY-positive ganglions cells were observed near the medulla extending processes toward the outer cortex; in ovine adrenals, fibers from ganglion cells appeared to surround nests of outer cortical (presumably, zona glomerulosa) cells. These data show that phenotypically distinct neural elements appear at different stages of adrenocortical development. The presence of neural elements in contact with adrenal cortical cells supports the possibility for neural control of adrenocortical development.

  15. Reduced body mass, food intake, and testis size in response to short photoperiod in adult F344 rats

    Directory of Open Access Journals (Sweden)

    Heideman Paul D

    2002-07-01

    Full Text Available Abstract Background Although laboratory rats are often considered classic nonseasonal breeders, peripubertal rats of two inbred strains, F344 and BN, have both reproductive and nonreproductive responses to short photoperiods. Unmanipulated adult rats have not been reported to have robust responses to short photoperiod alone, although several treatments can induce photoperiodic responses in adults. In this study, we tested the hypotheses that unmanipulated F344 rats retain responses to short photoperiod as adults and that they have the necessary elements for an endogenous circannual rhythm of sensitivity to short photoperiod. Results Relative to rats kept in long photoperiods (L16:D8, adult F344 rats transferred at 4.5 months of age to short photoperiods (L8:D16 had significantly lower testis size, food intake, and body weight. In a second experiment, newly weaned F344 rats underwent an initial period of inhibition of reproductive maturation, lower food intake, and lower body weight in short photoperiod or intermediate photoperiod (L12:D12 relative to rats in long photoperiod. By 18 weeks of treatment, rats in the two inhibitory photoperiods no longer differed from long photoperiod controls. In short photoperiod, rats underwent a second period of slight reproductive inhibition between weeks 35 and 48, but there was an effect on body weight and slight inhibition of food intake only in an intermediate photoperiod. Conclusion Male F344 rats retain photoresponsiveness as adults, with less reproductive inhibition but equivalent nonreproductive responses. There was only weak evidence for an endogenous timer controlling a circannual cycle of sensitivity to short photoperiod.

  16. Ultrastructural localization of silver in rat testis and organ distribution of radioactive silver in the rat

    DEFF Research Database (Denmark)

    Ernst, E; Rungby, J; Baatrup, E

    1992-01-01

    The deposition of silver after a single intravenous injection (2 micrograms Ag g-1 body weight) was studied in the testes of Wistar rats 24 h and 1 and 2 weeks after dosing with radiolabelled 110AgNo3 (2 micrograms Ag and 1.2 kBq g-1 body weight). Also, the temporal accumulation of silver during...... the experimental period was monitored in the blood, testes, epididymides, kidney, liver and brain. The subcellular distribution of silver within the testes was demonstrated by using the histochemical technique of autometallography. Silver was cleared rapidly from the blood. After an initial rise, concentrations...... in organs remained almost stable throughout the experimental period. Silver was especially abundant in interstitial macrophages and in the basement membrane. Deposits of silver were found in all cell types of spermatogenesis and in the lysosomes of the Sertoli cells. Udgivelsesdato: 1991-Oct...

  17. Comparative Study on Histopatological and Histomorphometric Effect of Raw and Cooked Garlic on Spermatogenesis in Testis and Epidydims of Rats

    Directory of Open Access Journals (Sweden)

    khadijeh bahrami

    2014-03-01

    Full Text Available Background &Objective: The present study aims at studying two forms of raw and cooked garlic to identify the effect of this plant on the amount of change in histopatological of spermatogenesis of wistar rat.Materials & Methods: 40 male rats were divided into five equal groups (4 treatment 1 control group the first and second treatment were received palete food consisted of 5% and 15% of raw garlic every day. The third and fourth reatment were received palete food consisted of 5%and 15% of cooked garlic as a food . The control group received standard palete food every day in a month. Finally,the testis were taken out of stomach and after preparing tissue and coloring, they were gone under microscopic studies. Thence, the data were analyzed using SPSS and Duncan test.Results: The study indicated that the amount of sexual cells in the group having cook garlic for 15% compared with that of controlled group had a significant increase and the amount of sexual cells in the group using raw garlic as a food had a significant decrease compared with that of the controlled group.Conclusion: Prescription of cooked garlic has an influence on Proliferation of sexual cells in testicular tubules and epidydymes and so increased spermatogenesis in this group in caparison with the control group. However, prescribing raw garlic has harmful effects on tissue of testis and process of spermatogenes in empric compared with the control group.

  18. The Effects of Trifluralin on LH, FSH and Testosterone Hormone Levels and Testis Histological Changes in Adult Rats

    Directory of Open Access Journals (Sweden)

    Mehrdad Shariati

    2008-01-01

    Full Text Available Background: Trifluralin is a herbicide and used in agriculture widely. It enters plants throughdeveloping roots and stops plant cells from division and elongation (meristemic inhibitor.Extensive application of trifluralin to control annual grasses and broadleaf weeds in agriculture,horticulture and horn garden, leads to environmental pollution and its entrance into the food chaincould have determined effects on human and other species. In this research the effects of trifluralinon reproductive parameters of the male rats including serum luteinizing hormone (LH, folliclestimulatinghormone (FSH, testosterone levels, and changes in testicular tissue and body weightwere investigated.Materials and Methods: For this purpose male rats were randomly divided in 5 groups, to includecontrol, sham (received normal saline as a solvent, and three experimental groups which received500, 1000 and 2000 mg/kg oral trifluralin respectively. After 16 days, body and testis weight weremeasured and blood samples were taken from heart and used for measurement of LH, FSH andtestosterone levels. To evaluate histological changes, testes were removed and weighed and, afterobtaining tissue section, stained by HE.Results: Serum testosterone, FSH, and LH levels showed significant decrease in experimentalgroups (p<0.05. There was significant decrease in the number of germinal and somatic cells intestis in experimental groups. There was also a significant decrease in body and testis weight inexperimental groups.Conclusion: It can be concluded that oral administration of trifluralin could decrease gonadotropinsand testosterone hormone levels and also this herbicide could have hazardous effects on testistissue.

  19. Fetal hydantoin syndrome: inhibition of placental folic acid transport as a potential mechanism for fetal growth retardation in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Will, M.; Barnard, J.A.; Said, H.M.; Ghishan, F.K.

    1985-04-01

    Maternal hydantoin ingestion during pregnancy results in a well defined clinical entity termed ''fetal hydantoin syndrome''. The clinical characteristics of this syndrome includes growth retardation, and congenital anomalies. Because folic acid is essential for protein synthesis and growth, and since hydantoin interferes with intestinal transport of folic acid, the authors postulated that part of the fetal hydantoin syndrome may be due to inhibition of placental folic acid by maternal hydantoin. Therefore, they studied in vivo placental folate transport in a well-established model for fetal hydantoin syndrome in the rat. Our results indicate that maternal hydantoin ingestion, significantly decreased fetal weight and placental and fetal uptake of folate compared to controls. To determine whether maternal hydantoin ingestion has a generalized or specific effect on placental function, they examined placental and fetal zinc transport in the same model. Our results indicate that zinc transport is not altered by hydantoin ingestion. They conclude that maternal hydantoin ingestion results in fetal growth retardation which may be due in part to inhibition of placental folate transport.

  20. The function of oestradiol and its receptor in the rat testis

    NARCIS (Netherlands)

    W.M.O. van Beurden-Lamers (Wilma)

    1977-01-01

    textabstractThe testis consists of 2 different tissues i.e. the interstitial tissue, which is the site of steroidogenesis, and seminiferous tubules where spermatogenesis occurs. Testosterone production takes place in the Leydig cells of the interstitial tissue and is under the influence of the tropi

  1. Latent inhibition of a conditioned taste aversion in fetal rats.

    Science.gov (United States)

    Mickley, G Andrew; Hoxha, Zana; DiSorbo, Anthony; Wilson, Gina N; Remus, Jennifer L; Biesan, Orion; Ketchesin, Kyle D; Ramos, Linnet; Luchsinger, Joseph R; Prodan, Suzanna; Rogers, Morgan; Wiles, Nathanael R; Hoxha, Nita

    2014-04-01

    The etiology of schizophrenia's cognitive symptoms may have its basis in prenatal alterations of glutamate N-methyl-D-aspartate (NMDA) receptor functioning. Therefore, the current study investigated the effects of ketamine (an NMDA receptor blocking drug) on both a conditioned taste aversion (CTA) and latent inhibition (LI; a model of attentional capacity) in rat fetuses. We first sought to determine if a CTA could be diminished by nonreinforced preexposure to a CS in fetal rats (i.e., LI). We injected E18 pregnant Sprague-Dawley rats with 100% allicin (garlic taste) or an equal volume of saline. Some of the pregnant dams also received ketamine (100 mg/kg, i.p.). One day later (E19), the dams received a second injection of the CS, followed by either lithium chloride (the US) or saline. Finally, on E21 pups received oral lavage with allicin and observations of ingestive orofacial motor responses were recorded. When allicin had been paired with LiCl in utero, E21 fetuses exhibited a conditioned suppression of orofacial movements, indicative of an aversion to this taste. Preexposure to the garlic taste on E18 produced a LI of this CTA. Ketamine significantly disrupted the formation of the CTA and had some impact on LI. However, the direct effect of ketamine on LI is less certain since the drug also blocked the original CTA.

  2. Role of light in the mediation of acute effects of a single afternoon melatonin injection on steroidogenic activity of testis in the rat

    Indian Academy of Sciences (India)

    Saumen K Maitra; Arun K Ray

    2000-09-01

    Young adult male rats, maintained either in an LD 12 : 12 or in continuous illumination (LL) for one week, were given a single injection of 25 g melatonin/100 g body wt or ethanolic-saline (control) at 17.00 h. Animals from each group were sacrificed at 11.00 h on the following day. The activity of two important steroidogenic enzymes, 17-hydroxysteroid dehydrogenase (17-HSD) and Δ5-3-hydroxysteroid dehydrogenase (Δ5-3-HSD), and serum concentrations of testosterone, were measured following highly specific and sensitive spectrophotometric techniques and RIA, respectively. A significant decrease in the activity of both the steroidogenic enzymes was noted in the testes of melatonin-treated rats maintained under normal light-dark schedules, but this response was found to be lacking in the LL rats. However, no significant changes in the level of serum testosterone were noted in either group of melatonin-treated rats from the values in respective groups of ethanolic saline-administered LD and LL rats. Exposure of ethanolic saline-injected rats to continuous light also did not cause any change in the steroidogenic activity of the testis from those in LD rats. The study indicates that continuous light as such does not affect the endocrine function of testis but abolishes suppressive effects of melatonin on the steroidogenic activity of the testis in rat.

  3. Acute and sub-acute effects of 2-butenoic acid-3-(diethoxy phosphinothioyl) methyl ester (RPR-II) on testis of albino rat.

    Science.gov (United States)

    Khan, I A; Reddy, B V; Mahboob, M; Rahman, M F; Jamil, Kaiser

    2002-02-01

    Acute and sub-acute toxic effects of a novel phosphorothionate coded as RPR-II on testis of albino rats were studied. In acute study rats received a single dose of 12.3 mg/kg of RPR-II and sacrificed after 24 hr. For sub-acute study 0.58 mg/kg/day was administered orally to rats for 10 and 21 days. Acute exposure of rats to RPR-II brought no change either in the gonadosomatic index (GSI) or in the structure of testis or in the serum levels of testosterone. Testis glutathione (GSH) level and glutathione S-transferase (GST) activity was significantly decreased whereas, acid phosphatase (AcP) levels increased significantly at 24 hr post-treatment. On 7th day (withdrawal period) after the cessation of the treatment the GSH, GST, AcP, and AkP levels reached to near control. The sub-acute study revealed a significant decrease in GSI on 10th and 21st day of the treatment. In contrast, a time-dependent and significant increased in GSH level and GST activity was observed on 100th and 21st day of post-treatment, except GSH level on 10th day, which was declined. Due to RPR-II treatment the testis AcP and alkaline phosphatase (AkP) levels were significant at both 10th and 21st day of medication but AcP levels were increased whereas AkP levels decreased. The histopathological studies on day 10th showed considerable loss of spermatozoids in testis and at 21st day complete derangement of cellular organization was observed. Testosterone levels decreased significantly on 10th day and remained significantly low at 21st day. However, withdrawal studies showed a recovery in testis of rat treated with RPR-II. GST, GSH, GSI, AcP and AkP values recovered, testosterone levels were also well recovered but recovery in testis structure remained at a low profile. The present study suggests that RPR-II may cause testicular toxicity in rats affecting the normal functioning of testis and it also gave some new information in withdrawal studies.

  4. Localization of cytochrome P450 and related enzymes in adult rat testis and downregulation by estradiol and bisphenol A.

    Science.gov (United States)

    Gilibili, Ravindranath Reddy; Vogl, A Wayne; Chang, Thomas K H; Bandiera, Stelvio M

    2014-07-01

    There is a growing body of evidence that exposure to endocrine disrupting chemicals and to estrogenic compounds in particular can affect the testis and male fertility. In the present study, the constitutive expression of steroidogenic and non-steroidogenic cytochrome P450 (CYP) and related enzymes in adult rat testis, and their regulation by estradiol and bisphenol A, were investigated. CYP1B1, CYP2A1, NADPH-cytochrome P450 oxidoreductase (POR) and microsomal epoxide hydrolase (mEH) proteins, together with CYP17A1 and 3β-hydroxysteroid dehydrogenase (HSD3B), were detected by immunoblot analysis in testicular microsomes prepared from untreated adult Sprague Dawley rats. In contrast, CYP1A, CYP2B, CYP2E, CYP2D, CYP2C, CYP3A, and CYP4A enzymes were not detected. Immunofluorescence staining of cryosections of perfusion-fixed testes showed that CYP1B1, CYP2A1, CYP17A1, and HSD3B were expressed exclusively or mainly in interstitial cells, whereas mEH and POR protein staining was detected both in interstitial cells and in seminiferous tubules. Testicular CYP1B1 and CYP2A1 protein levels were decreased following treatment of adult rats with estradiol benzoate at 0.004, 0.04, 0.4, or 4 μmol/kg/day or bisphenol A at 400 or 800 μmol/kg/day, for 14 days, whereas expression of HSD3B was unaffected. Testicular CYP17A1, POR, and mEH protein expression was also downregulated at the three highest dosages of estradiol benzoate and at both dosages of bisphenol A. The present study is the first to establish the cellular localization of CYP1B1, mEH, and POR in rat testis and to demonstrate the suppressive effect of bisphenol A on testicular CYP1B1, CYP2A1, mEH, and POR protein levels.

  5. Comparative study on influence of fetal bovine serum and serum of adult rat on cultivation of newborn rat neural cells

    Directory of Open Access Journals (Sweden)

    Sukach A. N.

    2014-09-01

    Full Text Available Aim. To study the influence of fetal bovine serum and serum of adult rats on behavior of newborn rat isolated neural cells during their cultivation in vitro. Methods. The isolation of neural cells from neonatal rat brain. The determination of the dynamics of cellular monolayer formation. Immunocytochemical staining of cells for β-tubulin III, nestin and vimentin. Results. It has been determined that the addition of serum of adult rats to the cultivation medium creates more favorable conditions for survival, attachment and spread of differentiated, and proliferation of the stem/progenitor neural cells of newborn rats during cultivation in vitro compared with the fetal bovine serum. Conclusions. Using the serum of adult rats is preferable for the cultivation of isolated neural cells of newborn rats compared with the fetal bovine serum.

  6. Palmitate attenuates osteoblast differentiation of fetal rat calvarial cells

    Energy Technology Data Exchange (ETDEWEB)

    Yeh, Lee-Chuan C.; Ford, Jeffery J. [Department of Biochemistry, The University of Texas Health Science Center at San Antonio, TX (United States); Lee, John C. [Department of Biochemistry, The University of Texas Health Science Center at San Antonio, TX (United States); The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, TX (United States); Adamo, Martin L., E-mail: adamo@biochem.uthscsa.edu [Department of Biochemistry, The University of Texas Health Science Center at San Antonio, TX (United States); The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, TX (United States)

    2014-07-18

    Highlights: • Palmitate inhibits osteoblast differentiation. • Fatty acid synthase. • PPARγ. • Acetyl Co-A carboxylase inhibitor TOFA. • Fetal rat calvarial cell culture. - Abstract: Aging is associated with the accumulation of ectopic lipid resulting in the inhibition of normal organ function, a phenomenon known as lipotoxicity. Within the bone marrow microenvironment, elevation in fatty acid levels may produce an increase in osteoclast activity and a decrease in osteoblast number and function, thus contributing to age-related osteoporosis. However, little is known about lipotoxic mechanisms in intramembraneous bone. Previously we reported that the long chain saturated fatty acid palmitate inhibited the expression of the osteogenic markers RUNX2 and osteocalcin in fetal rat calvarial cell (FRC) cultures. Moreover, the acetyl CoA carboxylase inhibitor TOFA blocked the inhibitory effect of palmitate on expression of these two markers. In the current study we have extended these observations to show that palmitate inhibits spontaneous mineralized bone formation in FRC cultures in association with reduced mRNA expression of RUNX2, alkaline phosphatase, osteocalcin, and bone sialoprotein and reduced alkaline phosphatase activity. The effects of palmitate on osteogenic marker expression were inhibited by TOFA. Palmitate also inhibited the mRNA expression of fatty acid synthase and PPARγ in FRC cultures, and as with osteogenic markers, this effect was inhibited by TOFA. Palmitate had no effect on FRC cell proliferation or apoptosis, but inhibited BMP-7-induced alkaline phosphatase activity. We conclude that palmitate accumulation may lead to lipotoxic effects on osteoblast differentiation and mineralization and that increases in fatty acid oxidation may help to prevent these lipotoxic effects.

  7. Maternal exposure to diphenhydramine during the fetal period in rats: effects on physical and neurobehavioral development and on neurochemical parameters.

    Science.gov (United States)

    Moraes, A P; Schwarz, A; Spinosa, H S; Florio, J C; Bernardi, M M

    2004-01-01

    Previous research from our laboratory suggested that the administration of antihistaminics (H(1) receptor antagonists) to pregnant Wistar rats throughout pregnancy altered brain sexual differentiation and dopaminergic physiology of the offspring. In the present study, we assessed the effects of 20 mg/kg diphenhydramine (DPH) administration to pregnant rats during the fetal period of pregnancy [Gestation Days (GDs) 16-21], a critical period for brain sexual differentiation and central nervous system (CNS) maturation. Maternal body weight and water and food consumption were measured during pregnancy and offspring physical and behavioral development were evaluated during lactation. Offspring open-field behavior was assessed at 21 and 100 days of age. After the final open-field test, male and female sexual behavior, stereotypy following an apomorphine challenge, striatal content of dopamine (DA), the dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA), serotonin (5-HT) and the serotonin metabolite 5-hydroxyindolacetic acid (5-HIAA) were assessed. There were no significant treatment-related changes in maternal reproductive parameters, but DPH treatment decreased maternal body weight gain during the treatment period. Offspring physical parameters were not altered in the treated group, and no significant treatment-related changes were found in female open-field measures, sexual behavior or in striatal neurochemical measurements. However, delayed testis descent and altered patterns of sexual behavior occurred in male offspring accompanied by increased striatal DA, decreased striatal DOPAC as well as reduced DOPAC/DA, HVA/DA and 5-HIAA/5-HT ratios. Taken together, these data suggest that exposure to DPH during the fetal period of rat development altered postnatal CNS maturation and sexual development of male offspring via changes in striatal bioamine systems.

  8. Embryotoxicity and fetal toxicity of nickel in rats

    Energy Technology Data Exchange (ETDEWEB)

    Sunderman, F.W Jr.; Shen, S.K.; Mitchell, J.M.; Allpass, P.R.; Damjanov, I.

    1978-01-01

    Embryotoxicity and fetal toxicity of nickel chloride (NiCl/sub 2/) and nickel subsulfide (Ni/sub 3/S/sub 2/) were studied in Fischer rats. Injection of NiCl/sub 2/ (16 mg of Ni/kg, im) on Day 8 of gestation reduced the man number of live pups per dam and resulted in diminisehd body weights of fetuses on Day 20 of gestation and of weanlings at 4 to 8 weeks after birth. Injection of Ni/sub 2/S/sub 2/ (80 mg of Ni/kg, im) on Day 6 of gestation reduced the mean number of live pups per dam. No congenital anomalies were found in fetuses from any Ni-treated dams, including dams that recieved 10 im injections of NiCl/sub 2/ (2 mg of Ni/kg, twice daily, on Days 6 to 10 of gestation). /sup 63/NiCl/sub 2/ (12 mg of Ni/kg, im) was administered to a group of nonpregnant female rats and to groups of pregnant rats on Day 8 or 18 of gestation. After 24 hr, the relative concentrations of /sup 63/Ni in tissues were: kidney > serum > adrenal approx. = lung approx. = ovary > spleen approx. = heart approx. = liver > skeletal muscle. Pituitary /sup 63/Ni concentrations were much higher in pregnant rats than in non-pregnant females. /sup 63/Ni concentrations in products of conception (embryos and embryonic membranes) on Day 9 and in placentas on Day 19 were equivalent to /sup 63/Ni concentrations in adrenal, lung, and ovary tissues of the dams. Autoradiography of fetuses and placentas on Day 19 of gestation showed /sup 63/Ni localization in fetal urinary bladders and in the basal laminae and yolk sacs of the placentas. These studies show (a) that im injection of NiCl/sub 2/ and Ni/sub 3/S/sub 2/ during early gestation causes embryonic mortality at dosages that do not cause maternal mortality, and (b) that /sup 63/Ni(II) can cross the feto-maternal barriers and enter the fetuses during late gestation.

  9. A Short-term In vivo Screen using Fetal Testosterone Production, a Key Event in the Phthalate Adverse Outcome Pathway, to Predict Disruption of Sexual Differentiation.

    Science.gov (United States)

    This study was designed to develop and validate a short-term in vivo protocol termed the Fetal Phthalate Screen (FPS) to detect phthalate esters (PEs) and other chemicals that disrupt fetal testosterone synthesis and testis gene expression in rats. We propose that the FPS can be ...

  10. Diagnosis of testicular torsion by measuring attenuation of dual wavelengths in transmission geometry across the testis: an experimental study in a rat model.

    Science.gov (United States)

    Canpolat, Murat; Yucel, Selcuk; Sircan-Kucuksayan, Aslinur; Kol, Arif; Kazanci, H Ozgur; Denkceken, Tuba

    2012-04-01

    To develop a noninvasive and real-time dual-wavelengths optic system to detect testicular torsion in an animal model. Diagnosis of testicular torsion is challenging in emergency conditions and frequently ends with surgical exploration. In this study, 9 male 8-month-old Wistar albino rats weighing an average of 400 g were used. A transverse incision on the upper scrotum was done and the right testis was torsed with a 720° medial rotation. The other testis of each rat was used as the control or sham group. In the sham group, the testicle was moved out of the body but no torsion was applied before repositioning into the scrotum. Transmission of continuous-wave light through all testes at wavelengths of 660 nm and 940 nm were measured. The ratio of the average intensities of the transmitted light of both wavelengths--660 nm to 940 nm--was used as a parameter to diagnose testis torsion. The ratios were significantly different (P = .001) between the torsion group and control group. Our noninvasive technique measuring attenuation of dual wavelengths in transmission geometry across the testis has the ability to distinguish between the testis with and without torsion on the basis of a threshold value of the ratio. Copyright © 2012 Elsevier Inc. All rights reserved.

  11. Effects of prenatal exposure to a 900 MHz electromagnetic field on 60-day-old rat testis and epididymal sperm quality.

    Science.gov (United States)

    Odacı, E; Hancı, H; Yuluğ, E; Türedi, S; Aliyazıcıoğlu, Y; Kaya, H; Çolakoğlu, S

    2016-01-01

    We investigated the effects of exposure in utero to a 900 megahertz (MHz) electromagnetic field (EMF) on 60-day-old rat testis and epididymis. Pregnant rats were divided into control (CG; no treatment) and EMF (EMFG) groups. The EMFG was exposed to 900 MHz EMF for 1 h each day during days 13 - 21 of pregnancy. Newborn rats were either newborn CG (NCG) or newborn EMF groups (NEMFG). On postnatal day 60, a testis and epididymis were removed from each animal. Epididymal semen quality, and lipid and DNA oxidation levels, apoptotic index and histopathological damage to the testis were compared. We found a higher apoptotic index, greater DNA oxidation levels and lower sperm motility and vitality in the NEMFG compared to controls. Immature germ cells in the seminiferous tubule lumen, and altered seminiferous tubule epithelium and seminiferous tubule structure also were observed in hematoxylin and eosin stained sections of NEMFG testis. Nuclear changes that indicated apoptosis were identified in TUNEL stained sections and large numbers of apoptotic cells were observed in most of the seminiferous tubule epithelium in the NEMFG. Sixty-day-old rat testes exposed to 900 MHz EMF exhibited altered sperm quality and biochemical characteristics.

  12. Arterial flow regulator enables transplantation and growth of human fetal kidneys in rats.

    Science.gov (United States)

    Chang, N K; Gu, J; Gu, S; Osorio, R W; Concepcion, W; Gu, E

    2015-06-01

    Here we introduce a novel method of transplanting human fetal kidneys into adult rats. To overcome the technical challenges of fetal-to-adult organ transplantation, we devised an arterial flow regulator (AFR), consisting of a volume adjustable saline-filled cuff, which enables low-pressure human fetal kidneys to be transplanted into high-pressure adult rat hosts. By incrementally withdrawing saline from the AFR over time, blood flow entering the human fetal kidney was gradually increased until full blood flow was restored 30 days after transplantation. Human fetal kidneys were shown to dramatically increase in size and function. Moreover, rats which had all native renal mass removed 30 days after successful transplantation of the human fetal kidney were shown to have a mean survival time of 122 days compared to 3 days for control rats that underwent bilateral nephrectomy without a prior human fetal kidney transplant. These in vivo human fetal kidney models may serve as powerful platforms for drug testing and discovery.

  13. Comparative effects of phencyclidine (PCP) and. delta. /sup 9/-tetrahydrocannabinol (THC) on glucose oxidation in the rat testis

    Energy Technology Data Exchange (ETDEWEB)

    Husain, S.; Bauer, V.

    1986-03-05

    Glucose and fructose are important fuels of cellular energetics in organs like testis and brain. The previous in-vitro studies indicated that THC may disrupt many gonadal functions by inhibiting energy metabolism in the testis. PCP is sold on the street as any one of a variety of psychoactive drugs. Most commonly it is misrepresented as THC. Therefore, to compare the effects of PCP and THC on glucose utilization, in-vitro radiorespirometric experiments were conducted in rat testicular tissues. The /sup 14/CO/sub 2/ production from 5.5 mM radiolabelled glucose was followed in the presence and absence of 0.2, 0.1, 0.05, 0.01, 0.005, 0.0025 mM PCP. PCP produced a dose-dependent biphasic effect, stimulating /sup 14/CO/sub 2/ production by 6.2, 17 and 5.8% and then inhibiting it by 13.2, 15.4 and 8.9% with respective concentrations of PCP. This is in contrast to THC which produced a dose-related inhibition of 15.2, 18.1, 20.1 and 25.3% in /sup 14/CO/sub 2/ production with 0.1, 0.2, 0.3 and 0.4 mM THC. These observations are significant due to the possible abuse of PCP together with THC either deliberately or by misrepresentation.

  14. Molecular identity, expression and functional analysis of interleukin-lα and its isoforms in rat testis

    Institute of Scientific and Technical Information of China (English)

    T.Sultana; K.V.Svechnikov; K.Gustafsson; A.Wahlgren; E.Tham; G.Weber; O.Soder

    2004-01-01

    Interleukin-1α(IL-1α) is a proinflammatory cytokine that has also been found to act as a paracrine mediator involved in the regulation of testicular functions. The present review provides an overview of the role of IL-1α in testicular physiology. Bioactive IL-1α isolated from adult rat testis was found to consist of three distinct immunoreactive protein species with apparent sizes of 45, 24 and 19 kDa. These isoforms showed bioactivity in athymocyte proliferation and steroidogenesis assays with different biopotencies. The background of the molecular heterogeneity and processing, secretion and regulation of the isoforms of testicular IL-1α are discussed. All three isoforms have been found to be secreted into the testis tubular lumen and interstitial space. We have provided evidence that IL- 1α is a paracrine factor that may be of importance in, e.g., the regulation of Leydig cell steroidogenesis.Pathophysiologically, testicular IL-1α may contribute to testicular relapse of acute lymphocytic leukemia in boys.

  15. Summary of the HESI consortium studies exploring circulating inhibin B as a potential biomarker of testis damage in the rat.

    Science.gov (United States)

    Chapin, Robert; Weinbauer, Gerhard; Thibodeau, Michael S; Sonee, Manisha; Saldutti, Louise Parks; Reagan, William J; Potter, David; Moffit, Jeffrey S; Laffan, Susan; Kim, James H; Goldstein, Richard A; Erdos, Zoltan; Enright, Brian P; Coulson, Michelle; Breslin, William J

    2013-02-01

    The Developmental and Reproductive Toxicity Technical Committee of the Health and Environmental Sciences Institute hosted a working consortium of companies to evaluate a new commercially available analytic assay for Inhibin B in rat serum or plasma. After demonstrating that the kit was stable and robust, the group performed a series of independent pathogenesis studies (23 different compound/investigator combinations) designed to examine the correlation between the appearance of lesions in the testis and changes in circulating levels of Inhibin B. These studies were reported individually in the previous articles in this series (this issue), and are discussed in this paper. For roughly half of these exposures, lesions appeared well before Inhibin B changed. A few of the studies showed a good correlation between seminiferous tubule damage and reduced circulating Inhibin B levels, while for seven exposures, circulating Inhibin B was reduced with no detectable alteration in testis histology. Whether this indicates a prodromal response or a false-positive signal will require further investigation. These exceptions could plausibly suggest some value of circulating Inhibin B as a useful biomarker in some circumstances. However, for roughly half of these exposures, Inhibin B appeared to be a lagging biomarker, requiring significant damage to the seminiferous tubules before a consistent and credible reduction in circulating levels of Inhibin B was observed.

  16. A Modified Technique for Culturing Primary Fetal Rat Cortical Neurons

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    Sui-Yi Xu

    2012-01-01

    Full Text Available The study explored a modified primary culture system for fetal rat cortical neurons. Day E18 embryos from pregnant Sprague Dawley rats were microdissected under a stereoscope. To minimize enzymatic damage to the cultured neurons, we applied a sequential digestion protocol using papain and Dnase I. The resulting sifted cell suspension was seeded at a density of 50,000 cells per cm2 onto 0.1 mg/mL L-PLL-covered vessels. After a four-hour incubation in high-glucose Dulbecco’s Modified Eagle’s Medium (HG-DMEM to allow the neurons to adhere, the media was changed to neurobasal medium that was refreshed by changing half of the volume after three days followed by a complete medium change every week. The cells displayed progressively robust neurite extension, and nonneuronal-like cells could barely be detected by five days in vitro (DIV; cell growth was still substantial at 14 DIV. Neurons were identified by β-tubulin III immunofluorescence, and neuronal purity within the cultures was assessed at over 95% by both flow cytometry and by dark-field counting of β-tubulin III-positive cells. These results suggest that the protocol was successful and that the high purity of neurons in this system could be used as the basis for generating various cell models of neurological disease.

  17. Conserved and divergent patterns of expression of DAZL, VASA and OCT4 in the germ cells of the human fetal ovary and testis

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    Coutts Shona

    2007-12-01

    Full Text Available Abstract Background Germ cells arise from a small group of cells that express markers of pluripotency including OCT4. In humans formation of gonadal compartments (cords in testis, nests in ovary takes place during the 1st trimester (6–8 weeks gestation. In the 2nd trimester germ cells can enter meiotic prophase in females whereas in males this does not occur until puberty. We have used qRTPCR, Westerns and immunohistochemical profiling to determine which of the germ cell subtypes in the human fetal gonads express OCT4, DAZL and VASA, as these have been shown to play an essential role in germ cell maturation in mice. Results OCT4 mRNA and protein were detected in extracts from both 1st and 2nd trimester ovaries and testes. In ovarian extracts a marked increase in expression of VASA and DAZL mRNA and protein occurred in the 2nd trimester. In testicular extracts VASA mRNA and protein were low/undetectable in 1st trimester and increased in the 2nd trimester whereas the total amount of DAZL did not seem to change. During the 1st trimester, germ cells were OCT4 positive but did not express VASA. These results are in contrast to the situation in mice where expression of Vasa is initiated in Oct4 positive primordial germ cells as they enter the gonadal ridge. In the 2nd trimester germ cells with intense cytoplasmic staining for VASA were present in both sexes; these cells were OCT4 negative. DAZL expression overlapped with both OCT4 and VASA and changed from the nuclear to the cytoplasmic compartment as cells became OCT4-negative. In males, OCT4-positive and VASA-positive subpopulations of germ cells coexisted within the same seminiferous cords but in the ovary there was a distinct spatial distribution of cells with OCT4 expressed by smaller, peripherally located, germ cells whereas DAZL and VASA were immunolocalised to larger (more mature centrally located cells. Conclusion OCT4, DAZL and VASA are expressed by human fetal germ cells but their

  18. Placental transfer of metals of coal fly ash into various fetal organs of rat

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, V.K.; Chauhan, S.S.; Srivastava, P.K.; Shukla, R.R.; Kumar, V.; Misra, U.K. (Delhi Univ. (India). Dept. of Biochemistry)

    1990-03-01

    Fly ash (100 mg/kg body weight) was administered intratracheally to 14-day pregnant rats for 6 consecutive days. On day 20 of gestation the translocation of metals present in the fly ash to various maternal and fetal organs was studied. Fly ash administration to pregnant mothers retarded the growth of fetal heart and kidney as determined by their weights. Fly ash instillation increased organ levels of nearly all the metals studied in both mother and fetus. Most of the metals present in coal fly ash were transferred in significant amounts through placenta to several fetal organs. However, the pattern of their distribution into various fetal organs was different for different metals.

  19. Oncogene-mediated transformation of fetal rat colon in vitro.

    Science.gov (United States)

    Pories, S; Jaros, K; Steele, G; Pauley, A; Summerhayes, I C

    1992-05-01

    Short-term maintenance of fetal rat colonic tissue in vitro has been demonstrated using a collagen matrix organ culture system. The introduction of single (v-myc, v-rasH, v-src) oncogenes or combinations of oncogenes (v-myc/rasH, v-myc/src) into normal colon mucosal elements was established using retroviral vectors, resulting in enhanced proliferation and migration of epithelial cells from the lumen of tissue implants. Expression of a single oncogene in normal colon epithelium did not result in the establishment of cell lines. In contrast, expression of cooperating oncogenic elements resulted in cell lines in greater than 80% of experiments, revealing different morphological characteristics dependent upon the oncogene combination used. Confirmation of the expression of viral transcripts was determined using Northern blot analysis and viral oncoprotein expression using Western blot analysis (p21) and an immunoprecipitation kinase assay (src). Expression of keratin filaments was lost following passaging of cell lines but could be induced by the myc/ras transformants by growth on Rat-1 feeder layers. This induction phenomenon was not observed with myc/src lines, and although these expressed high levels of sucrase isomaltase the epithelial origin of these cells is unclear. Karyotypic analysis performed on three myc/ras-transformed cell lines revealed a normal chromosome complement associated with transformation. In this report we describe a novel in vitro transformation system for normal rat colonic epithelium mediated by the introduction of oncogene elements using different retroviral vector constructs. The potential to generate cell lines representing different stages of neoplastic progression using relevant genetic components presents significant advantages for the study of cellular and molecular interactions underlying colon neoplastic progression.

  20. Effects on rat testis of 1.95-GHz W-CDMA for IMT-2000 cellular phones.

    Science.gov (United States)

    Imai, Norio; Kawabe, Mayumi; Hikage, Takashi; Nojima, Toshio; Takahashi, Satoru; Shirai, Tomoyuki

    2011-08-01

    In recent years concern has arisen whether carrying a cellular phone near the reproductive organs such as the testes may cause dysfunction and particularly decrease in sperm development and production, and thus fertility in men. The present study was performed to investigate the effects of a 1.95 GHz electromagnetic field on testicular function in male Sprague-Dawley rats. Five week old animals were divided into 3 groups of 24 each and a 1.95-GHz wide-band code division multiple access (W-CDMA) signal, which is used for the freedom of mobile multimedia access (FOMA), was employed for whole body exposure for 5 hours per day, 7 days a week for 5 weeks (the period from the age of 5 to 10 weeks, corresponding to reproductive maturation in the rat). Whole-body average specific absorption rates (SAR) for individuals were designed to be 0.4 and 0.08 W/kg respectively. The control group received sham exposure. There were no differences in body weight gain or weights of the testis, epididymis, seminal vesicles, and prostate among the groups. The number of sperm in the testis and epididymis were not decreased in the electromagnetic field (EMF) exposed groups, and, in fact, the testicular sperm count was significantly increased with the 0.4 SAR. Abnormalities of sperm motility or morphology and the histological appearance of seminiferous tubules, including the stage of the spermatogenic cycle, were not observed. Thus, under the present exposure conditions, no testicular toxicity was evident.

  1. Effects of Arctium lappa on Cadmium-Induced Damage to the Testis and Epididymis of Adult Wistar Rats.

    Science.gov (United States)

    Predes, Fabricia de Souza; Diamante, M A S; Foglio, M A; Dolder, H

    2016-10-01

    The protective role of Arctium lappa (AL) on the testes of rats acutely exposed to cadmium (Cd) was tested. The rats were randomly divided into a control group (C-group) and three major experimental groups, which were further subdivided into minor groups (n = 6) according to the experimental period (7 or 56 days). The C-group was subdivided into C-7 and C-56 [receiving a single saline solution, intraperitoneal (i.p.), on the first day]; the AL-group, AL-7, and AL-56, received AL extract (300 mg/kg/daily); the Cd group, Cd-7 and Cd-56, received a single i.p. dose of CdCl2 (1.2 mg/kg body weight (BW)) on the first day; the CdAL group, CdAL-7 and CdAL-56, received the same Cd dose, followed by AL extract. Water or AL extract was administered daily by gavage. After either 7 or 56 days, the testis and accessory glands were removed after whole-body perfusion. Exposure to Cd and CdAL decreased the weight of the testis and epididymis, the gonadosomatic index, seminiferous tubular (ST) diameter, and ST volumetric proportion, and increased the volumetric proportion of interstitium after 56 days. In the epididymis caput, the tubular volumetric proportion decreased along with an increase of interstitial volumetric proportion and epithelium height after 56 days. The alterations observed were less severe only after 7 days. A progressive testicular damage resulted mainly in tubules lined only by Sertoli cells. The sperm number and cell debris decreased in the epididymis. We demonstrated that the testicular damage induced by single acute i.p. exposure to Cd occurred despite the daily oral intake of AL extract.

  2. Improvement of mercuric chloride-induced testis injuries and sperm quality deteriorations by Spirulina platensis in rats.

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    Gaber E El-Desoky

    Full Text Available The present study was undertaken to investigate the protective effect of the filamentous cyanobacterium Spirulina platensis (S. platensis on mercury (II chloride (HgCl(2-induced oxidative damages and histopathological alterations in the testis of Wistar albino rats. The animals were divided into four equal groups, i control, ii HgCl(2, iii S. platensis and iv combination of HgCl(2+S. platensis. Oxidative stress, induced by a single dose of HgCl(2 (5 mg/kg, bw; subcutaneously, s.c., substantially decreased (P<0.01 the activity level of testicular key enzymatic antioxidant biomarkers (superoxide dismutase, SOD; catalase, CAT and glutathione peroxidase, GPx, oxidative stress makers (blood hydroperoxide; testicular reduced glutathione, GSH and malondialdehyde, MDA, and testicular mercury levels. Moreover, HgCl(2 administration resulted in a significant (P<0.01 increase in the number of sperms with abnormal morphology and decrease in epididymal sperm count, motility, plasma testosterone level and testicular cholesterol. Furthermore, HgCl(2 exposure induced histopathological changes to the testis including morphological alterations of the seminiferous tubules, and degeneration and dissociation of spermatogenic cells. Notably, oral pretreatment of animals with Spirulina (300 mg/kg, bw lowered the extent of the observed HgCl(2-mediated toxicity, whereby significantly reducing the resulting lipid peroxidation products, mercury accumulation in the testis, histopathological changes of the testes and spermatozoal abnormalities. In parallel, the pretreatment with Spirulina also completely reverted the observed Hg-Cl(2-induced inhibition in enzymatic activities of antioxidant biomarkers (SOD, CAT and GPx back to control levels. The pretreatment of rats with S. platensis significantly recovered the observed HgCl(2-mediated decrease in the weight of accessory sex organs. Taken together, our findings clearly highlight the role of S. platensis as a protective

  3. Improvement of Mercuric Chloride-Induced Testis Injuries and Sperm Quality Deteriorations by Spirulina platensis in Rats

    Science.gov (United States)

    El-Desoky, Gaber E.; Bashandy, Samir A.; Alhazza, Ibrahim M.; Al-Othman, Zeid A.; Aboul-Soud, Mourad A. M.; Yusuf, Kareem

    2013-01-01

    The present study was undertaken to investigate the protective effect of the filamentous cyanobacterium Spirulina platensis (S. platensis) on mercury (II) chloride (HgCl2)-induced oxidative damages and histopathological alterations in the testis of Wistar albino rats. The animals were divided into four equal groups, i) control, ii) HgCl2, iii) S. platensis and iv) combination of HgCl2+S. platensis. Oxidative stress, induced by a single dose of HgCl2 (5 mg/kg, bw; subcutaneously, s.c.), substantially decreased (P<0.01) the activity level of testicular key enzymatic antioxidant biomarkers (superoxide dismutase, SOD; catalase, CAT and glutathione peroxidase, GPx), oxidative stress makers (blood hydroperoxide; testicular reduced glutathione, GSH and malondialdehyde, MDA), and testicular mercury levels. Moreover, HgCl2 administration resulted in a significant (P<0.01) increase in the number of sperms with abnormal morphology and decrease in epididymal sperm count, motility, plasma testosterone level and testicular cholesterol. Furthermore, HgCl2 exposure induced histopathological changes to the testis including morphological alterations of the seminiferous tubules, and degeneration and dissociation of spermatogenic cells. Notably, oral pretreatment of animals with Spirulina (300 mg/kg, bw) lowered the extent of the observed HgCl2-mediated toxicity, whereby significantly reducing the resulting lipid peroxidation products, mercury accumulation in the testis, histopathological changes of the testes and spermatozoal abnormalities. In parallel, the pretreatment with Spirulina also completely reverted the observed Hg-Cl2-induced inhibition in enzymatic activities of antioxidant biomarkers (SOD, CAT and GPx) back to control levels. The pretreatment of rats with S. platensis significantly recovered the observed HgCl2-mediated decrease in the weight of accessory sex organs. Taken together, our findings clearly highlight the role of S. platensis as a protective modulator of HgCl2

  4. Maternal and fetal metabonomic alterations in prenatal nicotine exposure-induced rat intrauterine growth retardation.

    Science.gov (United States)

    Feng, Jiang-hua; Yan, You-e; Liang, Gai; Liu, Yan-song; Li, Xiao-jun; Zhang, Ben-jian; Chen, Liao-bin; Yu, Hong; He, Xiao-hua; Wang, Hui

    2014-08-25

    Prenatal nicotine exposure causes adverse birth outcome. However, the corresponding metabonomic alterations and underlying mechanisms of nicotine-induced developmental toxicity remain unclear. The aims of this study were to characterize the metabolic alterations in biofluids in nicotine-induced intrauterine growth retardation (IUGR) rat model. In the present study, pregnant Wistar rats were intragastrically administered with different doses of nicotine (0.5, 1.0 and 2.0 mg/kg d) from gestational day (GD) 11-20. The metabolic profiles of the biofluids, including maternal plasma, fetal plasma and amniotic fluid, were analyzed using (1)H nuclear magnetic resonance (NMR)-based metabonomic techniques. Prenatal nicotine exposure caused noticeably lower body weights, higher IUGR rates of fetal rats, and elevated maternal and fetal corticosterone (CORT) levels compared to the controls. The correlation analysis among maternal, fetal serum CORT levels and fetal bodyweight suggested that the levels of maternal and fetal serum CORT presented a positive correlation (r=0.356, n=32, Pfetal (r=-0.639, n=32, Pfetal bodyweight. The fetal metabonome alterations included the stimulation of lipogenesis and the decreased levels of glucose and amino acids. The maternal metabonome alterations involved the enhanced blood glucose levels, fatty acid oxygenolysis, proteolysis and amino acid accumulation. These results suggested that prenatal nicotine exposure is associated with an altered maternal and fetal metabonome, which may be related to maternal increased glucocorticoid level induced by nicotine. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  5. [Postnatal development of zinc levels in the epididymis and testis in rats under normal and experimental conditions].

    Science.gov (United States)

    Delongeas, J L; Hutin, M F; Burnel, D; Grignon, G

    1987-01-01

    Postnatal testicular and epididymal zinc concentration in the rat was investigated by means of differential pulse polarography. The zinc concentration increased gradually from birth to day 90 in the testis and up to day 60-90 in the epididymis with an abrupt increase on day 21. No marked variation in the zinc content was observed all along the epididymal duct. Experimental castration and efferent duct ligation were carried out in order to assess the influence of blood-borne and luminal androgens on epididymal zinc content. In prepubertal rats, unilateral castration and efferent duct ligation did not affect the zinc content of the epididymis. Moreover, zinc concentration was not affected by bilateral castration which induced very low plasma testosterone levels. These results suggested that epididymal zinc content did not depend upon endocrine testicular secretions, especially androgens. On the other hand, in adult rats efferent duct ligation and cryptorchidism resulted in about 50 and 70% reduction, respectively of the testicular and epididymal zinc content. A correlation was found between the absence of testicular fluid and spermatozoa or the alteration of germ cells and the decrease in epididymal and testicular zinc content.

  6. QUANTITATIVE AND STRUCTURAL CHANGES OF TESTIS AND SEMEN QUALITY PARAMETERS CHANGES CAUSED BY PERORAL ADMINISTRATION OF DIAZINON IN RATS

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    Svätoslav Hluchý

    2012-04-01

    Full Text Available The aim of this study was to find the quantitative and structural changes in the rat testis and changes of semen quality after a diazinon administration. METHODS: Rats received diazinon (99% purity in thier drinking water (40 mg.l-1 with free access. Age of rats at the beginning of the experiment was 30 days and experiment lasted for next 90 days. The histological samples were evaluated by histological and morphometric methods in light microscopy and the samples of semen were evaluated with CASA method. RESULTS: Disintergation of cellular associations in the seminiferous epithelium, germ cells evacuation into the tubule lumen and thier necrosis were mostly observed. Rarely vacuolisation and cracks of epithelium and fibrotisation of interstitial tissue were noted. Morphometric methods have shown extension of epithelium (P subcellular structures and their functions may be damaged which can lead to subfertility. Further investigation of diazinon is needed for verification of our hypothesis.doi:10.5219/188

  7. Hepatotoxicity, Nephrotoxicity and Oxidative Stress in Rat Testis Following Exposure to Haloxyfop-p-methyl Ester, an Aryloxyphenoxypropionate Herbicide

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    Ebenezer Tunde Olayinka

    2015-10-01

    Full Text Available Haloxyfop-p-methyl ester (HPME ((R-2-{4-[3-chloro-5-(trifluoromethyl-2-pyridyloxy]phenoxy}propionic acid, is a selective aryloxyphenoxypropionate (AOPP herbicide. It exerts phytotoxicity through inhibition of lipid metabolism and induction of oxidative stress in susceptible plants. This study investigated the toxicological potentials of HPME in rats. Twenty-four male Wistar rats (170–210 g were randomized into four groups (I–IV. Group I (control received 1 mL of distilled water, while animals in Groups II, III and IV received 6.75, 13.5 and 27 mg/kg body weight HPME, respectively, for 21 days. There was a significant (p < 0.05 increase in renal and hepatic function biomarkers (urea, creatinine, total bilirubin, ALP, ALT, AST in the plasma of treated animals compared to control. Levels of testicular antioxidants, ascorbic acid and glutathione, and activities of glutathione-S-transferase, superoxide dismutase and catalase were reduced significantly after 21 days of HPME administration in a dose-dependent manner. The testicular malondialdehyde level increased significantly in the HPME-treated rats relative to the control. A significant decrease in testicular lactate dehydrogenase, acid phosphatase and γ-glutamyl transferase was also observed in HPME-treated animals. Testicular histology revealed severe interstitial edema and sections of seminiferous tubules with necrotic and eroded germinal epithelium in the HPME-treated rats. Overall, data from this study suggest that HPME altered hepatic and renal function and induced oxidative stress and morphological changes in the testis of rats.

  8. Antenatal taurine supplementation increases taurine content in intrauterine growth restricted fetal rat brain tissue.

    Science.gov (United States)

    Li, Fang; Teng, Hui-Yun; Liu, Jing; Wang, Hua-Wei; Zeng, Li; Zhao, Li-Fang

    2014-09-01

    This study aimed to determine the influence of antenatal taurine supplementation on taurine content in the brains of fetal rats with intrauterine growth restriction (IUGR). Experiments were performed at the Central Laboratory of Bayi Children's Hospital Affiliated to Beijing Military General Hospital in China from January to June 2013. Fifteen pregnant rats were randomly divided into three groups: normal controls, an IUGR group and an IUGR + antenatal taurine supplement group (Taurine group) (n = 5). The IUGR model was induced using a low-protein diet throughout gestation. Rats in the taurine group were fed a diet supplemented with 300 mg/kg/day taurine for 12 days after conception until natural delivery. Two fetal rats were randomly selected in every litter, and taurine levels in the brains of rats were detected using high-performance liquid chromatography-mass spectrometry. Results showed that (1) the mean body weight of the fetal rats in the normal control, IUGR and IUGR + antenatal taurine supplement groups was 6.619 ± 0.4132, 4.509 ± 0.454, and 5.176 ± 0.436 g (F = 429.818, P taurine levels in the brains of the fetal rats in the normal control, IUGR and taurine groups were (2.399 ± 0.134) × 10(5), (1.881 ± 0.166) × 10(5) and (2.170 ± 0.191) × 10(5) μg/g (F = 24.828, P taurine levels in IUGR fetal rat brains were lower than in the control animals, and that antenatal taurine supplementation could significantly increase taurine levels in the brains of fetal rats with IUGR.

  9. Pathophysiology of chronic nitric oxide synthase inhibition-induced fetal growth restriction in the rat

    NARCIS (Netherlands)

    Neerhof, M.G.; Synowiec, S.; Khan, S.; Thaete, L.G.

    2011-01-01

    Objective. To evaluate the pathophysiology of chronic nitric oxide synthase (NOS) inhibition-induced fetal growth restriction (FGR) in the rat. Methods. Timed-pregnant rats received L-NAME (2.5 mg/kg/h) with or without endothelin (ET-1) receptor A (ETA) antagonist from day 14 to 21 of gestation. In

  10. Interaction of exposure concentration and duration in determining the apoptosis of testis in rats after cigarette smoke inhalation

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    Lijuan He

    2016-07-01

    Full Text Available The effects of differences in smoke concentration and exposure duration in Sprague Dawley rats to determine variation in type and severity of the testis apoptosis were evaluated. The daily dosages were 10, 20 and 30 non-filter cigarettes for a period of 2, 4, 6, 8 and 12 weeks. Mainstream smoke exposure suppressed body weight gain in all regimens. A dose-related increase in plasma nicotine concentration was observed in smoke-exposed groups for 4, 6, 8 and 12 week regimens. Histopathological examination of the exposed groups showed disturbances in the stages of spermatogenesis, tubules atrophying and these appeared to be dose-related. Cytoplasmic caspase-3 immunostaining was detected both in Sertoli cells and germ cells in smoke-exposure groups. An increase in TUNEL-positive cells of testicular cells was observed after 6 weeks of cigarette exposure. The results indicate that cigarette exposure concentration and duration have interaction effect to induce apoptosis in the rat testes.

  11. High Fat Diet Exposure during Fetal Life Enhances Plasma and Hepatic Omega-6 Fatty Acid Profiles in Fetal Wistar Rats

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    Marlon E. Cerf

    2015-08-01

    Full Text Available Pregnant rats were fed a high fat diet (HFD for the first (HF1, second (HF2, third (HF3 or all three weeks (HFG of gestation. Maintenance on a HFD during specific periods of gestation was hypothesized to alter fetal glycemia, insulinemia, induce insulin resistance; and alter fetal plasma and hepatic fatty acid (FA profiles. At day 20 of gestation, fetal plasma and hepatic FA profiles were determined by gas chromatography; body weight, fasting glycemia, insulinemia and the Homeostasis Model Assessment (HOMA-insulin resistance were also determined. HF3 fetuses were heaviest concomitant with elevated glycemia and insulin resistance (p < 0.05. HFG fetuses had elevated plasma linoleic (18:2 n-6 and arachidonic (20:4 n-6 acid proportions (p < 0.05. In the liver, HF3 fetuses displayed elevated linoleic, eicosatrienoic (20:3 n-6 and arachidonic acid proportions (p < 0.05. HFG fetuses had reduced hepatic docosatrienoic acid (22:5 n-3 proportions (p < 0.05. High fat maintenance during the final week of fetal life enhances hepatic omega-6 FA profiles in fetuses concomitant with hyperglycemia and insulin resistance thereby presenting a metabolically compromised phenotype.

  12. Fetal and maternal effects of continual exposure of rats to 970-MHz circularly polarized microwaves

    Energy Technology Data Exchange (ETDEWEB)

    Berman, E.; Weil, C.; Phillips, P.A.; Carter, H.B.; House, D.E.

    1992-01-01

    Virtually continual exposure to970-MHz microwaves in circularly-polarized waveguides was used to elicit fetal responses in Sprague-Dawley rats during gestation. Two hundred fifty rats were exposed to microwave radiation at whole-body averaged specific absorption rates (SAR) of 0.07, 2.4, or 4.8 W/kg, or concurrently sham-irradiated for 22 h/day from the 1st through the 19th day of gestation. At SAR of 4.8 W/kg, only fetal body weight was significantly altered (-12%, P=.012). Two of twelve rats died during the exposure at SAR of 4.8 W/kg. Bred, but non-pregnant, rats that were exposed at SAR of 4.8 W/kg had significantly lower body weight gain than sham-irradiated rats; similar lower gain is assumed to have occurred in the pregnant rats exposed at SAR of 4.8 W/kg, and whose fetuses were significantly smaller. The authors conclude that continual gestational exposure at SAR of 4.8 (but not 2.4 or lower) W/kg induces fetal alterations. Apparently, deleterious maternal effects are associated with these fetal changes. Although colonic temperature was not measured in these rats, it is expected that exposure at 4.8 W/kg was hyperthermal.

  13. Altered vestibular function in fetal and newborn rats gestated in space

    Science.gov (United States)

    Ronca, A. E.; Alberts, J. R.

    1997-01-01

    Researchers evaluated vestibular development and function in rat pups flown during gestation on the NASA-NIH R1 and R2 missions. Fetal and postnatal vestibular function were examined. Altered vestibular-mediated responses in the experimental fetal pups are attributed to either direct effect of gravity on the vestibular system or indirect effects of microgravity transduced through the mother. The postnatal tests confirmed the hypothesis that the vestibular system continually adapts and responds to tonic stimulation.

  14. Developmental expression of p97/VCP (Valosin-containing protein and Jab1/CSN5 in the rat testis and epididymis

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    Aslan Huseyin

    2011-08-01

    Full Text Available Abstract Background The ubiquitin proteasome system (UPS is a key player in regulating many cellular processes via proteasomal degradation of ubiquitinated proteins. Recently published data show that Jab1/CSN5 interacts with p97/VCP and controls the ubiquitination status of proteins bound to p97/VCP in mouse and human cells. However, coexpression of p97/VCP and Jab1/CSN5 in the developing rat testis and epididymis has not previously been studied. Methods Testicular and epididymal tissues from 5-, 15-, 30-, and 60-day-old rats were examined by immunohistochemistry and Western blotting. Colocalisation of proteins was determined by immunofluorescence microscopy. Results In the 5-day-old rat testis, p97/VCP and Jab1/CSN5 were specifically expressed in gonocytes. The expression of p97/VCP and Jab1/CSN5 significantly increased at day 15 and was found in spermatogonia, Sertoli cells and spermatocytes. In 30- and 60-day-old rat testes, p97/VCP indicated moderate to strong expression in Sertoli cells, spermatogonia, round and elongating spermatids. However, moderate to weak expression was observed in spermatocytes. Jab1/CSN5 showed strong expression in spermatogonia and spermatocytes, while relatively moderate expression was observed in round and elongating spermatids in 30- and 60-day-old rat testes. In contrast, in the epididymis, the expression of both proteins gradually increased from 5 to 60 days of age. After rats reached 2 weeks of age, the expression of both proteins was mostly restricted to the basal and principal cells of the caput epididymis. Conclusions Our study suggests that p97/VCP and Jab1/CSN5 could be an important part of the UPS in the developing rat testis and epididymis and that both proteins may be involved in the regulation of spermatogenesis and epididymal epithelial functions.

  15. Gallic acid protects against cyclophosphamide-induced toxicity in testis and epididymis of rats.

    Science.gov (United States)

    Oyagbemi, A A; Omobowale, T O; Saba, A B; Adedara, I A; Olowu, E R; Akinrinde, A S; Dada, R O

    2016-05-01

    The protective role of gallic acid (GA) on reproductive toxicity induced by cyclophosphamide (CPA), an antineoplastic drug, was investigated in male Wistar rats. Sixty rats were grouped into 10 rats per group. Group 1 (control) received distilled water. Rats in groups 2 and 3 received GA alone at 60 and 120 mg kg(-1) for 14 consecutive days, respectively. Group 4 received a single intraperitoneal dose of CPA at 200 mg kg(-1) on day 1. Groups 5 and 6 received a single dose of CPA (200 mg kg(-1) ) intraperitoneally on day 1 followed by treatment with GA at 60 and 120 mg kg(-1) for 14 consecutive days, respectively. In testes and epididymis of the treated rats, CPA administration resulted in significant elevation (P < 0.05) in malondialdehyde (MDA), nitrite and hydrogen peroxide levels. There was a significant decrease in the activities of superoxide dismutase and glutathione-S-transferase. Furthermore, there were significant reductions in plasma luteinising hormone (LH), follicle stimulation hormone (FSH) and testosterone levels, which were accompanied by significant decrease in sperm motility and viability in CPA-treated rats. Histological examination revealed marked testicular and epididymal atrophy in CPA alone treated rats and these aberrations were reversed by GA. In conclusion, GA has capacity to protect against reproductive toxicity induced by cyclophosphamide.

  16. Effects of melatonin on lipid peroxidation and antioxidant enzymes in streptozotocin-induced diabetic rat testis

    Institute of Scientific and Technical Information of China (English)

    Abdullah Armagan; Efkan Uz; H. Ramazan Yilmaz; Sedat Soyupek; Taylan Oksay; Nurten Ozcelik

    2006-01-01

    Aim: To examine the effects of melatonin treatment on lipid peroxidation (LPO) and the activities of antioxidant enzymes in the testicular tissue of streptozotocin (STZ)-induced diabetic rats. Methods: Twenty-six male rats were randomly divided into three groups as follows: group Ⅰ, control, non-diabetic rats (n = 9); group Ⅱ, STZ-induced,Following 8-week melatonin treatment, all rats were anaesthetized and then were killed to remove testes from the scrotum. Results: As compared to group Ⅰ, in rat testicular tissues of group Ⅱ, increased levels of malondialdehyde (MDA) (P < 0.01) and superoxide dismutase (SOD) (P < 0.01) as well as decreased levels of catalase (CAT) (P < 0.01)and glutathione peroxidase (GSH-Px) (P > 0.05) were found. In contrast, as compared to group Ⅱ, in rat testicular tissues of group Ⅲ, levels of MDA decreased (but this decrease was not significant, P > 0.05) and SOD (P < 0.01) as well as CAT (P < 0.05) increased. GSH-Px was not influenced by any of the treatment. Melatonin did not significantly affect the elevated glucose concentration of diabetic group. At the end of the study, there was no significant difference between the melatonin-treated group and the untreated group by means of body and testicular weight.Conclusion: Diabetes mellitus increases oxidative stress and melatonin inhibits lipid peroxidation and might regulate the activities of antioxidant enzymes of diabetic rat testes.

  17. Nitric Oxide Overproduction Reduces Insulin Secretion from Isolated Islets in Fetal Hypothyroid Rats.

    Science.gov (United States)

    Rouintan, Z; Farrokhfall, K; Karbalaei, N; Ghasemi, A

    2016-02-01

    Thyroid hormones have developmental effects during fetal life. Fetal hypothyroidism leads to glucose intolerance and reduced insulin secretion capacity. Activity of nitric oxide synthases follows a heterogeneous pattern in hypothyroidism. Overactivity of constitutive nitric oxide synthase (NOS), inhibits glucose-stimulated insulin release. The aim of this study was to examine if reduction in insulin secretion in fetal hypothyroidism is due to overproduction of nitric oxide. Pregnant Wistar rats were divided into 2 groups; the experimental group consumed water containing 0.02% of 6-propyl-2-thiouracil till delivery, while the control group consumed tap water. After delivery serum thyroid hormones were measured. Intravenous glucose tolerance test was performed in 6-month old offspring (n=8). After 3 weeks recovery, pancreatic islets were isolated and insulin secretion, inducible and constitutive nitric oxide synthase activity were measured (n=4). Compared to controls, during intravenous glucose tolerance test, fetal hypothyroid rats had high plasma glucose concentration (p=0.003) and low plasma insulin levels (p=0.012) at 5-20 min and their insulin secretion from isolated islets at basal glucose concentration and in the presence of l-arginine was lower. The nitric oxide synthase inhibitor, NG-nitro-l-arginine methyl ester significantly improved insulin secretion in fetal hypothyroid rats at basal glucose concentration and in the presence of l-arginine. The results showed higher NOS activities in fetal hypothyroid rats (constitutive 17.60±1.09 vs. 47.34±4.44 and inducible 4.09±0.96 vs. 19.97±1.14 pmol/min/mg proteins, p=0.002). In conclusion, NO overproduction through NOS participates in decreased insulin secretion in fetal hypothyroid rats.

  18. Gene Expression Profiling in Liver and Testis of Rats to Characterize the Toxicity of Triazole Fungicides

    Science.gov (United States)

    Four triazole fungicides were studied using toxicogenomic techniques to identify potential mechanisms of action. Adult male Sprague-Dawley rats were dosed for 14 days by gavage with fluconazole, myclobutanil, propiconazole, or triadimefon. Following exposure, serum was collected ...

  19. Photoperiodic regulation of testis function in rats: mediation by a circadian mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Nelson, R.J.; Bamat, M.K.; Zucker, I.

    1982-05-01

    Laboratory rats traditionally are classified as nonphotoperiodic because variations in daylength have little or no effect on their gonadal function. After olfactory bulbectomy, however, rats show clear evidence of photoperiodic regulation of the gonads. The present study demonstrates, by means of resonance experiments, that the testicular response to daylength in rats is mediated by a circadian photoperiodic time measurement system similar to that of photoperiodic rodents. Olfactory-bulbectomized rats were maintained in fixed photoperiods in which a 6 h light period was coupled with dark periods of 18, 30, 42, or 54 h; a fifth group was maintained in a 45L:10D photoperiod. Rats from the 6L:30D, 6L:54D and 14L:10D photoperiods had testes and seminal vesicle weights, plasma testosterone titers and spermatogenesis indices indicative of functional reproductive status. Rats exposed to the 6L:18D and 6L:42D photoperiods had reduced testicular and seminal vesicle weights, lower testosterone levels and reduced spermatogenesis. Researchers hypothesize that photo- and nonphotoperiodic rodent species use similar mechanisms for distinguishing long from short photoperiods, but differ in the extent to which discrimination of short daylengths is transduced into altered gonadal activity.

  20. Neonatally Induced Mild Diabetes in Rats and Its Effect on Maternal, Placental, and Fetal Parameters

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    Yuri Karen Sinzato

    2012-01-01

    Full Text Available The aim of this study was to assess placental changes and reproductive outcomes in neonatally induced mild diabetic dams and fetal development in their offspring. At birth, female rats were assigned either to control or diabetic group (100 mg of streptozotocin/Kg, subcutaneously. At adulthood, the female rats were mated. During pregnancy, the blood glucose levels and glucose and insulin tolerance tests were performed. At term, maternal reproductive outcomes, fetal and placental weight, and placental morphology were analyzed. Diabetic rats had smaller number of living fetuses, implantations and corpora lutea, and increased rate of embryonic loss. Placenta showed morphometric alterations in decidua area. Our results showed that mild diabetes was sufficient to trigger alterations in maternal organism leading to impaired decidua development contributing to failure in embryonic implantation and early embryonic losses. Regardless placental decidua alteration, the labyrinth, which is responsible for the maternal-fetal exchanges, showed no morphometric changes contributing to an appropriate fetal development, which was able to maintain normal fetal weight at term in mild diabetic rats. Thus, this experimental model of diabetes induction at the day of birth was more effective to reproduce the reproductive alterations of diabetic women.

  1. EXPERIMENTAL STUDY IN DIFFERENT EXPRESSION ANDORGANIZATION OF COLLAGEN IN SKIN WOUNDS OFADULT AND FETAL RATS

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To observe the spatial and temporal distribution of collagen in fetal and adult rats wounds. Methods The organization of collagen deposition in fetal and adult rats skin wounds were observed by using van Gieson stain. The methods of immunohistochemistry and in situ hybridization were applied to examine collagen type I and Ⅲ peptide and mRNA localization at serial time point during wound healing. Results Collagen type I and III were present in wounds of both fetal and adult rats, but the timing and pattern of collagen deposition varied. In the fetus, collagen was detected by 48h postwounding (PW), but was not present in the adult wounds until 5d PW. By in situ hybridization, signals in the area of the fetal wound were clearly greater and with increased number of cells as compared to that in the adjacent unwounded tissue. Adult rat wounds had evidence in increased signals of procollagen type Ⅰ and Ⅲ production by wound fibroblasts on day 5. Collagen deposited and was arranged in reticular pattern as that of the normal in fetal wounds. While in the adult wounds, collagen de posited in the fashion of coarse bundles. Conclusion Fetal rat wounds appeared to produce collagen mainly by an increased number of fibroblasts in the area of the wound. In contrast, adult rat wounds underwent fibroblast migration and induction of procollagen mRNA synthesis. Our results suggest that the deposition of collagen type Ⅰ and Ⅲ is regulated by their gene expres sion. Collagen type Ⅲ plays an important role in the arrangement of collagen deposition.

  2. Histological and Quantitative Study of the Effect of Eruca Sativa Seed Oil on The Testis of Albino Rat

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    Mona A. R. Salem and Nehal A. Moustafa

    2001-06-01

    Full Text Available Eruca Sativa (E.S or Gargir seed oil is widely used in folk medicine. This study was conducted to investigate its possible effect on male rat fertility. Histological changes of the testis, level of testosterone hormone and sperm count were determined. The results revealed that administration of low dose of E.S. seed oil caused dilatation of the seminiferous tubules, proliferation of spermatogenic cells and increase of its mitotic activity. Increased number of sperms and epididymis weight, elevated level of testosterone hormone and hyperplasia of interstitial Leydig cells have also been noticed. DNA analysis revealed an increase of the percentage of haploid and decrease of diploid and tetraploid cells. Administration of E.S. seed oil at higher dose showed. decreased diameter of the seminiferous tubules, reduced spermatogenic activity and number of sperms . Also testosterone hormone level decreased and the interstitial cells appeared few. DNA analysis showed a reduction of the percentage of the haploid and increase of the percentage of diploid and tetraploid cells.

  3. The Effect of Early Mosquito Insecticides Exposure on Spraque Dawley Rat Testis: A Histopathological Feature Towards Malignancy?

    Science.gov (United States)

    Indah Winarni, Tri; Auzan Aziman, Milzam; Abshar Andar, Anindyo; Pawitra, Ika

    2017-02-01

    The incidence of health problems associated with endocrine-disruption have increased. Many studies suggesting that endocrine disruptor chemicals (EDC) do contribute to cancer through estrogen-related receptors. Many chemicals have EDCs properties including insecticides. Early life exposure to EDCs can increased the risk of testicular cancer have been reported in the last decade. This study was aimed to determine the effect of insecticides exposure on histopathological tumor cell development of germ and Leydig cell. True experiment research design with posttest only control group design was applied. Sprague Dawley (SD) rat (n = 25) were randomly divided into 5 groups (control group, 25 mg β estradiol 3-benzoate, spiral mosquito coil repellent, 3 ml of liquid mosquito repellent, and 4 ml of liquid mosquito repellent). The exposure were administered for 20 days started at aged 3 days. At the age of 100 days (older adult), testis was stained using Hematoxyllin Eosin (HE) and histological features predicting malignancy were observed. The number of tumor cell development in both testicular germ cells and Leydig cells significantly increased in all treated group compared to those of control and the changes towards malignancy were also observed in all treated group. Exposure to mosquito insecticides causes significant changes in testicular germ and Leydig cell histological features that leads to malignancy.

  4. Microelement status changes of rats testis under increased receipts of heavy metals salts

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    Romanyuk A.M.

    2011-01-01

    Full Text Available The results of the study of 128 rats tissue seminal glands. We presented the experimental rats within 48 days received drinking water salts of zinc, copper, iron, manganese, chromium, and lead. The objective was to study the accumulation of zinc, copper, lead, manganese, chromium and iron in the testicular tissue in their alimentary receipt and in a correction by the drug "Tivortin." The spectrophotometry in atomic absorption mode revealed reduced levels of zinc and increased level of other studied trace elements. Accumulation of copper, iron, manganese, chromium and lead in seminal gland tissue is defined within 48 days, copper, lead and chromium exhibit the largest organ tropism.

  5. Effect of behavior training on learning and memory of young rats with fetal growth restriction

    Institute of Scientific and Technical Information of China (English)

    Li Xuelan; Gou Wenli; Huang Pu; Li Chunfang; Sun Yunping

    2008-01-01

    Objective: To investigate the effect of behavior training on the learning and memory of young rats with fetal growth restriction (FGR). Methods: The model of FGR was established by passive smoking method to pregnant rats.The new-born rats were divided into FGR group and normal group, and then randomly subdivided into trained and untrained group respectively. Morris water maze behavior training was performed on postnatal months 2 and 4, then learning and memory abilities of young rats were measured by dark-avoidance testing and step-down testing. Results: In the dark-avoidance and step-down testing, the young rats' performance of FGR group was worse than that of control group, and the trained group was better than the untrained group significantly. Conclusion: FGR young rats have descended learning and memory abilities. Behavior training could improve the young rats' learning and memory abilities, especially for the FGR young rats.

  6. Responses of testis, epididymis, and sperm of pubertal rats exposed to functionalized multiwalled carbon nanotubes.

    Science.gov (United States)

    Farombi, Ebenezer O; Adedara, Isaac A; Forcados, Gilead E; Anao, Osemudiamen O; Agbowo, Agatha; Patlolla, Anita K

    2016-05-01

    The present study investigated the response of testes, epididymides and sperm in pubertal Wistar rats following exposure to 0, 0.25, 0.5, 0.75, and 1.0 mg kg(-1) functionalized multi-walled carbon nanotubes (f-MWCNTs) for 5 days. The results showed that administration of (f-MWCNTs) significantly increased the activities of superoxide dismutase, catalase, and glutathione peroxidase in a dose-dependent manner in both testes and sperm compared with control group. Moreover, the significant decrease in the activity of glutathione-S-transferase and glutathione level was accompanied with significant elevation in the levels of hydrogen peroxide and malondialdehyde in both testes and sperm of (f-MWCNTs)-treated rats. The spermiogram of (f-MWCNTs)-treated rats indicated significant decrease in epididymal sperm number, sperm progressive motility, testicular sperm number and daily sperm production with elevated sperm abnormalities when compared with the control. Exposure to (f-MWCNTs) decreased plasma testosterone level and produced marked morphological changes including decreased geminal epithelium, edema, congestion, reduced spermatogenic cells and focal areas of tubular degeneration in the testes. The lumen of the epididymides contained reduced sperm cells and there was mild to severe hyperplasia epithelial cells lining the duct of the epididymis. Collectively, pubertal exposure of male rats to (f-MWCNTs) elicited oxidative stress response resulting in marked testicular and epididymides dysfunction.

  7. Multi-residue analysis of free and conjugated hormones and endocrine disruptors in rat testis by QuEChERS-based extraction and LC-MS/MS.

    Science.gov (United States)

    Pouech, Charlène; Tournier, Mikaël; Quignot, Nadia; Kiss, Agneta; Wiest, Laure; Lafay, Florent; Flament-Waton, Marie-Magdeleine; Lemazurier, Emmanuel; Cren-Olivé, Cécile

    2012-03-01

    Endocrine disrupting compounds (EDCs) are suspected to be responsible for many disorders of the human reproductive system. To establish a causality relationship between exposure to endocrine disruptors and disease, experiments on animals must be performed with improved or new analytical tools. Therefore, a simple, rapid, and effective multi-residue method was developed for the determination of four steroid hormones (i.e., testosterone, androstenedione, estrone, and estradiol), glucuronide and sulfate conjugates of estrone and estradiol and four endocrine disruptors in rat testis (i.e., bisphenol A, atrazine, and active metabolites of methoxychlor and vinclozolin). The sample preparation procedure was based on the Quick, Easy, Cheap, Effective, Rugged, and Safe (QuEChERS) approach. An analytical method was then developed to quantify these compounds at ultra-trace levels by liquid chromatography coupled to tandem mass spectrometry. The QuEChERS extraction was optimized with regard to the acetonitrile/water ratio used in the extraction step, the choice of the cleanup method and the acetonitrile/hexane ratio used in the cleanup step. The optimized extraction method exhibited recoveries between 89% and 108% for all tested compounds except the conjugates (31% to 58%). The detection limits of all compounds were below 20 ng g(-1) of wet weight of testis. The method was subsequently applied to determine the levels of hormones and EDCs in seven rat testis samples.

  8. Collaborative work to evaluate toxicity on male reproductive organs by repeated dose studies in rats 22). Effects of 2- and 4-week administration of theobromine on the testis.

    Science.gov (United States)

    Funabashi, H; Fujioka, M; Kohchi, M; Tateishi, Y; Matsuoka, N

    2000-10-01

    The effects of theobromine, a xanthine derivative, on the testis were compared between rats dosed for 2 and 4 weeks to determine whether a 2-week dosing period is long enough to detect toxicity. Theobromine was administered orally to male Sprague-Dawley rats at dose levels of 250 and 500 mg/kg for 2 weeks starting at the age of 6 or 8 weeks, and for 4 weeks from the age of 6 weeks. Histopathological examination of reproductive organs revealed toxic findings in the testis at 500 mg/kg after 2 weeks of dosing at both ages, and at 250 and 500 mg/kg after 4 weeks of dosing. The primary findings were degeneration/necrosis and desquamation of spermatids and spermatocytes, vacuolization of seminiferous tubules, and multinucleated giant cell formation. These findings were present mainly in stages I-VI and XII-XIV. From these results, it is concluded that the toxic effects of theobromine on the testis can be detected by repeated dosing for 2 weeks as well as for 4 weeks.

  9. Preventive effects of β-cryptoxanthin against cadmium-induced oxidative stress in the rat testis

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    Xiao-Ran Liu

    2016-01-01

    Full Text Available β-cryptoxanthin (CRY, a major carotenoid of potential interest for health, is obtained naturally from orange vegetables and fruits. A few research studies have reported that CRY could decrease oxidative stress and germ cell apoptosis. The purpose of this study was to examine the effects of CRY on acute cadmium chloride (CdCl 2 -induced oxidative damage in rat testes. For this study, 24 rats were divided into four groups, one of which serves as a control group that received intraperitoneal (i.p. injections of corn oil and physiological saline. The other rats were i.p. injected with CRY (10 μg kg−1 every 8 h, beginning 8 h before CdCl 2 (2.0 mg kg−1 treatment. The pathological and TUNEL findings revealed that CRY ameliorated the Cd-induced testicular histological changes and germ cell apoptosis in the rats. Furthermore, the Cd-induced decrease in the testicular testosterone (T level was attenuated after CRY administration (P < 0.05. The administration of CRY significantly reversed the Cd-induced increases in the lipid peroxide (LPO and malondialdehyde (MDA levels (P < 0.01. The testicular antioxidants superoxide dismutase (SOD, catalase (CAT and glutathione (GSH were decreased by treatment with Cd alone but were restored by CRY co-treatment. These results demonstrated that the application of CRY can enhance the tolerance of rats to Cd-induced oxidative damage and suggest that it has promised as a pharmacological agent to protect against Cd-induced testicular toxicity.

  10. A novel mode-of-action mediated by the fetal muscle nicotinic acetylcholine receptor resulting in developmental toxicity in rats.

    Science.gov (United States)

    Rasoulpour, Reza J; Ellis-Hutchings, Robert G; Terry, Claire; Millar, Neil S; Zablotny, Carol L; Gibb, Alasdair; Marshall, Valerie; Collins, Toby; Carney, Edward W; Billington, Richard

    2012-06-01

    Sulfoxaflor (X11422208), a novel agricultural molecule, induced fetal effects (forelimb flexure, hindlimb rotation, and bent clavicle) and neonatal death in rats at high doses (≥ 400 ppm in diet); however, no such effects occurred in rabbit dietary studies despite achieving similar maternal and fetal plasma exposure levels. Mode-of-action (MoA) studies were conducted to test the hypothesis that the effects in rats had a single MoA induced by sulfoxaflor agonism on the fetal rat muscle nicotinic acetylcholine receptor (nAChR). The studies included cross-fostering and critical windows of exposure studies in rats, fetal ((α1)(2)β1γδ) and adult ((α1)(2)β1δε) rat and human muscle nAChR in vitro agonism experiments, and neonatal rat phrenic nerve-hemidiaphragm contracture studies. The weight of evidence from these studies supported a novel MoA where sulfoxaflor is an agonist to the fetal, but not adult, rat muscle nAChR and that prolonged agonism on this receptor in fetal/neonatal rats causes sustained striated muscle contracture resulting in concomitant reduction in muscle responsiveness to physiological nerve stimulation. Fetal effects were inducible with as little as 1 day of exposure at the end of gestation, but were rapidly reversible after birth, consistent with a pharmacological MoA. With respect to human relevance, sulfoxaflor was shown to have no agonism on human fetal or adult muscle nAChRs. Taken together, the data support the hypothesis that the developmental effects of sulfoxaflor in rats are mediated via sustained agonism on the fetal muscle nAChR during late fetal development and are considered not relevant to humans.

  11. AN EXPERIMENTAL STUDY OF INTRA- UTERINE HEALING OF FETAL RAT WOUNDS

    Institute of Scientific and Technical Information of China (English)

    崔磊; 张群; 钱云良

    2000-01-01

    Objective In order to investigate the fetal scarless wound healing, we developed an in vivo model to observe the process of wound healing occurring in SD-rat fetus. Methods SD-rat fetuses were given full-thickness incisional wounds in the upper lips under ether anesthesia. Wound specimens were removed successively 12,24,48,72h postwounding (PW) from fetus and 1,3,5,7d PW from adult rats for histological examination. Results In the fetus, re-epithelialization of the skin wound was completed by 24h PW, without apparent acute inflammatory response. Regenerated skin wound with normal architecture and elements was completed by 72h postoperation, indistinguishable from the surrounding normal skin. While in the adult rats, the wounds showed an acute inflammatory response resulting in thickened epithelia and scar formation. Conclusion Fetal wound is characterized by rapid and efficient healing without scar formation followed by real skin regeneration.

  12. Fetal Nerve Cell Transplantation in Early Post-Resuscitation Period in Rats

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    Damira Tazhibayeva

    2015-02-01

    Full Text Available Introduction. Fetal cell transplantation is a promising biomedical approach for disease treatment; however, the use of fetal cell therapy is still experimental. This research was deemed a necessity to provide evidence-based research for the application of cell transplantation as a treatment method. The aim of this study was to evaluate the effect of fetal nerve cell transplantation in rat survivors (and non-survivors after clinical death by mechanical asphyxia.Methods. 68 white laboratory rats were divided into two groups of identical age and sex: a control group of 12-month adult male rats (n = 26 and an experimental group (n = 42. Rats were fixed under ether anesthesia. We then blocked the oral and nasal regions with cotton wool soaked in saline solution. A four-minute clinical death though acute mechanical asphyxia was simulated by applying the method of N. Shim. After the 4-minute clinical death, we resuscitated the rats using external cardiac massage and artifical respiration. Suspension of the fetal nerve cells was injected intraperitoneally at 1mm3 per 25g at the time of cardiac activity restoration. Lactate dehydrogenase (LDH and creatine phosphokinase (CPK levels were examined in the homogenate cerebral cortex of reanimated animals. We recorded the survival rate during the post-resuscitation period and analyzed the integrative brain functions using anxiety-phobic status and latent inhibition.Results. After fetal nerve cell transplantation, the enzymatic reactions in the experimental group became normal with a significant decrease in LDH and an increase in CPK levels compared to the control group. In the control group, 10 rats died and 16 lived (62% survival rate, while 7 rats died and 35 lived (83% survival rate in the experimental group during the first 7 days. Rats that did not receive the treatment tended to die sooner than those in the experimental group. As a result of transplantation, the anxiety level in the experimental group

  13. Crataegus Monogyna Aqueous Extract Ameliorates Cyclophosphamide-Induced Toxicity in Rat Testis: Stereological Evidences

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    Hassan Malekinejad

    2012-01-01

    Full Text Available Cyclophosphamide (CP is extensively used as an antineoplastic agent for the treatment of various cancers, as well as an immunosuppressive agent. However, despite its wide spectrum of clinical uses, CP is known to cause several adverse effects including reproductive toxicity. Crataegus monogyna is one of the oldest pharmaceutical plants that have been shown to be cytoprotective by scavenging free radicals. The present study was conducted to assess whether Crataegus monogyna fruits aqueous extract with anti-oxidant properties, could serve as a protective agent against reproductive toxicity during CP treatment in a rat model. Male Wistar rats were categorized into four groups. Two groups of rats were administered CP at a dose of 5 mg in 5 ml saline/kg/day for 28 days by oral gavages. One of these groups received Crataegus monogyna aqueous extract at a dose of 20 mg/kg/day orally four hours after cyclophosphamide administration. A vehicle treated control group and a Crataegus monogyna control group were also included. The CP-treated group showed significant decreases in the body, testes and epididymides weights as well as many histological alterations. Stereological parameters and spermatogenic activities (Sertoli cell, repopulation and miotic indices were also significantly decreased by CP treatment. Notably, Crataegus coadministration caused a partial recovery in above-mentined parameters. These findings indicate that Crataegus monogyna may be partially protective against CP-induced testicular toxicity.

  14. Tamoxifen induced multinucleated cells (symplasts) and distortion of seminiferous tubules in rat testis

    Institute of Scientific and Technical Information of China (English)

    UrbanJ.A.D'Souza

    2003-01-01

    Aim: To evaluate the effect of tamoxifen citrate on male reproductive system of rat. Methods: Groups of male rats were gavaged with tamoxifen at doses of 200 mg.kg·-1.d-1, 400 mg·kg·-1.d-1 or 800 mg.kg-1·d-1 in 0.1 mL olive oil for 10 consecutive days. Controls were treated with 0.1 mL olive oil. Rats were anesthetized and killed on d 3, d 15 or d 35 after the last dose. Testes were collected, processed for paraffin embedding, sectioned at 5μm thickness, stained with H&E and analyzed microscopically. Results: There was a dose-dependent increase in the occurrence of seminiferous tubular distortion with germinal cell sloughing. The highest dose increased the number of multinucleated giant cells on d 3 and d 15. Conclusion: Tamoxifen citrate induces multinucleated giant cells and germinal epithelial sloughing in a dose-dependent manner and these changes are detrimental to male fertility. (Asian J Androl 2003 Sep; 5: 217-220)

  15. Neuroplasticity Changes of Rat Brain by Musical Stimuli during Fetal Period

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    Siamak Sheikhi

    2015-01-01

    Full Text Available Objective: Fetal development of the central nervous system is an important and sensitive stage which is affected by many external and internal stimuli. This study aimed to investigate effect of musical stimuli on fetal rat brain. Materials and Methods: In this experimental study, twelve female Wistar rats were selected and evenly assigned to control and musical groups. The females were mated with a male rat of the same genotype. Musical group was exposed to classic music with 60 dB power for 90 minutes twice per day from 2nd to 20th day of gestation. The control rats were handled similar to the musical group, but were not exposed to music. Before parturition, all the dams were anesthetized, and their blood samples were obtained and used for corticosterone (COS measurement. They were transcardially perfused by electron microscope (EM fixative agent. The fetal brains were extracted intact and used for slice preparation. Horizontal slices were made for electron microscope preparation, and images were taken and analyzed in terms of cell density and morphological changes. Results: EM observation indicated significant morphological difference in cellular and intercellular spaces between the two groups. Music-treated fetuses had significantly higher cell density in parietal cortex and music-treated dams had lower COS level. Conclusion: It was concluded that prenatal music would have a great impact on neuroplasticity of fetal rat brain, at least indirectly. Although the rat fetuses cannot hear until birth, music-induced reduction in COS blood level of dams might be the reason for neuroplasticity of fetal brain.

  16. Relationships between fetal body weight of Wistar rats at term and the extent of skeletal ossification

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    I. Chahoud

    2005-04-01

    Full Text Available We investigated the relationship between fetal body weight at term (pregnancy day 21 and the extent of ossification of sternum, metacarpus, metatarsus, phalanges (proximal, medial and distal of fore- and hindlimbs and cervical and coccygeal vertebrae in Wistar rats. The relationships between fetal body weight and sex, intrauterine position, uterine horn, horn size, and litter size were determined using historical control data (7594 fetuses; 769 litters of untreated rats. Relationships between body weight and degree of ossification were examined in a subset of 1484 historical control fetuses (154 litters which were subsequently cleared and stained with alizarin red S. Fetal weight was independent of horn size, uterine horn side (left or right or intrauterine position. Males were heavier than females and fetal weight decreased with increasing litter size. Evaluation of the skeleton showed that ossification of sternum, metacarpus and metatarsus was extensively complete and independent of fetal weight on pregnancy day 21. In contrast, the extent of ossification of fore- and hindlimb phalanges and of cervical and sacrococcygeal vertebrae was dependent on fetal body weight. The strongest correlation between body weight and degree of ossification was found for hindlimb, medial and proximal phalanges. Our data therefore suggest that, in full-term rat fetuses (day 21, reduced ossification of sternum, metacarpus and metatarsus results from a localized impairment of bone calcification (i.e., a malformation or variation rather than from general growth retardation and that ossification of hindlimb (medial and proximal phalanges is a good indicator of treatment-induced fetal growth retardation.

  17. Cerebellar cytokine expression in a rat model for fetal asphyctic preconditioning and perinatal asphyxia

    DEFF Research Database (Denmark)

    Vlassaks, Evi; Brudek, Tomasz; Pakkenberg, Bente

    2014-01-01

    in saline for 19 min. Pro- and anti-inflammatory cytokine expression were assessed by real-time PCR and immunohistochemistry in cerebella of newborn rats. We found that tumor necrosis factor alpha and interleukin-10 mRNA were increased 12 h after fetal asphyxia, while the inflammatory cytokine response...

  18. Antenatal taurine reduces cerebral cell apoptosis in fetal rats with intrauterine growth restriction*

    Institute of Scientific and Technical Information of China (English)

    Jing Liu; Xiaofeng Wang; Ying Liu; Na Yang; Jing Xu; Xiaotun Ren

    2013-01-01

    From pregnancy to parturition, Sprague-Dawley rats were daily administered a low protein diet to establish a model of intrauterine growth restriction. From the 12th day of pregnancy, 300 mg/kg rine was daily added to food until spontaneous delivery occurred. Brain tissues from normal neo-natal rats at 6 hours after delivery, neonatal rats with intrauterine growth restriction, and neonatal rats with intrauterine growth restriction undergoing taurine supplement were obtained for further experiments. The terminal deoxyribonucleotidyl transferase (TdT)-mediated biotin-16-dUTP nick-end labeling assay revealed that the number of apoptotic cel s in the brain tissue of neonatal rats with intrauterine growth restriction significantly increased. Taurine supplement in pregnant rats reduced cel apoptosis in brain tissue from neonatal rats with intrauterine growth restriction. nohistochemical staining revealed that taurine supplement increased glial cel line-derived neuro-trophic factor expression and decreased caspase-3 expression in the cerebral cortex of intrauterine growth-restricted fetal rats. These results indicate that taurine supplement reduces cel apoptosis through the glial cel line-derived neurotrophic factor-caspase-3 signaling pathway, resulting in a protective effect on the intrauterine growth-restricted fetal rat brain.

  19. Thimet oligopeptidase: similarity to 'soluble angiotensin II-binding protein' and some corrections to the published amino acid sequence of the rat testis enzyme.

    Science.gov (United States)

    McKie, N; Dando, P M; Rawlings, N D; Barrett, A J

    1993-01-01

    The deduced amino acid sequence of pig liver soluble angiotensin II-binding protein [Sugiura, Hagiwara and Hirose (1992) J. Biol. Chem. 267, 18067-18072] is similar over most of its length to that reported for rat testis thimet oligopeptidase (EC 3.4.24.15) by Pierotti, Dong, Glucksman, Orlowski and Roberts [(1990) (Biochemistry 29, 10323-10329]. We have found that homogeneous rat testis thimet oligopeptidase binds angiotensin II with the same distinctive characteristics as the pig liver protein. Analysis of the nucleotide sequences reported for the two proteins pointed to the likelihood that sequencing errors had caused two segments of the amino acid sequence of the rat protein to be translated out of frame, and re-sequencing of selected parts of the clone (kindly provided by the previous authors) confirmed this. The revised deduced amino acid sequence of rat thimet oligopeptidase contains 687 residues, representing a protein of 78,308 Da, and is more closely related to those of the pig liver protein and other known homologues of thimet oligopeptidase than that described previously. Images Figure 1 PMID:8216239

  20. Di-(2 ethylhexyl phthalate and flutamide alter gene expression in the testis of immature male rats

    Directory of Open Access Journals (Sweden)

    Yu Frank H

    2009-09-01

    Full Text Available Abstract We previously demonstrated that the androgenic and anti-androgenic effects of endocrine disruptors (EDs alter reproductive function and exert distinct effects on developing male reproductive organs. To further investigate these effects, we used an immature rat model to examine the effects of di-(2 ethylhexyl phthalate (DEHP and flutamide (Flu on the male reproductive system. Immature male SD rats were treated daily with DEHP and Flu on postnatal days (PNDs 21 to 35, in a dose-dependent manner. As results, the weights of the testes, prostate, and seminal vesicle and anogenital distances (AGD decreased significantly in response to high doses of DEHP or Flu. Testosterone (T levels significantly decreased in all DEHP- treated groups, whereas luteinizing hormone (LH plasma levels were not altered by any of the two treatments at PND 36. However, treatment with DEHP or Flu induced histopathological changes in the testes, wherein degeneration and disorders of Leydig cells, germ cells and dilatation of tubular lumen were observed in a dose-dependent manner. Conversely, hyperplasia and denseness of Leydig, Sertoli and germ cells were observed in rats given with high doses of Flu. The results by cDNA microarray analysis indicated that 1,272 genes were up-regulated by more than two-fold, and 1,969 genes were down-regulated in response to DEHP, Flu or both EDs. These genes were selected based on their markedly increased or decreased expression levels. These genes have been also classified on the basis of gene ontology (e.g., steroid hormone biosynthetic process, regulation of transcription, signal transduction, metabolic process, biosynthetic process.... Significant decreases in gene expression were observed in steroidogenic genes (i.e., Star, Cyp11a1 and Hsd3b. In addition, the expression of a common set of target genes, including CaBP1, Vav2, Plcd1, Lhx1 and Isoc1, was altered following exposure to EDs, suggesting that they may be marker genes to

  1. [Effect of acute alcohol intoxication on lipid peroxidation in testis and adrenal glands of rats].

    Science.gov (United States)

    Khokha, A M; Kashko, M F; Antsulevich, S N; Doroshkevich, N A; Voronov, P P

    1993-01-01

    Hormones level and lipid peroxidation processes under influence of acute alcohol intoxication are tested in testes and adrenals of rats. Ethanol marker effects--the rise of corticosterone biosynthesis and depression of testosterone concentration--were reproduced in the experiment. At the moment of maximal changes in steroid levels indices characterising lipid peroxidation didn't differ from the control. At the early stage of the experiment transient shifts in malonic dialdehyde and dienic conjugates levels were noted. The data obtained does not agree with the hypothesis of acute ethanol effects in testes and adrenals being mediated through the changes of lipid peroxidation rate.

  2. Evaluating the anti-fertility potential of α-chlorohydrin on testis and spermatozoa in the adult male wild Indian house rat (Rattus rattus).

    Science.gov (United States)

    Madhu, Nithar Ranjan; Sarkar, Bhanumati; Biswas, Surjyo Jyoti; Behera, Biplab Kumar; Patra, Ashis

    2011-01-01

    To examine the effects of α-chlorohydrin on testis and cauda epididymis in the male house rat (Rattus rattus), 24 adult male rats were segregated into two groups. Group I rats were force-fed daily by intragastric intubation with α-chlorohydrin at a single dose of 1.0 mg/100 g body weight/d for 5, 15, and 45 days. Another group was fed with distilled water, which served as the control. The treated male rats were paired with 24 adult proestrus female rats for 5 days after the last oral treatment and fertility was tested. At the end of the experiments, all of the male rats were weighed and killed by cervical dislocation. The right testes were removed, weighed, and processed for ultrastructural changes of spermatozoa from the cauda epididymis and testis under scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The seminiferous tubular area, nuclear diameter of the Sertoli and Leydig cells, percentage of spermatogonia, primary spermatocytes, secondary spermatocytes, spermatids, spermatozoa, and Sertoli cells in each group were compared morphometrically. Our results showed that the percentages of primary spermatocytes steadily increased from 5 to 15 days, but primary and secondary spermatocytes decreased significantly at 45 days. There was a steady decline in the percentages of spermatozoa and spermatids at all fixation intervals in the treated animals, but the percentages of spermatogonia and Sertoli cells increased significantly at 15 and 45 days. Seminiferous tubular areas, nuclear diameter of Leydig and Sertoli cells, and fertility rates were reduced after 45 days of treatment. SEM and TEM studies revealed severe morphological abnormalities in the spermatozoa, including deglutination of the acrosomal part, loss of head capsules, and fragmentation of tail fibrils. There was an enhanced anti-fertility effect and a lower number of implantation sites in the rats treated for 5 days. Our results validate α-chlorohydrin as a successful anti

  3. Developmental toxicity of toluene in male rats: effects on semen quality, testis morphology, and apoptotic neurodegeneration

    DEFF Research Database (Denmark)

    Dalgaard, M.; Hossaini, A.; Hougaard, K.S.

    2001-01-01

    , the number of apoptotic cells in the hippocampus and cerebellum were counted after visualisation by means of the TUNEL assay. Mean body weight in pups of exposed darns was lower than in pops from control litters. This decrease was still statistically significant at PND 11, but at PND 21 and 90 the body...... in the toluene-exposed group. Thus, the granular cell layer in cerebellum is a highly relevant tissue with which to study toluene-induced apoptosis, because of the continuous migration of neurons and high frequency of neuronal apoptosis during the weaning period. In summary, it is concluded, that neither pre......- and postnatal exposure to 1200 ppm toluene nor prenatal exposure to 1800 ppm induced significant effects on the reproductive parameters investigated. However, prenatal exposure to 1800 ppm toluene did increase neuronal apoptosis in the cerebellum of weaned male rats, possibly by delaying postnatal migration...

  4. Potential role of estrogen in regulation of the insulin-like growth factor2-H19 locus in the rat testis.

    Science.gov (United States)

    Pathak, Shilpa; D'Souza, Ryan; Ankolkar, Mandar; Gaonkar, Reshma; Balasinor, Nafisa H

    2010-01-15

    The selective estrogen receptor modulator, tamoxifen, has been shown to reduce DNA methylation at Insulin-like growth factor 2/H19 differentially methylated region (Igf2/H19 DMR) in the spermatozoa of the Holtzman rats. Since imprint at this locus is acquired during spermatogenesis in the male germ-line, we hypothesized role for estrogen signaling in the methylation dynamics in the testis. The present study was designed to identify putative estrogen response elements (ERE) at Igf2/H19 DMR and their interaction with DNA methylation pathway. Here, we demonstrate presence of functional ERE at 2637/2655 base pair on Igf2/H19 DMR in testicular germ cells, which was found to bind to estrogen receptor beta (ER beta) in the chromatin immunoprecipitation assay. Tamoxifen attenuated ER beta-ERE association thereby acting as an estrogen antagonist at this locus. Further mechanistic study involving colocalization and immunoprecipitation assay revealed interaction of ER beta and Dnmt1 in the testis. The study provides evidence for the role for estrogen in acquisition of imprint at Igf2/H19 DMR in testis and help in understanding molecular mechanism of environmental estrogens impacting male fertility.

  5. The influence of microwave radiation from cellular phone on fetal rat brain.

    Science.gov (United States)

    Jing, Ji; Yuhua, Zhang; Xiao-qian, Yang; Rongping, Jiang; Dong-mei, Guo; Xi, Cui

    2012-03-01

    The increasing use of cellular phones in our society has brought focus on the potential detrimental effects to human health by microwave radiation. The aim of our study was to evaluate the intensity of oxidative stress and the level of neurotransmitters in the brains of fetal rats chronically exposed to cellular phones. The experiment was performed on pregnant rats exposed to different intensities of microwave radiation from cellular phones. Thirty-two pregnant rats were randomly divided into four groups: CG, GL, GM, and GH. CG accepted no microwave radiation, GL group radiated 10 min each time, GM group radiated 30 min, and GH group radiated 60 min. The 3 experimental groups were radiated 3 times a day from the first pregnant day for consecutively 20 days, and on the 21st day, the fetal rats were taken and then the contents of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), noradrenaline (NE), dopamine (DA), and 5-hydroxyindole acetic acid (5-HT) in the brain were assayed. Compared with CG, there were significant differences (Pcellular phones during pregnancy has certain harm on fetal rat brains.

  6. The Effect of Hydro-Alcoholic Garlic Extract on Testis Weight and Spermatogenesis in Mature Male Rats under Chemotherapy with Cyclophosphamide

    Directory of Open Access Journals (Sweden)

    Marzie Mirfard

    2011-12-01

    Full Text Available Background & Objectives: Cyclophosphamide (with the brand name of Endoxana is an anti-cancer drug used in chemotherapy. The side effects of this drug include anoretic, nausea, decrease in genital gland function, creating amenorrhea, azoospermia and oligospermia. Garlic has been used throughout history as a medicinal drug and a beneficial spice in cooking. The beneficial effects of garlic which have been studied are its anti-oxidant, antibacterial, anti- atherosclerosis, anti-blood platelet effects as well as its role in reducing blood glucose and fat. Garlic has many compounds mostly contain a sulfuric content such as Di-alkyl Di-sulfide (Alicin, Di alyl Di sulfide (DAS, that caused antioxidant and protective properties. Materials & Methods: Cyclophosphamide and garlic extract were given to 56 rats for a period of 28 days. The rats were weighted and after anesthesia, their testis was taken out and tissue dissections were obtained, Student t-test was applied for the statistical analysis. Results: The results show that cyclophosphamide alone leads to a reduction in body and testis weight, and spermatogenesis compared to the control group. In the group that used cyclophosphamide along with garlic extract, as the dose of extract increased, the body and testis weight and spermatogenesis increased in the rats. Conclusion: It seems, the existing compounds in garlic extract can control active metabolites caused by cyclophosphamide and the destructive effect of this drug. Prescribing garlic extract along with cyclophosphamide can possibly be beneficial and effective due to the anti-oxidant characteristics of garlic and also its effect on reducing harmful metabolites.

  7. Aqueous extract of pecan nut shell (Carya illinoensis [Wangenh.] K. Koch) exerts protection against oxidative damage induced by cyclophosphamide in rat testis.

    Science.gov (United States)

    Benvegnu, Dalila M; Barcelos, Raquel C S; Roversi, Katiane; Boufleur, Nardelli; Pase, Camila S; Trevizol, Fabiola; Segat, Hecson J; Dias, Verônica T; Dolci, Geisa S; Antoniazzi, Caren T D; Reckziegel, Patricia; Lima, Fernanda; de Lima, Luiz A R; de Carvalho, Leandro M; da Silva Junior, Valdemiro A; Burger, Marilise E

    2013-01-01

    This study investigated the protective effect of pecan nut (Carya illinoensis) shell aqueous extract (AE) on the oxidative and morphological status of rat testis treated with cyclophosphamide (CP). Wistar rats received water or AE (5%) ad libitum for 37 days. On day 30, half of each group received a single intraperitoneal administration of vehicle or CP 200 mg/kg. After 7 days, the animals were killed and their testis removed. Rats treated with CP presented reduced levels of lactate dehydrogenase, vitamin C, and gluthatione, as well as decreased catalase activity, increased lipid peroxidation levels and superoxide dismutase activity, no alteration in carbonyl protein levels, and a loss of morphological testicular integrity. In contrast, cotreatment with pecan shell AE totally prevented the decrease of lactate dehydrogenase and vitamin C levels and catalase activity and partially prevented the depletion of gluthatione levels. Moreover, it totally prevented the increase in superoxide dismutase activity and lipid peroxidation levels and maintained testicular integrity. These findings show the protective role of pecan shell AE in CP-induced testicular toxicity. The use of this phytotherapy may be considered to minimize deleterious effects related to this chemotherapy.

  8. Necrosis is the dominant cell death pathway in uropathogenic Escherichia coli elicited epididymo-orchitis and is responsible for damage of rat testis.

    Directory of Open Access Journals (Sweden)

    Yongning Lu

    Full Text Available Male infertility is a frequent medical condition, compromising approximately one in twenty men, with infections of the reproductive tract constituting a major etiological factor. Bacterial epididymo-orchitis results in acute inflammation most often caused by ascending canalicular infections from the urethra via the continuous male excurrent ductal system. Uropathogenic Escherichia coli (UPEC represent a relevant pathogen in urogenital tract infections. To explore how bacteria can cause damage and cell loss and thus impair fertility, an in vivo epididymo-orchitis model was employed in rats by injecting UPEC strain CFT073 into the vas deference in close proximity to the epididymis. Seven days post infection bacteria were found predominantly in the testicular interstitial space. UPEC infection resulted in severe impairment of spermatogenesis by germ cell loss, damage of testicular somatic cells, a decrease in sperm numbers and a significant increase in TUNEL (+ cells. Activation of caspase-8 (extrinsic apoptotic pathway, caspase-3/-6 (intrinsic apoptotic pathway, caspase-1 (pyroptosis pathway and the presence of 180 bp DNA fragments, all of which serve as indicators of the classical apoptotic pathway, were not observed in infected testis. Notably, electron microscopical examination revealed degenerative features of Sertoli cells (SC in UPEC infected testis. Furthermore, the passive release of high mobility group protein B1 (HMGB1, as an indication of necrosis, was observed in vivo in infected testis. Thus, necrosis appears to be the dominant cell death pathway in UPEC infected testis. Substantial necrotic changes seen in Sertoli cells will contribute to impaired spermatogenesis by loss of function in supporting the dependent germ cells.

  9. Necrosis is the dominant cell death pathway in uropathogenic Escherichia coli elicited epididymo-orchitis and is responsible for damage of rat testis.

    Science.gov (United States)

    Lu, Yongning; Bhushan, Sudhanshu; Tchatalbachev, Svetlin; Marconi, Marcelo; Bergmann, Martin; Weidner, Wolfgang; Chakraborty, Trinad; Meinhardt, Andreas

    2013-01-01

    Male infertility is a frequent medical condition, compromising approximately one in twenty men, with infections of the reproductive tract constituting a major etiological factor. Bacterial epididymo-orchitis results in acute inflammation most often caused by ascending canalicular infections from the urethra via the continuous male excurrent ductal system. Uropathogenic Escherichia coli (UPEC) represent a relevant pathogen in urogenital tract infections. To explore how bacteria can cause damage and cell loss and thus impair fertility, an in vivo epididymo-orchitis model was employed in rats by injecting UPEC strain CFT073 into the vas deference in close proximity to the epididymis. Seven days post infection bacteria were found predominantly in the testicular interstitial space. UPEC infection resulted in severe impairment of spermatogenesis by germ cell loss, damage of testicular somatic cells, a decrease in sperm numbers and a significant increase in TUNEL (+) cells. Activation of caspase-8 (extrinsic apoptotic pathway), caspase-3/-6 (intrinsic apoptotic pathway), caspase-1 (pyroptosis pathway) and the presence of 180 bp DNA fragments, all of which serve as indicators of the classical apoptotic pathway, were not observed in infected testis. Notably, electron microscopical examination revealed degenerative features of Sertoli cells (SC) in UPEC infected testis. Furthermore, the passive release of high mobility group protein B1 (HMGB1), as an indication of necrosis, was observed in vivo in infected testis. Thus, necrosis appears to be the dominant cell death pathway in UPEC infected testis. Substantial necrotic changes seen in Sertoli cells will contribute to impaired spermatogenesis by loss of function in supporting the dependent germ cells.

  10. Effects of melamine and cyanuric acid on embryo-fetal development in rats.

    Science.gov (United States)

    Kim, Sung-Hwan; Lee, In-Chul; Baek, Hyung-Seon; No, Kyeong-Woo; Shin, Dong-Ho; Moon, Changjong; Kim, Sung-Ho; Park, Seung-Chun; Kim, Jong-Choon

    2013-10-01

    After the outbreak of acute renal failure associated with melamine-contaminated pet food, melamine and melamine-related compounds have become of great interest from a toxicologic perspective. We investigated the potential effects of melamine in combination with cyanuric acid (M + CA, 1:1) on pregnant dams and embryo-fetal development in rats. M + CA was orally administered to pregnant rats from gestational days 6 through 19 at doses of 0, 3, 10, and 30 mg/kg/day of both melamine and cyanuric acid. Maternal toxicity of rats administered 30 mg/kg/day M + CA was manifested as increased incidences of clinical signs and death; gross pathologic findings; higher blood urea nitrogen and creatinine levels; lower body weight gain and food intake; decreased thymus weight; and increased heart, lung, and kidney weights. Histopathological examinations revealed an increase in the incidence of congestion, tubular necrosis/degeneration, crystals, casts, mineralization, inflammatory cells in tubules, tubular dilation, and atrophy of glomeruli in maternal kidneys, whereas fetal kidneys did not show any histopathological changes. Developmental toxicity included a decrease in fetal (28%) and placental weights and a delay in fetal ossification (n = 7). Increased incidence of gross and histopathological changes in the maternal kidney was also found in the middle dose group (n = 12). No treatment-related maternal or developmental effects were observed in the low dose group (n = 12). Under these experimental conditions, M + CA is embryotoxic at an overt maternotoxic dose in rats and the no-observed-adverse-effect level of M + CA is considered to be 3 mg/kg/day for pregnant dams and 10 mg/kg/day for embryo-fetal development.

  11. Finding maximal transcriptome differences between reprotoxic and non-reprotoxic phthalate responses in rat testis.

    Science.gov (United States)

    Yuan, Xiaolian; Jonker, Martijs J; de Wilde, Jillian; Verhoef, Aart; Wittink, Floyd R A; van Benthem, Jan; Bessems, Jos G; Hakkert, Betty C; Kuiper, Raoul V; van Steeg, Harry; Breit, Timo M; Luijten, Mirjam

    2011-07-01

    The chemical legislation of the EU, Registration, Evaluation, and Authorization of Chemicals (REACH), stipulates that about 30 000 chemical substances are to be assessed on their possible risks. Toxicological evaluation of these compounds will at least partly be based on animal testing. In particular, the assessment of reproductive toxicity is a very complicated, time-consuming and animal-demanding process. Introducing microarray-based technologies can potentially refine in vivo toxicity testing. If compounds of a distinct chemical class induce reproducible gene-expression responses with a recognizable overlap, these gene-expression signatures may indicate intrinsic features of certain compounds, including specific toxicity. In the present study, we have set out the first steps towards this approach for the reproductive toxicity of phthalates. Male rats were treated with a single dose of either reprotoxic or non-reprotoxic phthalates, and were analyzed 24 h afterwards. Subsequently, histopathological and gene-expression profiling analyses were performed. Despite ambiguous histopathological observations, we were able to identify genes with differential expression profiles between the reprotoxic phthalates and the non-reprotoxic counterparts. This shows that differences in gene-expression profiles, indicative of the type of exposure, may be detected earlier, or at lower doses, than classical pathological endpoints. These findings are promising for 'early warning' biomarker analyses and for using toxicogenomics in a category approach. Ultimately, this could lead to a more cost-effective approach for prioritizing the toxicity testing of large numbers of chemicals in a short period of time in hazard assessment of chemicals, which is one of the objectives of the REACH chemical legislation.

  12. Effect of Fetal Hypothyroidism on Cardiac Myosin Heavy Chain Expression in Male Rats

    Directory of Open Access Journals (Sweden)

    Nasibeh Yousefzadeh

    2016-01-01

    Full Text Available Abstract Background: Thyroid hormone deficiency during fetal life could affect the cardiac function in later life. The mechanism underlying this action in fetal hypothyroidism (FH in rats has not been elucidated thus far. Objective: The aim of this study is to evaluation the effect of FH on cardiac function in male rats and to determine the contribution of α-myosin heavy chain (MHC and β-MHC isoforms. Methods: Six pregnant female rats were randomly divided into two groups: The hypothyroid group received water containing 6-propyl-2-thiouracil during gestation and the controls consumed tap water. The offspring of the rats were tested in adulthood. Hearts from the FH and control rats were isolated and perfused with langendroff setup for measuring hemodynamic parameters; also, the heart mRNA expressions of α- MHC and β-MHC were measured by qPCR. Results: Baseline LVDP (74.0 ± 3.1 vs. 92.5 ± 3.2 mmHg, p < 0.05 and heart rate (217 ± 11 vs. 273 ± 6 beat/min, p < 0.05 were lower in the FH rats than controls. Also, these results showed the same significance in ±dp/dt. In the FH rats, β-MHC expression was higher (201% and α- MHC expression was lower (47% than control. Conclusion: Thyroid hormone deficiency during fetal life could attenuate normal cardiac functions in adult rats, an effect at least in part due to the increased expression of β-MHC to α- MHC ratio in the heart.

  13. Effect of Fetal Hypothyroidism on Cardiac Myosin Heavy Chain Expression in Male Rats

    Science.gov (United States)

    Yousefzadeh, Nasibeh; Jeddi, Sajad; Alipour, Mohammad Reza

    2016-01-01

    Background: Thyroid hormone deficiency during fetal life could affect the cardiac function in later life. The mechanism underlying this action in fetal hypothyroidism (FH) in rats has not been elucidated thus far. Objective: The aim of this study is to evaluation the effect of FH on cardiac function in male rats and to determine the contribution of α-myosin heavy chain (MHC) and β-MHC isoforms. Methods: Six pregnant female rats were randomly divided into two groups: The hypothyroid group received water containing 6-propyl-2-thiouracil during gestation and the controls consumed tap water. The offspring of the rats were tested in adulthood. Hearts from the FH and control rats were isolated and perfused with langendroff setup for measuring hemodynamic parameters; also, the heart mRNA expressions of α- MHC and β-MHC were measured by qPCR. Results: Baseline LVDP (74.0 ± 3.1 vs. 92.5 ± 3.2 mmHg, p < 0.05) and heart rate (217 ± 11 vs. 273 ± 6 beat/min, p < 0.05) were lower in the FH rats than controls. Also, these results showed the same significance in ±dp/dt. In the FH rats, β-MHC expression was higher (201%) and α- MHC expression was lower (47%) than control. Conclusion: Thyroid hormone deficiency during fetal life could attenuate normal cardiac functions in adult rats, an effect at least in part due to the increased expression of β-MHC to α- MHC ratio in the heart. PMID:27411095

  14. N-Methyl-D-aspartate Receptor Excessive Activation Inhibited Fetal Rat Lung Development In Vivo and In Vitro

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    Zhengchang Liao

    2016-01-01

    Full Text Available Background. Intrauterine hypoxia is a common cause of fetal growth and lung development restriction. Although N-methyl-D-aspartate receptors (NMDARs are distributed in the postnatal lung and play a role in lung injury, little is known about NMDAR’s expression and role in fetal lung development. Methods. Real-time PCR and western blotting analysis were performed to detect NMDARs between embryonic days (E 15.5 and E21.5 in fetal rat lungs. NMDAR antagonist MK-801’s influence on intrauterine hypoxia-induced retardation of fetal lung development was tested in vivo, and NMDA’s direct effect on fetal lung development was observed using fetal lung organ culture in vitro. Results. All seven NMDARs are expressed in fetal rat lungs. Intrauterine hypoxia upregulated NMDARs expression in fetal lungs and decreased fetal body weight, lung weight, lung-weight-to-body-weight ratio, and radial alveolar count, whereas MK-801 alleviated this damage in vivo. In vitro experiments showed that NMDA decreased saccular circumference and area per unit and downregulated thyroid transcription factor-1 and surfactant protein-C mRNA expression. Conclusions. The excessive activation of NMDARs contributed to hypoxia-induced fetal lung development retardation and appropriate blockade of NMDAR might be a novel therapeutic strategy for minimizing the negative outcomes of prenatal hypoxia on lung development.

  15. Antenatal taurine supplementation for improving brain ultrastructure in fetal rats with intrauterine growth restriction.

    Science.gov (United States)

    Liu, J; Liu, L; Chen, H

    2011-05-05

    Changes in brain ultrastructure of fetal rats with intrauterine growth restriction (IUGR) were explored and the effects of antenatal taurine supplementation on their brain ultrastructure were determined. Fifteen pregnant rats were randomly divided into three groups: control group, IUGR model group and IUGR group given antenatal taurine supplements. Taurine was added to the diet of the taurine group at a dose of 300 mg/kg/d from 12 days after conception until natural delivery. Transmission electron microscopy was used to observe ultrastructural changes in the brains of the newborn rats. At the same time, brain cellular apoptosis was detected using TUNEL, and the changes in protein expression of neuron specific enolase and glial fibrillary acidic protein were analyzed using immunohistochemistry. The results showed that: 1) The average body weight and cerebral weight were significantly lower in the IUGR group than in the control group (ptaurine was supplemented (ptaurine supplementation. 3) The results of TUNEL showed that the counts of apoptotic brain cells in IUGR groups were significantly increased from those in control groups and that taurine could significantly decrease brain cell apoptosis (ptaurine-supplementation could significantly increase the counts of neuron specific enolase and glial fibrillary acidic protein immunoreactive cells in fetal rats with IUGR (ptaurine can significantly improve the IUGR fetal brain development.

  16. Maternal endotoxemia, fetal anomalies, and central nervous system damage: a rat model of a human problem.

    Science.gov (United States)

    Ornoy, A; Altshuler, G

    1976-01-15

    Endotoxemia is a common consequence of the gram-negative urinary tract infections that complicate human pregnancies. Only rarely, however, have the effects of maternal endotoxemia been evaluated by animal experiments or by human investigations. Data of the Collaborative Perinatal Study suggest an association between maternal endotoxemia and fetal central nervous system damage. For these reasons we performed controlled studies of the fetal effects of treatment of pregnant rats, at appropriate gestational ages, with E. coli endotoxin. We found a maximum 7 per cent incidence of fetal anomalies in the treated animals but no anomalies in controls. Placental light microscopy examinations indicated the mechanism to include Shwartzman-lixemia produces periventricular leukomalacia. We obtained an incidence of neuronal necrosis in treated fetuses that was 10 times greater than in control fetuses. It is therefore of importance that additional studies of the pathologic effects of endotoxin be performed.

  17. Transcription of the rat testis-specific Rtdpoz-T1 and -T2 retrogenes during embryo development: co-transcription and frequent exonisation of transposable element sequences

    Directory of Open Access Journals (Sweden)

    Chang Che-Ming

    2009-07-01

    Full Text Available Abstract Background Retrotransposition is an important evolutionary force for the creation of new and potentially functional intronless genes which are collectively called retrogenes. Many retrogenes are expressed in the testis and the gene products have been shown to actively participate in spermatogenesis and other unique functions of the male germline. We have previously reported a cluster of retrogenes in the rat genome that encode putative TRAF- and POZ-domain proteins. Two of the genes, Rtdpoz-T1 and -T2 (abbreviated as T1 and T2, have further been shown to be expressed specifically in the rat testis. Results We show here that the T1 and T2 genes are also expressed in the rat embryo up to days 16–17 of development when the genes are silenced until being re-activated in the adult testis. On database interrogation, we find that some T1/T2 exons are chromosomally duplicated as cassettes of 2 or 3 exons consistent with retro-duplication. The embryonic T1/T2 transcripts, characterised by RT-PCR-cloning and rapid amplification of cDNA ends, are further found to have acquired one or more noncoding exons in the 5'-untranslated region (5'-UTR. Most importantly, the T1/T2 locus is embedded within a dense field of relics of transposable element (TE derived mainly from LINE1 and ERV sequences, and the TE sequences are frequently exonised through alternative splicing to form the 5'-UTR sequences of the T1/T2 transcripts. In a case of T1 transcript, the 3'-end is extended into and terminated within an L1 sequence. Since the two genes share a common exon 1 and are, therefore, regulated by a single promoter, a T2-to-T1 co-transcription model is proposed. We further demonstrate that the exonised 5'-UTR TE sequences could lead to the creation of upstream open reading frames resulting in translational repression. Conclusion Exonisation of TE sequences is a frequent event in the transcription of retrogenes during embryonic development and in the testis and

  18. Expression of co-stimulatory molecules, chemokine receptors and proinflammatory cytokines in dendritic cells from normal and chronically inflamed rat testis.

    Science.gov (United States)

    Rival, Claudia; Guazzone, Vanesa A; von Wulffen, Werner; Hackstein, Holger; Schneider, Eva; Lustig, Livia; Meinhardt, Andreas; Fijak, Monika

    2007-12-01

    The presentation of self antigens by dendritic cells (DC) plays an important role in the initiation and maintenance of autoimmunity. In a model of experimental autoimmune orchitis (EAO), we have previously characterized dominant testicular autoantigens and shown an increase in DC numbers during the course of disease. In this study, we have developed a protocol for the isolation of a highly pure population of DC ( approximately 97%) from the testis of EAO and control rats to analyse the expression of major histocompatibility complex (MHC) class II and co-stimulatory molecules (CD80, CD86), chemokine receptors (CCR2, CCR7) and cytokines (IL-10, IL-12p70, TNF-alpha). By flow cytometry, we observed similar percentage and intensity levels of MHC class II, CD80 and CD86 expression in testicular DC in all groups. Moreover, by real-time RT-PCR we have detected significantly higher CCR7 mRNA level in isolated testicular DC from rats with EAO compared to controls, whereas the expression of CCR2 was decreased in orchitis. Transcripts of IL-12p40 were observed in DC from all groups, whereas the expression of IL-10 and the rate limiting IL-12 subunit p35 were detectable exclusively in testicular DC from the inflamed testes. In co-culture experiments, testicular DC isolated from EAO animals significantly enhanced naïve T-cell proliferation compared with control DC. Taken together these results suggest that testicular DC in control testis is not mature and functionally tolerogenic, whereas in EAO testis, IL-12 expression and stimulation of T-cell proliferation points to a mature immunogenic state prior imminent migration to the lymph nodes to amplify immune responses against testicular antigens.

  19. Maternal hypoxia alters matrix metalloproteinase expression patterns and causes cardiac remodeling in fetal and neonatal rats.

    Science.gov (United States)

    Tong, Wenni; Xue, Qin; Li, Yong; Zhang, Lubo

    2011-11-01

    Fetal hypoxia leads to progressive cardiac remodeling in rat offspring. The present study tested the hypothesis that maternal hypoxia results in reprogramming of matrix metalloproteinase (MMP) expression patterns and fibrillar collagen matrix in the developing heart. Pregnant rats were treated with normoxia or hypoxia (10.5% O(2)) from day 15 to 21 of gestation. Hearts were isolated from 21-day fetuses (E21) and postnatal day 7 pups (PD7). Maternal hypoxia caused a decrease in the body weight of both E21 and PD7. The heart-to-body weight ratio was increased in E21 but not in PD7. Left ventricular myocardium wall thickness and cardiomyocyte proliferation were significantly decreased in both fetal and neonatal hearts. Hypoxia had no effect on fibrillar collagen content in the fetal heart, but significantly increased the collagen content in the neonatal heart. Western blotting revealed that maternal hypoxia significantly increased collagen I, but not collagen III, levels in the neonatal heart. Maternal hypoxia decreased MMP-1 but increased MMP-13 and membrane type (MT)1-MMP in the fetal heart. In the neonatal heart, MMP-1 and MMP-13 were significantly increased. Active MMP-2 and MMP-9 levels and activities were not altered in either fetal or neonatal hearts. Hypoxia significantly increased tissue inhibitors of metalloproteinase (TIMP)-3 and TIMP-4 in both fetal and neonatal hearts. In contrast, TIMP-1 and TIMP-2 were not affected. The results demonstrate that in utero hypoxia reprograms the expression patterns of MMPs and TIMPs and causes cardiac tissue remodeling with the increased collagen deposition in the developing heart.

  20. Comparison of the disposition of diethylstilbestrol and estradiol in the fetal rat. Correlation with teratogenic potency.

    Science.gov (United States)

    Henry, E C; Miller, R K

    1986-06-15

    The dispositions of radiolabeled diethylstilbestrol (DES) and estradiol (E2) in the fetal rat were compared to determine whether kinetic differences accounted for their differences in teratogenic potency. 14C (from DES) was concentrated in fetal tissues relative to plasma, whereas 3H (from E2) was largely retained protein-bound in fetal plasma. Both compounds were rapidly metabolized in the fetus (and mother) to less or non-estrogenic products. Fetal levels of E2 declined faster than those of DES (E1 was the primary circulating estrogen within 1-3 hr of E2 injection) so that exposure to unchanged DES was of longer duration than to E2. The unchanged compounds were retained longer and at higher concentrations in the target genital tissue compared to other tissues. Although these differences were consistent with the potencies, the concentration of the unchanged estrogen in fetal genital tract was lower after a teratogenic dose of DES than after a threshold teratogenic dose of E2. However, the 3H in fetal plasma and genital tract cytosol at 1 hr after injection of [3H]E2 at 2 ng or 10 micrograms/fetus was found to be highly protein-bound. DES competed poorly for these binding sites. It is suggested that the concentration of E2 which is "free" in the cell (as DES is), rather than the total content, correlates with its teratogenicity. Thus, in the rat, rapid metabolism and extensive protein-binding, both extra- and intracellularly, reduce the teratogenicity of the natural estrogen compared to the synthetic estrogen.

  1. The effect of copper deficiency on fetal growth and liver anti-oxidant capacity in the Cohen diabetic rat model

    Energy Technology Data Exchange (ETDEWEB)

    Ergaz, Zivanit, E-mail: zivanit@hadassah.org.il [Hebrew University Hadassah Medical School, Jerusalem (Israel); Shoshani-Dror, Dana [Hebrew University Hadassah Medical School, Jerusalem (Israel); Guillemin, Claire [Department of Pharmacology and Therapeutics, McGill University, Montreal (Canada); Neeman-azulay, Meytal; Fudim, Liza [Hebrew University Hadassah Medical School, Jerusalem (Israel); Weksler-Zangen, Sarah [Diabetes Research Unit, Hebrew University Hadassah Medical School and Hospital, Jerusalem (Israel); Stodgell, Christopher J.; Miller, Richard K. [Department of Obstetrics and Gynecology, University of Rochester, Rochester, MN (United States); Ornoy, Asher [Hebrew University Hadassah Medical School, Jerusalem (Israel)

    2012-12-01

    High sucrose low copper diet induces fetal growth restriction in the three strains of the Cohen diabetic rats: an inbred copper deficient resistant (CDr), an inbred copper deficient sensitive (CDs that become diabetic on high sucrose low copper diet -HSD) and an outbred Wistar derived Sabra rats. Although those growth restricted fetuses also exhibit increased oxidative stress, antioxidants do not restore normal growth. In the present study, we evaluated the role of copper deficiency in the HSD induced fetal growth restriction by adding to the drinking water of the rats 1 ppm or 2 ppm of copper throughout their pregnancy. Fetal and placental growth in correlation with fetal liver copper content and anti-oxidant capacity was evaluated on day 21 of pregnancy. HSD compared to regular chow induced fetal growth restriction, which was most significant in the Cohen diabetic sensitive animals. The addition of 1 ppm and 2 ppm copper to the drinking water normalized fetal growth in a dose dependent manner and reduced the degree of hyperglycemia in the diabetes sensitive rats. The CDs fetuses responded to the HSD with lower catalase like activity, and less reduced superoxide dismutase levels compared to the Sabra strain, and had high malondialdehyde levels even when fed regular chow. Immunostaining was higher for nitrotyrosine among the CDr and higher for hypoxia factor 1 α among the CDs. We conclude that in our model of dietary-induced fetal growth restriction, copper deficiency plays a major etiologic role in the decrease of fetal growth and anti-oxidant capacity. -- Highlights: ► High sucrose low copper diet restricted fetal growth in the Cohen diabetic rat model ► Maternal copper blood levels directly correlated with fetal liver copper content ► Copper supplementation decreased embryonic resorption in the inbred strains ► Copper supplementation reduced hyperglycemia in the sucrose sensitive inbred strain ► Copper supplementation alleviated growth restriction and

  2. Maternal-fetal hepatic and placental metabolome profiles are associated with reduced fetal growth in a rat model of maternal obesity

    DEFF Research Database (Denmark)

    Mumme, Karen; Gray, Clint; Reynolds, Clare M.

    2016-01-01

    : Metabolomic profiling was used to reveal altered maternal and fetal metabolic pathways in a model of diet induced obesity during pregnancy, leading to reduced fetal growth. Methods: We examined the metabolome of maternal and fetal livers, and placenta following a high fat and salt intake. Sprague–Dawley rats...... were assigned to (a) control diet (CD; 1 % salt, 10 % kcal from fat), (b) high salt diet (SD; 4 % salt, 10 % kcal from fat), (c) high fat diet (HF; 1 % salt, 45 % kcal from fat) or (d) high-fat high-salt diet (HFSD; 4 % salt, 45 % kcal from fat) 21 days prior to pregnancy and during gestation......Introduction: Maternal obesity is associated with a range of pregnancy complications, including fetal growth restriction (FGR), whereby a fetus fails to reach its genetically determined growth. Placental insufficiency and reduced nutrient transport play a role in the onset of FGR. Objectives...

  3. Angiotensin converting enzyme in the testis and epididymis of mammals.

    Science.gov (United States)

    Jaiswal, A; Joshi, P; Kumar, M V; Panda, J N; Singh, L N

    1984-01-01

    Angiotensin converting enzyme (ACE) activity has been reported in testis and epididymis of seven different animal species. Among all the species, the mouse testis and epididymis showed the highest converting enzyme activity followed by rat testis and epididymis. The lowest activity was detected in buffalo testis and rabbit epididymis. Most of the testicular enzyme was found concentrated in the 107,00 X g sediment while the epididymal enzyme was equally distributed between sediment and supernatant. ACE levels of different regions of the rat testis and epididymis was analyzed. The gradient of ACE was found increasing from caput to cauda. A major fraction of testicular and epididymal ACE activity was found in their respective fluid. ACE appeared only in mature rats, rabbits and mice testis and epididymis. Sexually stimulated rabbits showed significant ACE increase in the testis. In vitro characterization studies were conducted.

  4. Stimulation of DNA and Collagen Synthesis by Autologous Growth Factor in Cultured Fetal Rat Calvaria

    Science.gov (United States)

    Canalis, Ernesto; Peck, William A.; Raisz, Lawrence G.

    1980-11-01

    Conditioned medium derived from organ or cell cultures prepared from 19- to 21-day fetal rat calvaria stimulated the incorporation of [3H]proline into collagen and of [3H]thymidine into DNA in organ cultures of the same tissue. Addition of cortisol enhanced the effect on collagen but not on DNA synthesis. These effects appeared to be due to a nondialyzable and heat-stable growth factor.

  5. Effect of 1α,25-dihydroxyvitamin D3 in plasma membrane targets in immature rat testis: ionic channels and gamma-glutamyl transpeptidase activity.

    Science.gov (United States)

    Zanatta, Leila; Zamoner, Ariane; Gonçalves, Renata; Zanatta, Ana Paula; Bouraïma-Lelong, Hélène; Bois, Camille; Carreau, Serge; Silva, Fátima Regina Mena Barreto

    2011-11-01

    1α,25-Dihydroxyvitamin D(3) (1,25D(3)) is critical for the maintenance of normal reproduction since reduced fertility is observed in vitamin D-deficient male rats. The aim of this study was to investigate the effect of 1,25D(3) in 30-day-old rat testicular plasma membrane targets (calcium uptake and gamma-glutamyl transpeptidase (GGTP) activity), as well as to highlight the role of protein kinases in the mechanism of action of 1,25D(3). The results demonstrated that 1,25D(3) induced a fast increase in calcium uptake in rat testis through a nongenomic mechanism of action. This effect was dependent on PKA, PKC and MEK. Moreover, ionic channels, such as ATP- and Ca(2+)-dependent K(+) channels and Ca(2+)-dependent Cl(-) channels, are involved in the mechanism of action. The use of BAPTA-AM showed that [Ca(2+)](i) was also implicated, and the incubation with digoxin produced an increase in (45)Ca(2+) uptake indicating that the effect of 1,25D(3) may also result from Na(+)/K(+)-ATPase inhibition. In addition, 1,25D(3) was able to increase the GGTP activity. Considered together, our results indicate a PKA/PKC/MEK-dependent 1,25D(3) pathway as well as ionic involvement leading to (45)Ca(2+) uptake in immature rat testis. These findings demonstrate that 1,25D(3) stimulates calcium uptake and increases GGTP activity which may be involved in male reproductive functions.

  6. Moderate Exercise Attenuates Lipopolysaccharide-Induced Inflammation and Associated Maternal and Fetal Morbidities in Pregnant Rats.

    Directory of Open Access Journals (Sweden)

    Karina T Kasawara

    Full Text Available Fetal growth restriction (FGR and coagulopathies are often associated with aberrant maternal inflammation. Moderate-intensity exercise during pregnancy has been shown to increase utero-placental blood flow and to enhance fetal nutrition as well as fetal and placental growth. Furthermore, exercise is known to reduce inflammation. To evaluate the effect of moderate-intensity exercise on inflammation associated with the development of maternal coagulopathies and FGR, Wistar rats were subjected to an exercise regime before and during pregnancy. To model inflammation-induced FGR, pregnant rats were administered daily intraperitoneal injections of E. coli lipopolysaccharide (LPS on gestational days (GD 13.5-16.5 and sacrificed at GD 17.5. Control rats were injected with saline. Maternal hemostasis was assessed by thromboelastography. Moderate-intensity exercise prevented LPS-mediated increases in white blood cell counts measured on GD 17.5 and improved maternal hemostasis profiles. Importantly, our data reveal that exercise prevented LPS-induced FGR. Moderate-intensity exercise initiated before and maintained during pregnancy may decrease the severity of maternal and perinatal complications associated with abnormal maternal inflammation.

  7. Effect of water temperature on exercise-induced maternal hyperthermia on fetal development in rats.

    Science.gov (United States)

    Mottola, M F; Fitzgerald, H M; Wilson, N C; Taylor, A W

    1993-07-01

    The objective of this study was to determine if water temperature influenced exercise-induced hyperthermia in swim-trained pregnant rats and the resulting fetal development. Pregnant Sprague-Dawley rats with 6 weeks pre-pregnancy training were exercised daily from day 1 to day 18 of gestation in water that was 34.6 +/- 0.4 degrees C (Cool Water Swimmers--CWS) or 37.6 +/- 0.1 degrees C (Warm Water Swimmers--WWS), for one hour/day. During this time period another group of pregnant rats was immersed to the neck in warm water (37.6 +/- 0.2 degrees C) (Warm Water Controls--WWC). On day 19 of gestation all animals were sacrificed and fetal development assessed. Maternal exercise in warm water elevated maternal body core temperature by 2.3 +/- 0.1 degrees C above resting values, with an increase in fetal abnormalities compared to the same exercise intensity in cool water. Fifty-eight percent of the abnormal fetuses and 60% of the resorption sites were found in the WWS group. Of the abnormalities determined, 65% were from the WWS group and 45% of these fetuses showed micrencephaly. Results suggest cool water may regulate maternal body temperature during swimming exercise and that swimming in warm water should be avoided during gestation because of potential teratogenic effects.

  8. Responsiveness of fetal rat brain cells to glia maturation factor during neoplastic transformation in cell culture

    DEFF Research Database (Denmark)

    Haugen, A; Laerum, O D; Bock, E

    1981-01-01

    The effect of partially purified extracts from adult pig brains containing a glia maturation protein factor (BE) has been investigated on neural cells during carcinogenesis. Pregnant BD IX-rats were given a single transplacental dose of the carcinogen ethylnitrosourea (EtNU) on the 18th day of ge...... on GFA-content was seen any longer, although some few weakly GFA positive cells could be observed in all permanent cell lines. Fetal rat brain cells therefore seem to become less responsive to this differentiation inducer during neoplastic transformation in cell culture....

  9. Loss of occludin expression and impairment of blood-testis barrier permeability in rats with autoimmune orchitis: effect of interleukin 6 on Sertoli cell tight junctions.

    Science.gov (United States)

    Pérez, Cecilia Valeria; Sobarzo, Cristian Marcelo; Jacobo, Patricia Verónica; Pellizzari, Eliana Herminia; Cigorraga, Selva Beatriz; Denduchis, Berta; Lustig, Livia

    2012-11-01

    Inflammation of the male reproductive tract is accepted as being an important etiological factor of infertility. Experimental autoimmune orchitis (EAO) is characterized by interstitial lymphomononuclear cell infiltration and severe damage of seminiferous tubules with germ cells that undergo apoptosis and sloughing. Because the blood-testis barrier (BTB) is relevant for the protection of haploid germ cells against immune attack, the aim of this study was to analyze BTB permeability and the expression of tight junction proteins (occludin, claudin 11, and tight junction protein 1 [TJP1]) in rats during development of autoimmune orchitis. The role of IL6 as modulator of tight junction dynamics was also evaluated because intratesticular content of this cytokine is increased in EAO rats. Orchitis was induced in Sprague-Dawley adult rats by active immunization with testicular homogenate and adjuvants. Control rats (C) were injected with saline solution and adjuvants. Untreated (N) rats were also studied. Concomitant with early signs of germ cell sloughing, a reduced expression of occludin and delocalization of claudin 11 and TJP1 were detected in the testes of rats with EAO compared to C and N groups. The use of tracers showed increased BTB permeability in EAO rats. Intratesticular injection of IL6 induced focal testicular inflammation, which is associated with damaged seminiferous tubules. Rat Sertoli cells cultured in the presence of IL6 exhibited a redistribution of tight junction proteins and reduced transepithelial electrical resistance. These data indicate the possibility that IL6 might be involved in the downregulation of occludin expression and in the modulation of BTB permeability that occur in rats undergoing autoimmune orchitis.

  10. Wi-Fi (2.45 GHz)- and mobile phone (900 and 1800 MHz)-induced risks on oxidative stress and elements in kidney and testis of rats during pregnancy and the development of offspring.

    Science.gov (United States)

    Özorak, Alper; Nazıroğlu, Mustafa; Çelik, Ömer; Yüksel, Murat; Özçelik, Derviş; Özkaya, Mehmet Okan; Çetin, Hasan; Kahya, Mehmet Cemal; Kose, Seyit Ali

    2013-12-01

    The present study was designed to determine the effects of both Wi-Fi (2.45 GHz)- and mobile phone (900 and 1800 MHz)-induced electromagnetic radiation (EMR) on oxidative stress and trace element levels in the kidney and testis of growing rats from pregnancy to 6 weeks of age. Thirty-two rats and their 96 newborn offspring were equally divided into four different groups, namely, control, 2.45 GHz, 900 MHz, and 1800 MHz groups. The 2.45 GHz, 900 MHz, and 1,800 MHz groups were exposed to EMR for 60 min/day during pregnancy and growth. During the fourth, fifth, and sixth weeks of the experiment, kidney and testis samples were taken from decapitated rats. Results from the fourth week showed that the level of lipid peroxidation in the kidney and testis and the copper, zinc, reduced glutathione (GSH), glutathione peroxidase (GSH-Px), and total antioxidant status (TAS) values in the kidney decreased in the EMR groups, while iron concentrations in the kidney as well as vitamin A and vitamin E concentrations in the testis increased in the EMR groups. Results for fifth-week samples showed that iron, vitamin A, and β-carotene concentrations in the kidney increased in the EMR groups, while the GSH and TAS levels decreased. The sixth week results showed that iron concentrations in the kidney and the extent of lipid peroxidation in the kidney and testis increased in the EMR groups, while copper, TAS, and GSH concentrations decreased. There were no statistically significant differences in kidney chromium, magnesium, and manganese concentrations among the four groups. In conclusion, Wi-Fi- and mobile phone-induced EMR caused oxidative damage by increasing the extent of lipid peroxidation and the iron level, while decreasing total antioxidant status, copper, and GSH values. Wi-Fi- and mobile phone-induced EMR may cause precocious puberty and oxidative kidney and testis injury in growing rats.

  11. Global gene expression analysis in fetal mouse ovaries with and without meiosis and comparison of selected genes with meiosis in the testis

    DEFF Research Database (Denmark)

    Olesen, C.; Nyeng, P.; Kalisz, M.

    2007-01-01

    In order to identify novel genes involved in early meiosis and early ovarian development in the mouse, we used microarray technology to compare transcriptional activity in ovaries without meiotic germ cells at embryonic age 11.5 (E11.5) and E13.5 ovaries with meiosis. Overall, 182 genes were......). These genes had previously only been described in spermatogenesis. The microarray also detected an abundance of vesicle-related genes of which four were upregulated (Syngr2, Stxbp1, Ric-8, SytIX) and one (Myo1c) was downregulated in E13.5 ovaries. Detailed analysis showed that the temporal expression of Syt......IX also coincided with the first meiotic wave in the pubertal testis. This is the first time that SytIX has been reported in non-neuronal tissue. Finally, we examined the expression of one of the uncharacterized genes and found it to be gonad-specific in adulthood. We named this novel transcript "Gonad...

  12. Impact of diisobutyl phthalate and other PPAR agonists on steroidogenesis and plasma insulin and leptin levels in fetal rats

    DEFF Research Database (Denmark)

    Boberg, Julie; Metzdorff, Stine Broeng; Wortziger, Rasmus Henrik Sorgenfryd

    2008-01-01

    of obesity and insulin resistance. These effects could be related to chemical interaction with nuclear receptors such as the peroxisome proliferator activated receptors (PPARs). As several testosterone-reducing drugs are PPAR activators, we aimed to examine whether four PPAR agonists were able to affect....... DiBP and rosiglitazone additionally reduced fetal plasma insulin levels. In mates, DiBP reduced anogenital testosterone production and testicular expression of Insl-3 and genes related to steroidogenesis. distance, PPAR alpha mRNA levels were reduced by DiBP at GD 19 in testis and liver. In females...

  13. Efeito da icterícia obstrutiva na fertilidade, morfologia ovariana e desenvolvimento fetal em ratas Effect of jaundice on fertility, ovarian morphology and fetal development in rats

    Directory of Open Access Journals (Sweden)

    Vivian Resende

    2008-09-01

    Full Text Available Avaliou-se o efeito da icterícia obstrutiva na capacidade reprodutiva, morfologia ovariana e desenvolvimento fetal em ratas, utilizando 53 ratas sexualmente maduras, distribuídas em dois grupos: grupo 1 (n = 28 - ligadura do ducto biliopancreático e grupo 2 (n = 25 - controle. Pode-se concluir que, em presença de hiperbilirrubinemia, a fertilização é viável, a capacidade reprodutiva é muito reduzida, os ciclos estrais tornam-se irregulares, o epitélio vaginal permanece cornificado, os corpos lúteos ovarianos regridem, os corpos lúteos gravídicos não são alterados, aumentando progressivamente durante a prenhez, e o desenvolvimento fetal é gravemente alterado.The effect of jaundice on the reproductive capacity, ovarian morphology and fetal development in rats was assessed in 53 sexually mature rats divided into two groups: group 1 (n = 28 - submitted to ligature of the biliopancreatic duct and group 2 (n = 25 - control - submitted only to sham operation. In jaundice rats fertilization is viable, the reproductive capacity is intensive reduced, the estrus cycles becomes irregular, the corpi lutea is presented in regression, the gravidic lutea is not modified increasing gradually during the pregnancy and the fetal development is seriously impaired.

  14. The expression of inducible nitric oxide synthase (iNOS) in the testis and epididymis of rats with a dihydrotestosterone (DHT) deficiency.

    Science.gov (United States)

    Kolasa, Agnieszka; Marchlewicz, Mariola; Kurzawa, Rafał; Głabowski, Wojciech; Trybek, Grzegorz; Wenda-Rózewicka, Lidia; Wiszniewska, Barbara

    2009-01-01

    In our previous studies, we showed that a finasteride-induced DHT deficiency may cause changes in the morphology of the seminiferous epithelium without any morphological alteration of the epididymis. In this study, we demonstrated the constitutive immunoexpression of inducible nitric oxide synthase (iNOS) in the testis and epididymis of Wistar rats treated with finasteride for 28 days (the duration of two cycles of the seminiferous epithelium) and 56 days (the duration of one spermatogenesis). We noted that a 56-day finasteride treatment mainly caused a decrease in the level of circulating DHT, as well as a statistically insignificant decrease in the level of T. The hormone deficiency also led to a change in the iNOS immnoexpression in the testis and epididymis of the finasteride-treated rats. In vitro, DHT did not modify NO production by the epithelial cells of the caput epididymis even when stimulated with LPS and IFNgamma, but it did give rise to an increase in NO production by the epithelial cells of the cauda epididymis without the stimulation. DHT did not have a statistically significant influence on estradiol production by cultured, LPS- and IFNgamma-stimulated epithelial cells from the caput and cauda epididymis. In conclusion, our data clearly indicates that a finasterideinduced DHT deficiency intensifies the constitutive expression of iNOS in most rat testicular and epididymal cells, so it can be expected that the expression of inducible nitric oxide synthase (iNOS) could be regulated by DHT. On the other hand, the profile of the circulating DHT and T levels strongly suggests that the regulation of constitutive iNOS expression is complex and needs more detailed study.

  15. Reproducible isolation of type II pneumocytes from fetal and adult rat lung using nycodenz density gradients.

    Science.gov (United States)

    Viscardi, R M; Ullsperger, S; Resau, J H

    1992-01-01

    Isolating fresh, relatively pure type II pneumocytes from the lung, particularly of fetal origin, is a difficult process. Separation by buoyant density gradient centrifugation has been used successfully to isolate adult type II cells. There is concern, however, that Percoll, a gradient medium that is commonly used for type II cell isolation, may be toxic to cells. We evaluated a new gradient medium, Nycodenz, that is (1) a true solution, (2) transparent, (3) not metabolized by cells, and (4) nontoxic to cells. Type II pneumocytes were isolated from 19- and 21-day gestation fetal and adult rat lung by elastase digestion and separated on preformed isotonic Nycodenz gradients (2 mL each of 27.6, 20.7, 13.8, and 4.6 (w/v) solutions). Type II pneumocytes were recovered from the density range 1.057-1.061 and identified by binding of FITC-conjugated and gold-complexed Maclura pomifera lectin. Cells derived from 19-day fetal lung contained abundant glycogen and reacted with a monoclonal antibody to the cytokeratins 8 and 18, which are markers of the fetal type II cell. Adult type II cells reacted with antibodies to cytokeratins 8, 18, and 19. Type II cell purity was 79.7 +/- 2.4%, 83.8 +/- 2.8%, and 82.6 +/- 1.8% (means +/- SEM) for 19- and 21-day gestation fetal and adult lung preparations, respectively. Cell viability was greater than 95%. The final cell yield for adult preparations was 17.8 +/- 2.7 x 10(6)/rat (means +/- SEM). To determine if the freshly isolated type II pneumocytes were functionally active, the incorporation of [3H]choline into phosphatidylcholine was measured. The percent saturation of phosphatidylcholine was high for both populations of freshly isolated cells. However, adult type II pneumocytes incorporated [3H]choline into phosphatidylcholine more rapidly than 21-day gestation fetal cells (5.97 x 10(-3) dpm/10(6) cells/h vs. 0.32 x 10(-3) dpm/10(6) cells/h, P less than .005). We have demonstrated that, using the Nycodenz isolation method, it is

  16. Influx of testosterone-binding globulin (TeBG) and TeBG-bound sex steroid hormones into rat testis and prostate

    Energy Technology Data Exchange (ETDEWEB)

    Sakiyama, R.; Pardridge, W.M.; Musto, N.A.

    1988-07-01

    The availability of testosterone and estradiol to Sertoli and prostate cells is dependent upon 1) the permeability properties of the blood-tubular barrier (BTB) of the testis or prostate cell membrane, and 2) sex steroid binding to plasma proteins, such as albumin or testosterone-binding globulin (TeBG). Sex steroid influx into these tissues was studied after in vivo arterial bolus injections of (/sup 3/H)testosterone or (/sup 3/H)estradiol in anesthetized rats. Both testosterone and estradiol were readily cleared across the BTB or prostate cell membrane in the absence of plasma proteins and in the presence of human pregnancy serum, in which testosterone or estradiol are 80-95% distributed to TeBG. The extravascular extraction of (/sup 3/H)TeBG across the BTB or prostate plasma membrane (73 +/- 2% (+/- SE) and 92 +/- 9%, respectively) was significantly greater than extraction of (/sup 3/H)albumin or other plasma space markers and indicative of a rapid first pass clearance of TeBG by Sertoli or prostate cells. In summary, these studies indicate that 1) testosterone and estradiol are readily cleared by Sertoli and prostate cells; 2) albumin- and TeBG-bound sex steroids represent the major circulating pool of bioavailable hormone for testis or prostate; and 3) the TeBG-sex steroid complex may be nearly completely available for influx through the BTB or prostate plasma membrane.

  17. Methoxychlor-induced alteration in the levels of HSP70 and clusterin is accompanied with oxidative stress in adult rat testis.

    Science.gov (United States)

    Vaithinathan, S; Saradha, B; Mathur, P P

    2009-01-01

    Methoxychlor, an organochlorine pesticide, has been reported to induce abnormalities in male reproductive tract. However, the insight into the mechanisms of gonadal toxicity induced by methoxychlor is not well known. We investigated whether treatment with methoxychlor would alter the levels of stress proteins, heat shock proteins (HSP), and clusterin (CLU), and oxidative stress-related parameters in the testis of adult male rats. Animals were exposed to a single dose of methoxychlor (50 mg/kg body weight) orally and were terminated at various time points (0, 3, 6, 12, 24, and 72 h) using anesthetic ether. The levels of HSP70, CLU, and the activities of superoxide dismutase (SOD), catalase, and lipid peroxidation levels were evaluated in a 10% testis homogenate. A sequential reduction in the activities of catalase and SOD with concomitant increase in the levels of thiobarbituric acid reactive substance (TBARS) was observed. These changes elicited by methoxychlor were very significant between 6-12 h of posttreatment. Immunoblot analysis of HSP revealed the expression of HSP72, an inducible form of HSP, at certain time points (3-24 h) following exposure to methoxychlor. Similarly, the levels of secretory CLU (sCLU) were also found to be elevated between 3-24 h of treatment. The present data demonstrate methoxychlor-elicited increase in the levels of inducible HSP72 and sCLU, which could be a part of protective mechanism mounted to reduce cellular oxidative damage.

  18. The effects of Love Canal soil extracts on maternal health and fetal development in rats.

    Science.gov (United States)

    Silkworth, J B; Tumasonis, C; Briggs, R G; Narang, A S; Narang, R S; Rej, R; Stein, V; McMartin, D N; Kaminsky, L S

    1986-10-01

    The effects of a solvent extract of the surface soil of the Love Canal chemical dump site, Niagara Falls, New York, and of a natural extract, or leachate, which is drained from the canal for treatment, on the maternal health and fetal development were determined in rats. The solvent extract, which was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (2, 3,7,8-TCDD) at 170 ppb and numerous other chlorinated organic compounds with the primary identified components being the isomers of benzenehexachloride (BHC), was dissolved in corn oil and administered by gavage to pregnant rats at 0,25,75, or 150 mg crude extract/kg/day on Days 6-15 of gestation. A 67% mortality was observed at the highest dose. The rats were sacrificed on Day 20. Dose-related increases in relative liver weight accompanied by hepatocyte hypertrophy were observed at all dose levels. Fetal birthweight was decreased at 75 and 150 mg extract/kg/day. No major treatment-related soft tissue or skeletal malformations, except for delayed ossification, were observed. Based on literature values for BHC, all of the observed toxicity could be accounted for by the BHC contaminants of the extract. The crude organic phase of the leachate was administered to pregnant rats at 0,10,100, or 250 mg/kg/day as described above. Maternal weight gain decreased at 100 and 250 mg/kg/day, accompanied by 5 and 14% maternal mortality, and 1 and 3 dead fetuses, respectively. Early resorptions and the percentage of dead implants increased whereas fetal birthweights were decreased at 250 mg/kg/day. No major treatment-related soft tissue or skeletal malformations, except for delayed ossification, were observed. The primary components of the complex leachate by mass were tetrachloroethanes; however, 2,3,7,8-TCDD, which was present at 3 ppm, probably accounted for all the observed toxicity.

  19. Effects of Love Canal soil extracts on maternal health and fetal development in rats

    Energy Technology Data Exchange (ETDEWEB)

    Silkworth, J.B.; Tumasonis, C.; Briggs, R.G.; Narang, A.S.; Narang, R.S.; Rej, R.; Stein, V.; McMartin, D.N.; Kaminsky, L.S.

    1986-10-01

    The effects of a solvent extract of the surface soil of the Love Canal chemical dump site, Niagara Falls, New York, and of a natural extract, or leachate, which is drained from the canal for treatment, on the maternal health and fetal development were determined in rats. The solvent extract, which was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (2, 3,7,8-TCDD) at 170 ppb and numerous other chlorinated organic compounds with the primary identified components being the isomers of benzenehexachloride (BHC), was dissolved in corn oil and administered by gavage to pregnant rats at 0,25,75, or 150 mg crude extract/kg/day on Days 6-15 of gestation. A 67% mortality was observed at the highest dose. The rats were sacrificed on Day 20. Dose-related increases in relative liver weight accompanied by hepatocyte hypertrophy were observed at all dose levels. Fetal birthweight was decreased at 75 and 150 mg extract/kg/day. No major treatment-related soft tissue or skeletal malformations, except for delayed ossification, were observed. Based on literature values for BHC, all of the observed toxicity could be accounted for by the BHC contaminants of the extract. The crude organic phase of the leachate was administered to pregnant rats at 0,10,100, or 250 mg/kg/day as described above. Maternal weight gain decreased at 100 and 250 mg/kg/day, accompanied by 5 and 14% maternal mortality, and 1 and 3 dead fetuses, respectively. Early resorptions and the percentage of dead implants increased whereas fetal birthweights were decreased at 250 mg/kg/day. No major treatment-related soft tissue or skeletal malformations, except for delayed ossification, were observed. The primary components of the complex leachate by mass were tetrachloroethanes; however, 2,3,7,8-TCDD, which was present at 3 ppm, probably accounted for all the observed toxicity.

  20. Fetal iron deficiency induces chromatin remodeling at the Bdnf locus in adult rat hippocampus.

    Science.gov (United States)

    Tran, Phu V; Kennedy, Bruce C; Lien, Yu-Chin; Simmons, Rebecca A; Georgieff, Michael K

    2015-02-15

    Fetal and subsequent early postnatal iron deficiency causes persistent impairments in cognitive and affective behaviors despite prompt postnatal iron repletion. The long-term cognitive impacts are accompanied by persistent downregulation of brain-derived neurotrophic factor (BDNF), a factor critical for hippocampal plasticity across the life span. This study determined whether early-life iron deficiency epigenetically modifies the Bdnf locus and whether dietary choline supplementation during late gestation reverses these modifications. DNA methylation and histone modifications were assessed at the Bdnf-IV promoter in the hippocampus of rats [at postnatal day (PND) 65] that were iron-deficient (ID) during the fetal-neonatal period. Iron deficiency was induced in rat pups by providing pregnant and nursing dams an ID diet (4 mg/kg Fe) from gestational day (G) 2 through PND7, after which iron deficiency was treated with an iron-sufficient (IS) diet (200 mg/kg Fe). This paradigm resulted in about 60% hippocampal iron loss on PND15 with complete recovery by PND65. For choline supplementation, pregnant rat dams were given dietary choline (5 g/kg) from G11 through G18. DNA methylation was determined by quantitative sequencing of bisulfite-treated DNA, revealing a small alteration at the Bdnf-IV promoter. Chromatin immunoprecipitation analysis showed increased HDAC1 binding accompanied by reduced binding of RNA polymerase II and USF1 at the Bdnf-IV promoter in formerly ID rats. These changes were correlated with altered histone methylations. Prenatal choline supplementation reverses these epigenetic modifications. Collectively, the findings identify epigenetic modifications as a potential mechanism to explicate the long-term repression of Bdnf following fetal and early postnatal iron deficiency.

  1. Placental transfer and fetal distribution of /sup 3/H-retinoic acid in rats

    Energy Technology Data Exchange (ETDEWEB)

    Shukla, R.R.; Kumar, V.; Banerjee, R.; Misra, U.K.

    1986-01-01

    The placental transfer of /sup 3/H-retinoic acid in vitamin A deprived and vitamin A supplemented pregnant female rats was studied on 20th day of gestation and compared with /sup 3/H-retinyl acetate. Radiolabelled compounds were administered to pregnant mothers orally in groundnut oil six hours before sacrifice. The distribution of radioactivity of the two compounds was studied in maternal intestine, liver and plasma and fetal brain, heart liver lung and placenta. The transfer of /sup 3/H-retinoic acid across placenta was restricted as compared to that of /sup 3/H-retinyl acetate which may explain the reason why retinoic acid does not support fetal growth.

  2. Development of epithelia in the ectopic transplant of the fetal rat epiglottis.

    Science.gov (United States)

    Kulisić, Sandra Marinović; Jurić-Lekić, Gordana; Bulić-Jakus, Floriana; Radujković, Vedran; Parcetić, Ida; Vlahović, Maja; Katusić, Ana; Sincić, Nino; Serman, Ljiljana

    2008-01-01

    Embryonic in situ development is strictly regulated within the specific microenvironment of developing tissues. However, for regenerative medicine purposes (supplementation of damaged tissues/organs), transplantation to ectopic sites has been considered. To investigate developmental potential of fetal epiglottic epithelia at an ectopic site, fetal epiglottis was transplanted under the kidney capsule and its development compared to fetal and adult epiglottis. Seventeen-day-old Fischer rat epiglottides were microsurgically isolated under a dissecting microscope and transplanted under the kidney capsule of adult males. After 14 days, classic histology and immunohistochemical detection of the Proliferating Cell Nuclear Antigen (PCNA) were done in isolated and accordingly fixed transplants. The 17-day-old fetal epiglottis and adult epiglottis were processed in the same way. The 17-day-old fetal epiglottides were covered with immature epithelium expressing PCNA in almost all cells. Adult epiglottis was covered with two types of epithelia (stratified squamous epithelium and ciliated pseudostratified epithelium). In the stratified squamous epithelium PCNA was abundantly expressed in the basal cell layer and absent from more superficial and more differentiated cells. Transplants survived well during the experimental period. On their surface ciliated pseudostratified epithelium could be easily recognized, but squamous epithelium was almost absent. PCNA was expressed in basal cells of the ciliated pseudostratified epithelium and was absent from the more differentiated superficial cells. It seems that at this ectopic site further differentiation of the epiglottic epithelia can proceed but differentiation of squamous epithelium seems not to be favored. It seems that this ectopic site is optimal for further differentiation of the epiglottic epithelium towards ciliated pseudostratified epithelium.

  3. The Effects of Magnesium Sulfate on Fetal Rats of FGR and the Expression of Caspase-3 in the Placenta of Maternal Rat

    Institute of Scientific and Technical Information of China (English)

    GAO Hui; ZOU Li

    2005-01-01

    To investigate the effect of magnesium sulfate on the fetal rats of FGR and the expression of caspase-3 in the placenta of maternal rat; To explore the mechanism of using magnesium sulfate to cure the FGR. Establish model of FGR by a way of passive smoking: giving the maternal rats different agent of magnesium sulfate by subcutaneous injection: low agent group (300 mg/kg),high agent group (600 mg/kg). Concentration of magnesium sulfate was monitored. The expres sion of caspase-3 was measured by RT-PCR and immunohistochemistry technology. Both of the concentrations of magnesium sulfate in high and low agents group are higher than the FGR group (P<0. 01); the weight of the placenta and fetal rat in high agent group are higher than the FGR group (P<0.05 and P<0.01); the expression of mRNA and protein of caspase-3 in the two agent group is higher than the FGR group (P<0.05 respectively); concentration of magnesium sulfate in the maternal rat blood correlate to the weight of fetal rat (r=0. 899, P=0. 038) and the expression of caspase-3 in the placenta of maternal rat (r= 0.747, P 0.033; r=-0. 915, P=0.001).The research suggests that the weight of fetal rat could be increased by treatment of magnesium sulfate. Because it would imfrmove the placental function by depressing the expression of caspase-3.

  4. Toxicity of bryostatin-1 on the embryo-fetal development of Sprague-Dawley rats.

    Science.gov (United States)

    Jiangbo, Zhu; Xuying, Wan; Yuping, Zhu; Xili, Ma; Yiwen, Zheng; Tianbao, Zhang

    2010-06-01

    Bryostatin-1, a highly oxygenated marine macrolide with a unique polyacetate backbone isolated from the marine animal Bugula neritina (Linnaeus), is now being developed as an anti-cancer drug for treating malignancy. In the present study, developmental toxicity of bryostatin-1 was evaluated in Sprague-Dawley rats. Bryostatin-1 was intravenously administered to rats on gestation days 6-15 at 4.0, 8.0, and 16.0 microg/kg on a daily basis. Then the reproductive parameters were determined in animals, and fetuses were examined for external, visceral, and skeletal malformations. The total weight gains were significantly different in animals between the control group and 8.0 and 16.0 microg/kg bryostatin-1 groups during and after treatment. The resorption and death fetus rates were significantly different between the bryostatin-1 group (16 microg/kg) and the control group. The fetal weight and fetal crown-rump length in the bryostatin-1 groups were significantly lower than that in the control group. Our results indicated that maternal toxicity occurred when the dose of bryostatin-1 was at 8.0 microg/kg, embryotoxicity at 16.0 microg/kg, and fetotoxicity at 4.0 microg/kg; but bryostatin-1 showed no teratogenic effect in rats. In light of our findings, bryostatin-1 should be used with caution in pregnant women with cancer, if they would like to continue the pregnancy.

  5. Repercussions of mild diabetes on pregnancy in Wistar rats and on the fetal development

    Directory of Open Access Journals (Sweden)

    Saito Felipe H

    2010-04-01

    Full Text Available Abstract Background Experimental models are necessary to elucidate diabetes pathophysiological mechanisms not yet understood in humans. Objective: To evaluate the repercussions of the mild diabetes, considering two methodologies, on the pregnancy of Wistar rats and on the development of their offspring. Methods In the 1st induction, female offspring were distributed into two experimental groups: Group streptozotocin (STZ, n = 67: received the β-cytotoxic agent (100 mg STZ/kg body weight - sc on the 1st day of the life; and Non-diabetic Group (ND, n = 14: received the vehicle in a similar time period. In the adult life, the animals were mated. After a positive diagnosis of pregnancy (0, female rats from group STZ presenting with lower glycemia than 120 mg/dL received more 20 mg STZ/kg (ip at day 7 of pregnancy (2nd induction. The female rats with glycemia higher than 120 mg/dL were discarded because they reproduced results already found in the literature. In the mornings of days 0, 7, 14 and 21 of the pregnancy glycemia was determined. At day 21 of pregnancy (at term, the female rats were anesthetized and killed for maternal reproductive performance and fetal development analysis. The data were analyzed using Student-Newman-Keuls, Chi-square and Zero-inflated Poisson (ZIP Tests (p Results STZ rats presented increased rates of pre (STZ = 22.0%; ND = 5.1% and post-implantation losses (STZ = 26.1%; ND = 5.7%, reduced rates of fetuses with appropriate weight for gestational age (STZ = 66%; ND = 93% and reduced degree of development (ossification sites. Conclusion Mild diabetes led a negative impact on maternal reproductive performance and caused intrauterine growth restriction and impaired fetal development.

  6. Effects of strenuous maternal exercise on fetal organ weights and skeletal muscle development in rats.

    Science.gov (United States)

    Mottola, M F; Bagnall, K M; Belcastro, A N

    1989-02-01

    The purpose of the present study was to observe the effects of strenuous maternal aerobic exercise throughout gestation on fetal outcome in the rat. The strenuous exercise intensity consisted of a treadmill speed of 30 m.min-1 on a 10 degrees incline, for 120 min.day-1, 5 days.week-1. The rats were conditioned to run on a motor-driven treadmill by following a progressive two-week exercise program, so that by the end of the two weeks the rats were capable of running comfortably at this strenuous intensity in the non-pregnant state. Following the two-week running programme, the rats were paired by weight and randomly assigned to either a pregnant group that continued the running program throughout gestation (pregnant runner), or a pregnant group that did not continue the running program throughout pregnancy (pregnant control). At birth the neonates born to the pregnant running group did not differ in average neonatal body weight values, number per litter or total litter weight values when compared to controls, nor were superficial gross abnormalities observed in neonates born to the pregnant control or pregnant running groups. The strenuous maternal exercise intensity did not alter neonatal organ weight values (brain, heart, liver, lung, kidney), nor neonatal skeletal muscle (gastrocnemius, sternomastoid, diaphragm) when compared to control values. It is suggested that maternal exercise of this intensity throughout gestation does not affect fetal outcome in the rat, and may be due to the animals accustomization to the strenuous exercise protocol prior to pregnancy.

  7. Thyroxine inner ring monodeiodinating activity in fetal tissues of the rat

    Energy Technology Data Exchange (ETDEWEB)

    Huang, T.S.; Chopra, I.J.; Boado, R.; Soloman, D.H.; Chua Teco, G.N.

    1988-02-01

    We studied thyroxine (T4) inner ring monodeiodinating activity (5-MA) in various tissues of fetal, maternal, and adult male rats. Tissue homogenates were incubated with 0.26 microM T4 in 0.1 M phosphate buffer (pH 7.4) containing 10 mM EDTA and 400 mM dithiothreitol (final volume 0.7 ml) for 10 min at 37 degrees C; the 3,3',5'-triiodothyronine (rT3) generated was measured by radioimmunoassay of ethanol extracts of incubation mixture and the result was corrected for rT3 degradation during incubation. Compared to maternal tissues, T4 to rT3 5-MA in the 14-day-old fetus was increased about 70 times in skeletal muscle (mean +/- SEM, velocity, 5.4 +/- 0.9 versus 0.08 +/- 0.01, pmol rT3/h/mg protein); approximately 8 times in intestine (0.72 +/- 0.17 versus 0.09 +/- 0.03);and approximately 4 times in cerebral cortex (19 +/- 0.5 versus 4.5 +/- 0.9), while it was similar in skin (3.2 +/- 0.48 versus 2.6 +/- 0.52). Hepatic T4 5-MA approximated 1.1 +/- 0.63 in the 14-day-old fetus; it could not be measured reliably in maternal or 19-day fetal tissue because of extensive (greater than 90%) degradation of rT3 during incubation. Relative to mother, T4 5-MA in 19-day fetal tissues was increased approximately 30-fold intestine, approximately 20-fold in skeletal muscle, and approximately 6-fold in cerebral cortex while it was similar in skin. The T4 5-MA in maternal rat tissues did not differ significantly from corresponding values in adult male rat, except skin, where it was lower in the mother rat (2.6 +/- 0.52 versus 4.6 +/- 0.61, p less than 0.05). In summary, relative to adult tissues T4 5-MA is exceedingly active in several fetal tissues, most notably in skeletal muscle followed by intestine and cerebral cortex.

  8. Caffeine-induced activated glucocorticoid metabolism in the hippocampus causes hypothalamic-pituitary-adrenal axis inhibition in fetal rats.

    Science.gov (United States)

    Xu, Dan; Zhang, Benjian; Liang, Gai; Ping, Jie; Kou, Hao; Li, Xiaojun; Xiong, Jie; Hu, Dongcai; Chen, Liaobin; Magdalou, Jacques; Wang, Hui

    2012-01-01

    Epidemiological investigations have shown that fetuses with intrauterine growth retardation (IUGR) are susceptible to adult metabolic syndrome. Clinical investigations and experiments have demonstrated that caffeine is a definite inducer of IUGR, as children who ingest caffeine-containing food or drinks are highly susceptible to adult obesity and hypertension. Our goals for this study were to investigate the effect of prenatal caffeine ingestion on the functional development of the fetal hippocampus and the hypothalamic-pituitary-adrenal (HPA) axis and to clarify an intrauterine HPA axis-associated neuroendocrine alteration induced by caffeine. Pregnant Wistar rats were intragastrically administered 20, 60, and 180 mg/kg · d caffeine from gestational days 11-20. The results show that prenatal caffeine ingestion significantly decreased the expression of fetal hypothalamus corticotrophin-releasing hormone. The fetal adrenal cortex changed into slight and the expression of fetal adrenal steroid acute regulatory protein (StAR) and cholesterol side-chain cleavage enzyme (P450scc), as well as the level of fetal adrenal endogenous corticosterone (CORT), were all significantly decreased after caffeine treatment. Moreover, caffeine ingestion significantly increased the levels of maternal and fetal blood CORT and decreased the expression of placental 11β-hydroxysteroid dehydrogenase-2 (11β-HSD-2). Additionally, both in vivo and in vitro studies show that caffeine can downregulate the expression of fetal hippocampal 11β-HSD-2, promote the expression of 11β-hydroxysteroid dehydrogenase 1 and glucocorticoid receptor (GR), and enhance DNA methylation within the hippocampal 11β-HSD-2 promoter. These results suggest that prenatal caffeine ingestion inhibits the development of the fetal HPA axis, which may be associated with the fetal overexposure to maternal glucocorticoid and activated glucocorticoid metabolism in the fetal hippocampus. These results will be beneficial in

  9. Effect of telmisartan and insulin on endoplasmic reticulum stress and the expression of Sirt1 in testis of type 1 diabetic rats

    Directory of Open Access Journals (Sweden)

    Yan HUANG

    2016-10-01

    Full Text Available Objective  To observe the regulation effect of insulin and telmisartan on the endoplasmic reticulum stress (ERS and the expression of silent information regulator 1 (Sirt1 in the testes of type 1 diabetic rats, and explore the protective effect and mechanism of insulin and telmisartan on the testicular tissue of diabetic rats. Methods  Male Sprague-Dawley (SD rats were randomly divided into normal control group (group A, n=8, diabetic control group (group B, n=8, diabetic treated with insulin group (group C, n=8 and diabetic treated with telmisartan group (group D, n=8. Diabetic rats were induced by a single intraperitoneal injection of streptozotocin. Rats in group C were subcutaneously injected with protamine-zinc insulin once a day, and in group D were given telmisartan once a day by gavage. Only at the end of the eighth week can specimens be taken. And then some tasks were performed such as calculating the testicular weight and testis index, accounting the quantity and activity rate of sperm, detecting the testosterone levels and mRNA expression levels of CCAAT/enhancer binding protein homologous protein (CHOP, glucose regulated protein (GRP-78, cysteine aspartic acid specific protease 12 (caspase-12 and Sirt1. Results  The levels of testosterone, testes weight, sperm counts and motility significantly decreased in group B than in group A (P0.05. The mRNA expression levels of testicular CHOP, GRP-78 and caspase-12 significantly decreased (P0.05. Conclusion  Insulin and telmisartan may play a protective role on testicular tissues by down-regulating the expression of endoplasmic reticulum stress and up-regulating the expression of Sirt1. DOI: 10.11855/j.issn.0577-7402.2016.10.03

  10. Effect of fetal growth on maternal protein metabolism in postabsorptive rat

    Energy Technology Data Exchange (ETDEWEB)

    Ling, P.R.; Bistrian, B.R.; Blackburn, G.L.; Istfan, N.

    1987-03-01

    Rates of protein synthesis were measured in whole fetuses and maternal tissues at 17 and 20 days of gestation in postabsorptive rats using continuous infusion of L-(1-/sup 14/C)leucine. Fetal protein degradation rates were derived from the fractional rates of synthesis and growth. Whole-body (plasma) leucine kinetics in the mother showed a significant reduction of the fraction of plasma leucine oxidized in the mothers bearing older fetuses, a slight increase in the plasma flux, with total leucine oxidation and incorporation into protein remaining similar at the two gestational ages. Estimates of fractional protein synthesis in maternal tissues revealed an increase in placental and hepatic rates at 20 days of gestation, whereas the fractional synthetic rate in muscle remained unchanged. A model for estimation of the redistribution of leucine between plasma and tissues is described in detail. This model revealed a more efficient utilization of leucine in fetal protein synthesis in comparison with other maternal tissues, a greater dependency of the fetus on plasma supply of leucine, and a significant increase (2-fold) in the release of leucine from maternal muscle as the fetal requirements increased proportionately with its size. The latter conclusion, supported by nitrogen analysis and the ratio of bound-to-free leucine in maternal tissues, confirms the importance of maternal stores in maintaining the homeostasis of essential amino acids during late pregnancy.

  11. Distribution of Interstitial Cells of Cajal in the Esophagus of Fetal Rats with Esophageal Atresia

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    Caner Isbir

    2016-04-01

    Full Text Available Aim: Scarcity of the interstitial cells of Cajal (ICC is related to motility disorders. In the study, we aimed to evaluate the number and density of ICCs in the fetal rat esophagus in the adriamycin - esophageal atresia (EA model. Material and Method: Rat fetuses were divided into three groups as a control, adriamycin group without EA and adriamycin group with EA. Four doses of adriamycin, 2 mg/kg each, were injected intraperitoneally to the adriamycin group rats between on 6 and 9 days of gestation. The presence of ICCs in the esophagus of the rat fetuses was determined by using an immunohistochemistry technique (c-kit, CD117. The average numbers of ICCs were calculated with microscopic evaluation by using a visual scoring system (range1 to 3. Results: Seven fetuses were included in each group. The ICCs score 3 distributions of fetuses were 5 (72% fetuses in the control group, 3 (43% fetuses in the adriamycin group without EA, 1 (14% fetus in the adriamycin group with EA. It have been found that there was a marked reduction of ICCs distribution in the adriamycin group with EA compared to control group (p 0.05. Discussion: ICCs density was significantly decreased in the rat fetuses with EA compared to the fetuses without EA. These findings support the idea that ICCs density may be congenitally abnormal in EA. This may be led to dismotility seen in the operated esophagus due to EA.

  12. Toxic effects of maternal zearalenone exposure on uterine capacity and fetal development in gestation rats.

    Science.gov (United States)

    Zhang, Yuanyuan; Jia, Zhiqiang; Yin, Shutong; Shan, Anshan; Gao, Rui; Qu, Zhe; Liu, Min; Nie, Shaoping

    2014-06-01

    The objectives of this study were to determine the effects of high-dose and early gestational exposure to zearalenone (ZEN) in female Sprague-Dawley (SD) rats, to correlate the maternal uterus with the fetus, and to explore the development and malformation of fetuses. Pregnant female SD rats were fed diets containing 0.3, 48.5, 97.6, or 146.0 mg/kg ZEN on gestational days (GDs) 0 through 7. All the females survived until GD 20, at which point a cesarean section was performed to harvest the organs, blood, and fetuses. The results indicated that exposure to ZEN during early gestation can impact the maternal reproductive capability. Delayed fetal development was directly linked to maternal toxicity. The toxic effects of ZEN caused early deaths more frequently than late deaths, and the deleterious effects lasted through the end of pregnancy.

  13. Diabetic rats exercised prior to and during pregnancy: maternal reproductive outcome, biochemical profile, and frequency of fetal anomalies.

    Science.gov (United States)

    Damasceno, Débora Cristina; Silva, Hellen Pontes; Vaz, Geizi Fátima; Vasques-Silva, Francine Aparecida; Calderon, Iracema Mattos Paranhos; Rudge, Marilza Vieira Cunha; Campos, Kleber Eduardo; Volpato, Gustavo Tadeu

    2013-07-01

    The aim of this study was to evaluate the effects of exercise prior to or during pregnancy on maternal reproductive outcome, biochemical profile, and on fetal anomaly frequency in a rat pregnancy model utilizing chemically induced diabetes. Wistar rats (minimum n = 11 animals/group) were randomly assigned the following groups: group 1 (G1), sedentary, nondiabetic; G2, nondiabetic, exercised during pregnancy; G3, nondiabetic, exercised prior to and during pregnancy; G4, sedentary, diabetic; G5, diabetic, exercised during pregnancy; and G6, diabetic, exercised prior to and during pregnancy. A swimming program was utilized for moderate exercise. On day 21 of pregnancy, all rats were anesthetized to obtain blood for biochemical measurements. The gravid uterus was weighed with its contents, and the fetuses were analyzed. The nondiabetic rats exercised prior to pregnancy presented a reduced maternal weight gain. Besides, G2 and G3 groups showed decreased fetal weights at term pregnancy, indicating slight intrauterine growth restriction (IUGR). In the diabetic dams, the swimming program did not have antihyperglycemic effects. The exercise applied only during pregnancy caused severe IUGR, as confirmed by reduced fetal weight mean, fetal weight classification, and ossification sites. Nevertheless, exercise was not a teratogenic factor and improved the rats' lipid profiles, demonstrating that the exercise presented possible benefits, but there are also risks prior and during pregnancy, especially in diabetic pregnant women.

  14. Exposure to perfluorooctane sulfonate in utero reduces testosterone production in rat fetal Leydig cells.

    Directory of Open Access Journals (Sweden)

    Binghai Zhao

    Full Text Available BACKGROUND: Perfluorooctane sulfonate (PFOS is a synthetic material that has been widely used in industrial applications for decades. Exposure to PFOS has been associated with decreased adult testosterone level, and Leydig cell impairment during the time of adulthood. However, little is known about PFOS effects in utero on fetal Leydig cells (FLC. METHODS AND RESULTS: The present study investigated effects of PFOS on FLC function. Pregnant Sprague Dawley female rats received vehicle (0.05% Tween20 or PFOS (5, 20 mg/kg by oral gavage from gestational day (GD 11-19. At GD20, testosterone (T production, FLC numbers and ultrastructure, testicular gene and protein expression levels were examined. The results indicate that exposures to PFOS have affected FLC function as evidenced by decreased T production, impaired FLC, reduced FLC number, and decreased steroidogenic capacity and cholesterol level in utero. CONCLUSION: The present study shows that PFOS is an endocrine disruptor of male reproductive system as it causes reduction of T production and impairment of rat fetal Leydig cells.

  15. Evaluation of embryonic alcoholism from auditory event-related potential in fetal rats

    Institute of Scientific and Technical Information of China (English)

    梁勇; 王正敏; 屈卫东

    2004-01-01

    @@ Auditory event-related potential (AERP) is a kind of electroencephalography that measures the responses of perception, memory and judgement to special acoustic stimulation in the auditory cortex. AERP can be recorded with not only active but also passive mode. The active and passive recording modes of AERP have been shown a possible application in animals.1,2 Alcohol is a substance that can markedly affect the conscious reaction of human. Recently, AERP has been applied to study the effects of alcohol on the auditory centers of the brain. Some reports have shown dose-dependent differences in latency, amplitude, responsibility and waveform of AERP between persons who have and have not take in alcohol.3,4 The epidemiological investigations show that the central nervous function of the offspring of alcohol users might be also affected.5,6 Because the clinic research is limited by certain factors, several animal models have been applied to examine the influences of alcohol on consciousness with AERP. In the present study, young rats were exposed to alcohol during fetal development and AERP as indicator was recorded to monitor the central auditory function, and its mechanisms and characteristics of effects of the fetal alcoholism on auditory center function in rats were analyzed and discussed.

  16. Morpho-functional characteristics of rat fetal thyroid gland are affected by prenatal dexamethasone exposure.

    Science.gov (United States)

    Manojlović-Stojanoski, Milica N; Filipović, Branko R; Nestorović, Nataša M; Šošić-Jurjević, Branka T; Ristić, Nataša M; Trifunović, Svetlana L; Milošević, Verica Lj

    2014-06-01

    Thyroid hormones (TH) and glucocorticoids strongly contribute to the maturation of fetal tissues in the preparation for extrauterine life. Influence of maternal dexamethasone (Dx) administration on thyroid glands morpho-functional characteristics of near term rat fetuses was investigated applying unbiased stereology. On the 16th day of pregnancy dams received 1.0mg/Dx/kg/b.w., followed by 0.5mg/Dx/kg/b.w. on the 17th and 18th days of gestation. The control females received the same volume of saline. The volume of fetal thyroid was estimated using Cavalieri's principle; the physical/fractionator design was applied for the determination of absolute number of follicular cells in mitosis and immunohistochemically labeled C cells; C cell volume was measured using the planar rotator. The functional activity of thyroid tissue was provided from thyroglobulin (Tg) and thyroperoxidase (TPO) immunohistochemical staining. Applying these design-based modern stereological methods it was shown that Dx treatment of gravid females led to a significant decrease of fetal thyroid gland volume in 19- and 21-day-old fetuses, due to decreased proliferation of follicular cells. The Tg and TPO immunohistochemistry demonstrated that intensive TH production starts and continues during the examined period in control and Dx-exposed fetuses. Under the influence of Dx the absolute number of C cells was lower in both groups of near term fetuses, although unchanged relation between the two populations of endocrine cells, follicular and C cells suggesting that structural relationships within the gland are preserved. In conclusion maternal glucocorticoid administration at the thyroid gland level exerts growth-inhibitory and maturational promoting effects in near term rat fetuses.

  17. Effect of boric acid on oxidative stress in rats with fetal alcohol syndrome.

    Science.gov (United States)

    Sogut, Ibrahim; Oglakci, Aysegul; Kartkaya, Kazim; Ol, Kevser Kusat; Sogut, Melis Savasan; Kanbak, Gungor; Inal, Mine Erden

    2015-03-01

    To the best of our knowledge, this is the first study concerning the effect of boric acid (BA) administration on fetal alcohol syndrome (FAS). In this study, the aim was to investigate prenatal alcohol-induced oxidative stress on the cerebral cortex of newborn rat pups and assess the protective and beneficial effects of BA supplementation on rats with FAS. Pregnant rats were divided into three groups, namely the control, alcohol and alcohol + boric acid groups. As markers of alcohol-induced oxidative stress in the cerebral cortex of the newborn pups, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels were measured. Although the MDA levels in the alcohol group were significantly increased compared with those in the control group (Pboric acid group was shown to be significantly decreased compared with that in the alcohol group (Pboric acid group was significantly higher than that in the alcohol group (P<0.05). The GPx activity in the alcohol group was decreased compared with that in the control group (P<0.05). These results demonstrate that alcohol is capable of triggering damage to membranes of the cerebral cortex of rat pups and BA could be influential in antioxidant mechanisms against oxidative stress resulting from prenatal alcohol exposure.

  18. Evaluation of histological changes after tracheal occlusion at different gestational ages in a fetal rat model

    Directory of Open Access Journals (Sweden)

    Rodrigo Melo Gallindo

    2013-01-01

    Full Text Available OBJECTIVES: To evaluate the histological changes of tracheal cartilage and epithelium caused by tracheal occlusion at different gestational ages in a fetal rat model. METHODS: Rat fetuses were divided into two groups: a External control, composed of non-operated rats, and b Interventional group, composed of rats operated upon on gestational day 18.5 (term = 22 days, divided into triads: 1 Tracheal occlusion, 2 Internal control and 3 Sham (manipulated but not operated. Morphological data for body weight, total lung weight and total lung weight/body weight ratio were collected and measured on gestational days 19.5, 20.5 and 21.5. Tracheal samples were histologically processed, and epithelial, chondral and total tracheal thicknesses were measured on each gestational day. RESULTS: The tracheal occlusion group exhibited an increase in total lung weight/body weight ratio (p<0.001. Histologically, this group had a thicker epithelial thickness (p<0.05 and thinner chondral (p<0.05 and total tracheal thicknesses (p<0.001. These differences were more prominent on gestational days 20.5 and 21.5. CONCLUSION: Tracheal occlusion changed tracheal morphology, increased epithelial thickness and considerably decreased total tracheal thickness. These changes in the tracheal wall could explain the development of tracheomegaly, recently reported in some human fetuses subjected to tracheal occlusion.

  19. In utero glucocorticoid exposure reduced fetal skeletal muscle mass in rats independent of effects on maternal nutrition

    Science.gov (United States)

    Maternal stress and undernutrition can occur together and expose the fetus to high glucocorticoid (GLC) levels during this vulnerable period. To determine the consequences of GLC exposure on fetal skeletal muscle independently of maternal food intake, groups of timed-pregnant Sprague-Dawley rats (n ...

  20. The Effects of Anethum graveolens L. Seeds on the Male Reproductive Functions and CREM Gene Expression in the Testis of Rat

    Directory of Open Access Journals (Sweden)

    Parisa Shojaee

    2014-03-01

    Full Text Available It is undeniable that the increasing of the population in the developing countries is an anxiety, therefore finding safe and effective contraceptive materials can be very useful. The aim of this study was to investigate the effects of Anethum graveolens L. on the reproductive system of male rat and CREM gene expression in testis of rat. Animals were randomly divided into two groups of control (treated with normal salin for the period of 56 days, n = 8 and experimental (treated with 150 mg/kg/day of Anethum graveolens extract for 56 days, n = 8. RT-PCR and histological studies, hormonal assay and sperm analysis were carried out for evaluating of extract on reproductive function of rat. Results indicated no significant differences between body weights of control and experimental groups. Sperm counts and motility were reduced however there was an increase sperm abnormality by applying of extract. Indeed existence of disorganized germinal epitheliums, degeneration, necrotic cells in some of seminiferous tubules and lower concentration of sperms in the center of seminiferous tubules of experimental group was noticeable. Results also showed reduction in the diameter of seminiferous tubules of experimental groups comparing with control groups. Administration of extract caused a significant decline in the plasma level of testosterone. Our RT-PCR data revealed that CREM mRNA levels decreased significantly in testes from the experimental group in compared to control group. In conclusionAnethum graveolens has strong anti-spermatogenic activity by decreasing sperm parameters. This study strongly proposes that this plant can be a good candidate for manufacturing antifertility drugs.

  1. Therapeutic effect of hyperbaric and normobaric oxygen therapy on experimental fetal growth restriction in rats

    Directory of Open Access Journals (Sweden)

    Ting WAN

    2011-10-01

    Full Text Available Objective To explore the therapeutic effect of hyperbaric and normobaric oxygen on experimental fetal growth restriction(FGR in rats.Methods Forty pregnant Sprague-Dawley rats were divided into five groups(8 each: control group(group N,did nothing to rats,sham operation group(group M,rats were only anesthetized on day 12 of gestation and did nothing else except that,FGR model group(group F,rats accepted partial ligation of both uterine arteries and veins on day 12 of gestation and no therapy after that,hyperbaric oxygen therapy group(group A,rats accepted hyperbaric oxygen treatment after the operation,normobaric hyperoxia therapy group(group B,rats accepted normobaric oxygen treatment after the operation.On day 21 of gestation,the fetuses and placentas in all groups were surgically taken out and weighted,and the incidence of FGR and mortality in the fetus,and pathological changes of placentas were analyzed.Results Newborn’s weight in group F,N,M,A and B respectively were 3.26±0.49g,4.57±0.37g,4.46±0.36g,4.11±0.37g and 4.08±0.32g,and the placenta weight were 0.40±0.05g,0.54±0.07g,0.53±0.08g,0.47±0.05g and 0.46±0.05g.Newborn’s weight and placenta in group F were significantly lower than that in group N and M(P 0.05.FGR rates in group N,M,F,A and B respectively were 1.33%,2.94%,83.10%,13.63% and 13.89%,and mortality rates were 1.33%,1.47%,11.27%,6.06% and 6.94%.The incidence of FGR and the mortality in group F were significantly higher than that in group N(P < 0.01,and in group A and B were significantly lower than that in group N(P < 0.01.Blood stasis and villous ischemia were found in placenta of FGR model rats.Placental microcirculation was significantly improved in treatment groups.Conclusion Both hyperbaric oxygen and normobaric oxygen have a similar and good therapeutic effect on experimental FGR in rats.

  2. THE EFFECT OF THE MULTIGLYCOSIDES OF TRIPTERYGIUM WILFORDII ON THE HYPOTHALAMOPITUITARY-TESTIS AXIS OF MALE RATS

    Institute of Scientific and Technical Information of China (English)

    TONGJian-Sun; QINJin-Xi; LIUXi-Guang; SUNYun-Tian; D.M.deKretser

    1989-01-01

    The multiglycosides of Tripterygium wilfordii Hook. f. (GTW) is a Chinese herb medicine used traditionally for the treatment of rheumatoid arthritis, chronic nephritis and some skin diseases. It has been recently shown to cause infertility in men, male rats and

  3. Quantitative analysis of motor neurons of the levator ani muscle in fetal rats with spina bifida occulta.

    Science.gov (United States)

    Li, Yong; Hou, Xiang-Yu; Yuan, Zheng-Wei; Wang, Wei-Lin

    2009-12-01

    With the combination of microsurgery and microinjection techniques, we investigated the development of motor neurons in the spinal cord of fetal rats with spina bifida occulta by injecting the retrograde trace FG into the levator ani muscle. The fetal rats were divided into 3 groups. On the day 9 of gestation, 6 mature Wistar rats (weighing 250-300 g) in the control group (group 1) were subcutaneously injected with 0.5 mL of normal saline at their hind limbs at 9:00 am and 4:00 pm. At these 2 time points, 15 rats in the treatment group (group 2 and group 3) were subcutaneously injected with 20% sodium valproate solution (400 mg/kg of body weight) at their hind limbs, too. On the day 20 of gestation, pregnant rats were anesthetized with 10% chloral hydrate (300 mg/kg of body weight) intraperitoneally, and then fetal microsurgery and microinjection were performed to expose the levator ani muscle, whereas 5% FG was administered with microinjector. Twenty-four hours later, transcardial perfusion of 4% paraformaldehyde in phosphate-buffered saline (PBS) was given to the operated fetus. After the spine sample was stained with Alcian blue GX, the image of stained spine was measured using a computer system for the distance of the 2 cartilaginous ends of the vertebra arch. Then, the lumbosacral spinal cord was cryopreserved in 20% sucrose in PBS for a later serial transverse cryosection after 24 hours. The FG-labeled motor neurons were visualized with a wide-band ultraviolet-fluorescent filter, and the number of the FG-labeled motor neurons was recorded. Nine fetal rats survived in group 1. Eighteen fetal rats survived in the treatment group, including 7 (with no malformation) of 18 fetuses in group 2 and 11 fetuses with spina bifida occulta in group 3. The FG-labeled motor neurons in the ventral horn of normal spinal cord clustered at the dorsolateral and dorsomedial corner of the ventral horn. The FG-labeled motor neurons in the ventral horn of deformed spinal cord were

  4. Characterization of insulin-like growth factor I produced by fetal rat pancreatic islets

    Energy Technology Data Exchange (ETDEWEB)

    Scharfmann, R.; Corvol, M.; Czernichow, P. (Institut National de la Sante et de la Recherche Medicale (Unit 30), Paris (France))

    1989-06-01

    Pancreatic islets were prepared from 22-day-old rat fetuses. After 5 days of culture in dishes allowing cell attachment, neoformed islets were kept free floating in RPMI-1640 medium (16.5 mM glucose, 1% fetal calf serum). The islets were then pulsed with ({sup 3}H)leucine and ({sup 35}S)methionine for 24 h. The conditioned medium was acidified with acetic acid (final pH 2.7), desalted, concentrated, and gel filtered on Bio-Gel P100 in acid conditions. The radioactive material that comigrated with immunoreactive insulinlike growth factor I (IGF-I) produced by the islets was pooled, concentrated, and further characterized by reverse-phase high-performance liquid chromatography on a C18 Bondapak column with a linear gradient of acetonitrile (20-80%). The radioactive material that eluted as pure IGF-I (40% acetonitrile) was further studied by chromatofocusing on a Pharmacia PBE 94 column. A sharp radioactive peak containing ({sup 3}H)leucine and ({sup 35}S)methionine was eluted at pH 8.55. This material was immunoprecipitated with an antiserum to IGF-I. This study demonstrated that fetal islet cells synthesize molecules that are, by several criteria, equivalent to native IGF-I.

  5. Lack of action of exogenously administered T3 on the fetal rat brain despite expression of the monocarboxylate transporter 8.

    Science.gov (United States)

    Grijota-Martínez, Carmen; Díez, Diego; Morreale de Escobar, Gabriella; Bernal, Juan; Morte, Beatriz

    2011-04-01

    Mutations of the monocarboxylate transporter 8 gene (MCT8, SLC16A2) cause the Allan-Herndon-Dudley syndrome, an X-linked syndrome of severe intellectual deficit and neurological impairment. Mct8 transports thyroid hormones (T4 and T3), and the Allan-Herndon-Dudley syndrome is likely caused by lack of T3 transport to neurons during critical periods of fetal brain development. To evaluate the role of Mct8 in thyroid hormone action in the fetal brain we administered T4 or T3 to thyroidectomized pregnant dams treated with methyl-mercapto-imidazol to produce maternal and fetal hypothyroidism. Gene expression was then measured in the fetal cerebral cortex. T4 increased Camk4, Sema3c, and Slc7a3 expression, but T3 was without effect. To investigate the cause for the lack of T3 action we analyzed the expression of organic anion transport polypeptide (Oatp14, Slco1c1), a T4 transporter, and Mct8 (Slc16a2), a T4 and T3 transporter, by confocal microscopy. Both proteins were present in the brain capillaries forming the blood-brain barrier and in the epithelial cells of the choroid plexus forming the blood-cerebrospinal fluid barrier. It is concluded that T4 from the maternal compartment influences gene expression in the fetal cerebral cortex, possibly after transport via organic anion transporter polypeptide and/or Mct8, and conversion to T3 in the astrocytes. On the other hand, T3 does not reach the target neurons despite the presence of Mct8. The data indicate that T4, through local deiodination, provides most T3 in the fetal rat brain. The role of Mct8 as a T3 transporter in the fetal rat brain is therefore uncertain.

  6. Isolation and differentiation of neural stem/progenitor cells from fetal rat dorsal root ganglia

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    To find a promising alternative to neurons or schwann cells (SCs) for peripheral nerve repair applications,this study sought to isolate stem cells from fetal rat dorsal root ganglion (DRG) explants.Molecular expression analysis confirmed neural stem cell characteristics of DRG-derived neurospheres in terms of expressing neural stem cell-specific genes and a set of well-defined genes related to stem cell niches and glial fate decision.Under the influence of neurotrophic factors,bFGF and NGF,the neurospheres gave rise to neurofilament-expressing neurons and S100-expressing Schwann cell-like cells by different pathways.This study suggests that a subpopulation of stem cells that reside in DRGs is the progenitor of neurons and glia,which could directly induce the differentiation toward neurons,or SCs.

  7. Effect of restricted food supply to pregnant rats inhaling carbon monoxide on fetal weight, compared with cigarette smoke exposure

    Energy Technology Data Exchange (ETDEWEB)

    Tachi, N.; Aoyama, M.

    1986-12-01

    Although many studies have shown that cigarette smoking during gestation retarded the intrauterine fetal growth, resulting in the decreased birth weight in babies born to smoking mothers, neither causal substance nor mechanism of action to disturb fetal growth has been firmly established yet. Based on the human and animal studies, researchers have implied that fetal hypoxia induced by carbon monoxide (CO) in the cigarette smoke to be responsible for the event. A shortage in energy intake in smoking mothers also has been suspected to cause the retardation in fetal development. In the previous results (Tachi and Aoyama 1983), the weight increment in CO exposed animals was greater than that in the smoke exposed group. The phenomenon seemed to indicate that the reduction in the food intake occurs in animals which inhale the cigarette smoke, and induces the disturbance of fetal development in association with CO. In the present study, so as to evaluate the role of energy intake upon the fetal development in utero, the experiment of paired feeding with pregnant rats exposed to cigarette smoke is designed in animals which inhale the cigarette smoke, CO, or room air, following after the observation of the quantity of food taken by mothers exposed to cigarette smoke, CO, or room air.

  8. Use of liposome encapsulated hemoglobin as an oxygen carrier for fetal and adult rat liver cell culture.

    Science.gov (United States)

    Montagne, Kevin; Huang, Hongyun; Ohara, Keikou; Matsumoto, Kunio; Mizuno, Atsushi; Ohta, Katsuji; Sakai, Yasuyuki

    2011-11-01

    Engineering liver tissue constructs with sufficient cell mass for transplantation implies culturing large numbers of hepatocytes in a reduced volume; however, providing sufficient oxygen to dense cell cultures is still not feasible using only conventional culture medium. Liposome-encapsulated hemoglobin (LEH), an oxygen-carrying blood substitute originally designed for short-term perfusion, may be a good candidate as an oxygen carrier to cultured liver cells. In this study, we investigated the feasibility of maintaining long term hepatocyte cultures using LEH. Primary fetal and adult rat liver cells were directly exposed to LEH for 6 to 14 days in static culture or in a perfused flat plate bioreactor. The functions and viability of adult rat hepatocytes exposed to LEH were not adversely affected in static monolayer culture and were even improved in the bioreactor. However, some cytotoxicity of LEH was observed with fetal rat liver cells after 4 days of culture. LEH, though a suitable oxygen carrier for long-term culture of mature hepatocytes, is not suitable in its present form for perfusing fetal hepatocyte cultures in direct contact with the liposomes; either the LEH will have to be made less toxic or a more sophisticated bioreactor that prevents the direct contact between hepatocytes and perfusates will have to be designed if fetal cells are to be used for liver tissue engineering.

  9. [Analysis of sensitivity of stromal stem cells (CFU-f) from rat bone marrow and fetal liver to 5-fluorouracil].

    Science.gov (United States)

    Paiushina, O V; Damaratskaia, E I; Bueverova, E I; Nikonova, T M; Butorina, N N; Molchanova, E A; Starostin, V I

    2006-01-01

    The sensitivity of stromal stem cells (CFU-f) from rat bone marrow and fetal liver to the cytotoxic effect of 5-fluorouracil (5-FU) was compared in vivo and in vitro. Cells from both tissues demonstrated a similar resistance to 5-FU in vitro; however, stromal stem cells from fetal liver proved notably more sensitive to 5-FU compared to marrow CFU-f in vivo. Cells forming colonies of different size were identified in stem cell populations from both tissues. Cells giving rise to small colonies had a higher resistance to 5-FU both in vivo and in vitro.

  10. Fetal rat metabonome alteration by prenatal caffeine ingestion probably due to the increased circulatory glucocorticoid level and altered peripheral glucose and lipid metabolic pathways

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Yansong [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Xu, Dan [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071 (China); Feng, Jianghua, E-mail: jianghua.feng@xmu.edu.cn [Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, 430071 (China); Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen, 361005 (China); Kou, Hao; Liang, Gai [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Yu, Hong; He, Xiaohua; Zhang, Baifang; Chen, Liaobin [Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071 (China); Magdalou, Jacques [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan University, Wuhan, 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan, 430071 (China)

    2012-07-15

    The aims of this study were to clarify the metabonome alteration in fetal rats after prenatal caffeine ingestion and to explore the underlying mechanism pertaining to the increased fetal circulatory glucocorticoid (GC). Pregnant Wistar rats were daily intragastrically administered with different doses of caffeine (0, 20, 60 and 180 mg/kg) from gestational days (GD) 11 to 20. Metabonome of fetal plasma and amniotic fluid on GD20 were analyzed by {sup 1}H nuclear magnetic resonance-based metabonomics. Gene and protein expressions involved in the GC metabolism, glucose and lipid metabolic pathways in fetal liver and gastrocnemius were measured by real-time RT-PCR and immunohistochemistry. Fetal plasma metabonome were significantly altered by caffeine, which presents as the elevated α- and β‐glucose, reduced multiple lipid contents, varied apolipoprotein contents and increased levels of a number of amino acids. The metabonome of amniotic fluids showed a similar change as that in fetal plasma. Furthermore, the expressions of 11β-hydroxysteroid dehydrogenase 2 (11β-HSD-2) were decreased, while the level of blood GC and the expressions of 11β-HSD-1 and glucocorticoid receptor (GR) were increased in fetal liver and gastrocnemius. Meanwhile, the expressions of insulin-like growth factor 1 (IGF-1), IGF-1 receptor and insulin receptor were decreased, while the expressions of adiponectin receptor 2, leptin receptors and AMP-activated protein kinase α2 were increased after caffeine treatment. Prenatal caffeine ingestion characteristically change the fetal metabonome, which is probably attributed to the alterations of glucose and lipid metabolic pathways induced by increased circulatory GC, activated GC metabolism and enhanced GR expression in peripheral metabolic tissues. -- Highlights: ► Prenatal caffeine ingestion altered the metabonome of IUGR fetal rats. ► Caffeine altered the glucose and lipid metabolic pathways of IUGR fetal rats. ► Prenatal caffeine

  11. Analysis of differentially expressed genes in fetal skin of scarless and scar-forming periods of gestational rats

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Objective: To study the differences of gene expression between earlier gestational skin and later gestational skin of rats with the aids of single primer amplification (SPA) and high-density oligonucleotide DNA array to understand the molecular mechanism of scarless healing.Methods: Total RNAs were isolated from fetal rat skin of the scarless (E15) and scar-forming ( E18 ) periods of gestation ( term = 21.5 days). The RNAs from earlier gestational skin (EGS) and later gestational skin (LGS)were both reversely transcribed to cDNAs, then labeled with the incorporation of fluorescent dCTP for preparing the hybridization probes by SPA method. The mixed probes were then hybridized to the oligonucleotide DNA arrays which contained 5 705 probes representing 5 705 rat genes. After highly stringent washing, these DNA arrays were scanned for fluorescent signals to display the differentially expressed genes between the 2 groups of skin.Results: Among 5 705 rat genes, there were 53 genes (0.93 % ) with differentially expressed levels between EGS and LGS groups, 27 genes, including fibroblast growth factor 2 (FGF2) and follistatin were up-regulated (0.47 % ) and 26 genes were down-regulated ( 0.46 % ) in fetal skin during scarless period versus scar-forming period. Higher expressions of FGF2 and follistatin in EGS than those in LGS were also revealed by RT-PCR method. Conclusions: High-density oligonucleotide DNA array provided a powerful tool for investigating differential gene expression in earlier and later gestational fetal skins. This technology validates that the mechanism of fetal scarless healing is very complicate and the change of many gene expressions is associated with fetal scarless healing.

  12. Fetal programming of adult Leydig cell function by androgenic effects on stem/progenitor cells.

    Science.gov (United States)

    Kilcoyne, Karen R; Smith, Lee B; Atanassova, Nina; Macpherson, Sheila; McKinnell, Chris; van den Driesche, Sander; Jobling, Matthew S; Chambers, Thomas J G; De Gendt, Karel; Verhoeven, Guido; O'Hara, Laura; Platts, Sophie; Renato de Franca, Luiz; Lara, Nathália L M; Anderson, Richard A; Sharpe, Richard M

    2014-05-06

    Fetal growth plays a role in programming of adult cardiometabolic disorders, which in men, are associated with lowered testosterone levels. Fetal growth and fetal androgen exposure can also predetermine testosterone levels in men, although how is unknown, because the adult Leydig cells (ALCs) that produce testosterone do not differentiate until puberty. To explain this conundrum, we hypothesized that stem cells for ALCs must be present in the fetal testis and might be susceptible to programming by fetal androgen exposure during masculinization. To address this hypothesis, we used ALC ablation/regeneration to identify that, in rats, ALCs derive from stem/progenitor cells that express chicken ovalbumin upstream promoter transcription factor II. These stem cells are abundant in the fetal testis of humans and rodents, and lineage tracing in mice shows that they develop into ALCs. The stem cells also express androgen receptors (ARs). Reduction in fetal androgen action through AR KO in mice or dibutyl phthalate (DBP) -induced reduction in intratesticular testosterone in rats reduced ALC stem cell number by ∼40% at birth to adulthood and induced compensated ALC failure (low/normal testosterone and elevated luteinizing hormone). In DBP-exposed males, this failure was probably explained by reduced testicular steroidogenic acute regulatory protein expression, which is associated with increased histone methylation (H3K27me3) in the proximal promoter. Accordingly, ALCs and ALC stem cells immunoexpressed increased H3K27me3, a change that was also evident in ALC stem cells in fetal testes. These studies highlight how a key component of male reproductive development can fundamentally reprogram adult hormone production (through an epigenetic change), which might affect lifetime disease risk.

  13. Stem cells decreased neuronal cell death after hypoxic stress in primary fetal rat neurons in vitro.

    Science.gov (United States)

    Sakai, Tetsuro; Xu, Yan

    2012-01-01

    To explore stem cell-mediated neuronal protection through extracellular signaling pathways by transplanted stem cells, we sought to identify potential candidate molecules responsible for neuronal protection using an in vitro coculture system. Primary fetal rat hippocampal neurons underwent hypoxia (≤1% oxygen) for 96 h nad then were returned to a normoxic condition. The study group then received rat umbilical cord matrix-derived stem cells, while the control group received fresh media only. The experimental group showed decreased neuronal apoptosis compared to the control group [44.5 ± 1.6% vs. 71.0 ± 4.2% (mean ± SD, p = 0.0005) on day 5] and higher neuronal survival (4.9 ± 1.2 cells/100× field vs. 2.2 ± 0.3, p = 0.02 on day 5). Among 90 proteins evaluated using a protein array, stem cell coculture media showed increased protein secretion of TIMP-1 (5.61-fold), TIMP-2 (4.88), CNTF-Rα (3.42), activin A (2.20), fractalkine (2.04), CCR4 (2.02), and decreased secretion in MIP-2 (0.30-fold), AMPK α1 (0.43), TROY (0.48), and TIMP-3 (0.50). This study demonstrated that coculturing stem cells with primary neurons in vitro decreased neuronal cell death after hypoxia with significantly altered protein secretion. The results suggest that stem cells may offer neuronal protection through extracellular signaling.

  14. Tobramycin-induced changes in renal histology of fetal and newborn Sprague-Dawley rats.

    Science.gov (United States)

    Mantovani, A; Macrì, C; Stazi, A V; Ricciardi, C; Guastadisegni, C; Maranghi, F

    1992-01-01

    Effects on renal development were studied using tobramycin (TBM) as a model compound. Pregnant Sprague-Dawley rats were injected i.p. with TBM at 30 or 60 mg/kg body weight/day on gestational days (GD) 10-19. Kidneys from dams and conceptuses were examined on GD 20 and on postnatal day (PD) 9. The dosing regimen caused in dams moderate proximal tubular alterations and increased concentrations in serum creatinine. Fetal kidneys showed granularity and swelling of proximal tubule cells at the 30 mg/kg dose, poor glomerular differentiation at the 60 mg/kg dose, increased glomerular density at both doses, and no changes on macroscopic examination at either dose. In newborns were observed a moderate developmental delay and tubular lesions at the higher dose, and dose-related increases of glomerular density and relative medullary area at both doses. All findings were more pronounced in males. A maturational disruption of the tubular structures possibly leading to increased glomerular density was attributed to TBM exposure during renal organogenesis in the rat.

  15. Achillea millefolium inflorescence aqueous extract ameliorates cyclophosphamide-induced toxicity in rat testis: stereological evidences%Achillea millefolium inflorescence aqueous extract ameliorates cyclophosphamide-induced toxicity in rat testis:stereological evidences

    Institute of Scientific and Technical Information of China (English)

    Ali Shalizar Jalali; Shapour Hasanzadeh; Hassan Malekinejad

    2012-01-01

    Cyclophosphamide (CP) is extensively used for the treatment of various cancers,as well as an immunosuppressive agent.However,CP is known to cause several adverse effects including reproductive toxicity.Achillea millefolium,a widely distributed medicinal plant,is highly regarded for its medicinal activities,including antioxidant and anti-inflammatory properties.The present study was conducted to assess whether Achillea millefolium inflorescences aqueous extract with antioxidant and anti-inflammatory activities could serve as a protective agent against reproductive toxicity during CP treatment.Male Wistar rats were categorized into four groups.Two groups of rats were administered CP at a dose of 5mg·kg-1·d-1 for 28 d by oral gavages.One of these groups received Achillea aqueous extract at a dose of 1.2 g·kg-1·d-1 orally 4 h after cyclophosphamide administration.A vehicle treated control group and an Achillea control group were also included.Thc CP-trcatcd group showed significant decreases in the body,testes and epididymides weights as well as many histological alterations.Stereological parameters,spermatogenic activities and testicular antioxidant capacity along with epididymal sperm count and serum testosterone concentration were also significantly decreased by CP treatment.Notably,Achillea co-administration caused a partial recovery in above-mentioned parameters.These findings indicate that Achillea millefolium inflorescence aqueous extract may be partially protective against CP-induced testicular toxicity.

  16. Structural equation modeling and nested ANOVA: Effects of lead exposure on maternal and fetal growth in rats

    Energy Technology Data Exchange (ETDEWEB)

    Hamilton, J.D. (Rohm and Haas Company, Spring House, PA (United States)); O' Flaherty, E.J.; Shukla, R.; Gartside, P.S. (Univ. of Cincinnati, OH (United States)); Ross, R. (Univ. of Cincinnati Medical Center, Cincinnati, OH (United States))

    1994-01-01

    This study provided an assessment of the effects of lead on early growth in rats based on structural equation modeling and nested analysis of variance (ANOVA). Structural equation modeling showed that lead in drinking water (250, 500, or 1000 ppm) had a direct negative effect on body weight and tail length (i.e., growth) in female rats during the first week of exposure. During the following 2 weeks of exposure, high correlation between growth measurements taken over time resulted in reduced early postnatal growth. By the fourth week of exposure, reduced growth was not evident. Mating began after 8 weeks of exposure, and exposure continued during gestation. Decreased fetal body weight was detected when the effects of litter size, intrauterine position, and sex were controlled in a nested ANOVA. Lead exposure did not appear to affect fetal skeletal development, possibly because lead did not alter maternal serum calcium and phosphorus levels. The effect of lead on individual fetal body weight suggests that additional studies are needed to examine the effect of maternal lead exposure on fetal development and early postnatal growth. 24 refs., 4 figs., 6 tabs.

  17. Effect of maternal alcohol and nicotine intake, individually and in combination, on fetal growth in the rat

    Energy Technology Data Exchange (ETDEWEB)

    Leichter, J. (Univ. of British Columbia, Vancouver (Canada))

    1991-03-15

    The effect of maternal ethanol and nicotine administration, separately and in combination, on fetal growth of rats was studied. Nicotine was administered by gavage for the entire gestational period. Alcohol was given in drinking water for 4 weeks prior to mating and 30% throughout gestation. Appropriate pair-fed and ad libitum control animals were included to separate the effect of ethanol and nicotine on the outcome of pregnancy from those produced by the confounding variables of malnutrition. Body weights of fetuses exposed to alcohol alone or in combination with nicotine were significantly lower than those of the pair-fed and ad libitum controls. However, the difference in fetal body weight between the alcohol plus nicotine and the alcohol alone group was not significant. Similarly, in the rats administered nicotine only, fetal weight was not significantly different compared to control animals. The results of this study indicate that maternal alcohol intake impairs fetal growth and nicotine does not, regardless whether it is administered separately or in combination with alcohol for the entire gestational period.

  18. Changes of androgen receptor expression in stages VII-VIII seminiferous tubules of rat testis after exposure to methamphetamine

    OpenAIRE

    Sutita Nudmamud-Thanoi; Nareelak Tangsrisakda; Samur Thanoi

    2016-01-01

    Methamphetamine (METH) is toxic not only to the central nervous system but also to the reproductive system. This study aimed to investigate the effect of METH administration on androgen receptor (AR) expression in the seminiferous tubules (stages VII-VIII) and Leydig cells. 24 Sprague-Dawley rats were equally divided into 4 groups; control, acute doseMETH binge (AB-METH), escalating dose-METH (ED-METH) and escalating dose-METH binge (ED-METH binge) groups. The expressions of AR we...

  19. Correlation between spina bifida manifesta in fetal rats and c-Jun N-terminal kinase signaling

    Institute of Scientific and Technical Information of China (English)

    Yinghuan Ma; Yongxin Bao; Chenghao Li; Fubin Jiao; Hongjie Xin; Zhengwei Yuan

    2012-01-01

    Fetal rat models with neural tube defects were established by injection with retinoic acid at 10 days after conception. The immunofluorescence assay and western blot analysis showed that the number of caspase-3 positive cells in myeloid tissues for spina bifida manifesta was increased. There was also increased phosphorylation of c-Jun N-terminal kinase, a member of the mitogen activated protein kinase family. The c-Jun N-terminal kinase phosphorylation level was positively correlated with caspase-3 expression in myeloid tissues for spina bifida manifesta. Experimental findings indicate that abnormal apoptosis is involved in retinoic acid-induced dominant spina bifida formation in fetal rats, and may be associated with the c-Jun N-terminal kinase signal transduction pathway.

  20. Correlation between spina bifida manifesta in fetal rats and c-Jun N-terminal kinase signaling★

    Science.gov (United States)

    Ma, Yinghuan; Bao, Yongxin; Li, Chenghao; Jiao, Fubin; Xin, Hongjie; Yuan, Zhengwei

    2012-01-01

    Fetal rat models with neural tube defects were established by injection with retinoic acid at 10 days after conception. The immunofluorescence assay and western blot analysis showed that the number of caspase-3 positive cells in myeloid tissues for spina bifida manifesta was increased. There was also increased phosphorylation of c-Jun N-terminal kinase, a member of the mitogen activated protein kinase family. The c-Jun N-terminal kinase phosphorylation level was positively correlated with caspase-3 expression in myeloid tissues for spina bifida manifesta. Experimental findings indicate that abnormal apoptosis is involved in retinoic acid-induced dominant spina bifida formation in fetal rats, and may be associated with the c-Jun N-terminal kinase signal transduction pathway. PMID:25337099

  1. PRKRA Localizes to Nuage Structures and the Ectoplasmic Specialization and Tubulobulbar Complexes in Rat and Mouse Testis

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    Junya Suzuki

    2014-01-01

    Full Text Available The cytoplasmic RNA-induced silencing complex (RISC contains dsRNA binding proteins, including PRKRA, TRBP, and Dicer. RISC localizes to P-bodies. The nuage of the spermatogenic cells has function similar to the P-bodies. We study whether PRKRA localizes to nuage of spermatogenic cells of rat and mouse. PRKRA localized to four types of nuage structures, including aggregates of 60–90 nm particles, irregularly-shaped perinuclear granules, and intermitochondrial cement of pachytene spermatocytes, and chromatoid bodies of round spermatids. In addition, PRKRA is associated with dense material surrounding tubulobulbar complexes and with the ectoplasmic specialization. The results suggest that PRKRA functions in the nuage as an element of RNA silencing system and plays unknown role in the ectoplasmic specialization and at the tubulobulbar complexes of Sertoli cells attaching the head of late spermatids.

  2. The Effect of Zonisamide on Sex Hormones Level and Testis Histological Changes in Adult MaleRat

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    M Mallaki

    2014-01-01

    Full Text Available Abstract Background and aim: Zonisamide is an inhibitor for glutamate neurotransmitter and gamma aminobutiric acid (GABA-mediators. It also increases the total levels of serotonin. According to the importance of this drug in psychotherapy, its side effects on the endocrine system seem to be very important. This study was aimed to determine the effects of zonisamide on pituitary-gonad axis and spermatogenesis. Methods: In this experimental study, 50 adult male Wistar rats were divided in five groups of ten. The control group did not receive any medical treatment. The sham group received 1 ml distilled water as a solvent and three experimental groups were treated with 50, 100, 200 mg/ kg of zonisamide orally for 28 days.At the day of 29, blood samples and preparation of tissue section were taken from all groups. Serum concentrations of hormones were measured via Radio Immuno Assay (RIA. Using the SPSS software, the results were analyzed by using one-way analysis of variance (ANOVA and Tukey tests. Results: The results showed that 100 and 200(mg/kg.b.w of zonisamide could reduce the serum level of testosterone and dihydrotestosterone (DHT, while it increased the LH concentration. It should be noted that 200(mg/kg.b.w of drug also enhanced the FSH level (P<0/001. Also, a considerable decline was observed in spermatogenesis chain at high doses of zonisamide. Conclusion: This study showed that high doses of zonisamide decrease the serum concentration of testosterone and dihydrotestosterone and the number of spermatogenic cells. It also increased the serum FSH and LH levels. Therefore, it is proposed that zonisamide may decrease the function of reproductive activity. Key words: Zonisamide, Reproduction, Rat

  3. TRANSPLANTATION OF CRYOPRESERVED FETAL LIVER CELLS SEEDED INTO MACROPOROUS ALGINATE-GELATIN SCAFFOLDS IN RATS WITH LIVER FAILURE

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    D. V. Grizay

    2015-01-01

    Full Text Available Aim. To study the therapeutic potential of cryopreserved fetal liver cells seeded into macroporous alginategelatin scaffolds after implantation to omentum of rats with hepatic failure.Materials and methods.Hepatic failure was simulated by administration of 2-acetyl aminofl uorene followed partial hepatectomy. Macroporous alginate-gelatin scaffolds, seeded with allogenic cryopreserved fetal liver cells (FLCs were implanted into rat omentum. To prevent from colonization of host cells scaffolds were coated with alginate gel shell. Serum transaminase activity, levels of albumin and bilirubin as markers of hepatic function were determined during 4 weeks after failure model formation and scaffold implantation. Morphology of liver and scaffolds after implantation were examined histologically. Results. Macroporous alginate-gelatin scaffolds after implantation to healthy rats were colonized by host cells. Additional formation of alginate gel shell around scaffolds prevented the colonization. Implantation of macroporous scaffolds seeded with cryopreserved rat FLCs and additionally coated with alginate gel shell into omentum of rats with hepatic failure resulted in signifi cant improvement of hepatospecifi c parameters of the blood serum and positive changes of liver morphology. The presence of cells with their extracellular matrix within the scaffolds was confi rmed after 4 weeks post implantation.Conclusion. The data above indicate that macroporous alginate-gelatin scaffolds coated with alginate gel shell are promising cell carriers for the development of bioengineered liver equivalents.

  4. Effects of Shiga Toxin Type 2 on Maternal and Fetal Status in Rats in the Early Stage of Pregnancy

    Science.gov (United States)

    Sacerdoti, Flavia; Amaral, María M.; Zotta, Elsa; Franchi, Ana M.; Ibarra, Cristina

    2014-01-01

    Shiga toxin type 2 (Stx2), a toxin secreted by Shiga toxin-producing Escherichia coli (STEC), could be one of the causes of maternal and fetal morbimortality not yet investigated. In this study, we examined the effects of Stx2 in rats in the early stage of pregnancy. Sprague-Dawley pregnant rats were intraperitoneally (i.p.) injected with sublethal doses of Stx2, 0.25 and 0.5 ng Stx2/g of body weight (bwt), at day 8 of gestation (early postimplantation period of gestation). Maternal weight loss and food and water intake were analyzed after Stx2 injection. Another group of rats were euthanized and uteri were collected at different times to evaluate fetal status. Immunolocalization of Stx2 in uterus and maternal kidneys was analyzed by immunohistochemistry. The presence of Stx2 receptor (globotriaosylceramide, Gb3) in the uteroplacental unit was observed by thin layer chromatography (TLC). Sublethal doses of Stx2 in rats caused maternal weight loss and pregnancy loss. Stx2 and Gb3 receptor were localized in decidual tissues. Stx2 was also immunolocalized in renal tissues. Our results demonstrate that Stx2 leads to pregnancy loss and maternal morbidity in rats in the early stage of pregnancy. This study highlights the possibility of human pregnancy loss and maternal morbidity mediated by Stx2. PMID:25157355

  5. Effects of Shiga Toxin Type 2 on Maternal and Fetal Status in Rats in the Early Stage of Pregnancy

    Directory of Open Access Journals (Sweden)

    Flavia Sacerdoti

    2014-01-01

    Full Text Available Shiga toxin type 2 (Stx2, a toxin secreted by Shiga toxin-producing Escherichia coli (STEC, could be one of the causes of maternal and fetal morbimortality not yet investigated. In this study, we examined the effects of Stx2 in rats in the early stage of pregnancy. Sprague-Dawley pregnant rats were intraperitoneally (i.p. injected with sublethal doses of Stx2, 0.25 and 0.5 ng Stx2/g of body weight (bwt, at day 8 of gestation (early postimplantation period of gestation. Maternal weight loss and food and water intake were analyzed after Stx2 injection. Another group of rats were euthanized and uteri were collected at different times to evaluate fetal status. Immunolocalization of Stx2 in uterus and maternal kidneys was analyzed by immunohistochemistry. The presence of Stx2 receptor (globotriaosylceramide, Gb3 in the uteroplacental unit was observed by thin layer chromatography (TLC. Sublethal doses of Stx2 in rats caused maternal weight loss and pregnancy loss. Stx2 and Gb3 receptor were localized in decidual tissues. Stx2 was also immunolocalized in renal tissues. Our results demonstrate that Stx2 leads to pregnancy loss and maternal morbidity in rats in the early stage of pregnancy. This study highlights the possibility of human pregnancy loss and maternal morbidity mediated by Stx2.

  6. Fetal Kidney Cells Can Ameliorate Ischemic Acute Renal Failure in Rats through Their Anti-Inflammatory, Anti-Apoptotic and Anti-Oxidative Effects.

    Science.gov (United States)

    Gupta, Ashwani Kumar; Jadhav, Sachin H; Tripathy, Naresh Kumar; Nityanand, Soniya

    2015-01-01

    Fetal kidney cells may contain multiple populations of kidney stem cells and thus appear to be a suitable cellular therapy for the treatment of acute renal failure (ARF) but their biological characteristics and therapeutic potential have not been adequately explored. We have culture expanded fetal kidney cells derived from rat fetal kidneys, characterized them and evaluated their therapeutic effect in an ischemia reperfusion (IR) induced rat model of ARF. The fetal kidney cells grew in culture as adherent spindle shaped/polygonal cells and expressed CD29, CD44, CD73, CD90, CD105, CD24 and CD133 markers. Administration of PKH26 labeled fetal kidney cells in ARF rats resulted in a significant decrease in the levels of blood urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin and decreased tubular necrosis in the kidney tissues (pkidney cells were observed to engraft around injured tubular cells, and there was increased proliferation and decreased apoptosis of tubular cells in the kidneys (pkidney tissues of ARF rats treated with fetal kidney cells had a higher gene expression of renotropic growth factors (VEGF-A, IGF-1, BMP-7 and bFGF) and anti-inflammatory cytokine (IL10); up regulation of anti-oxidative markers (HO-1 and NQO-1); and a lower Bax/Bcl2 ratio as compared to saline treated rats (pkidney cells express mesenchymal and renal progenitor markers, and ameliorate ischemic ARF predominantly by their anti-apoptotic, anti-inflammatory and anti-oxidative effects.

  7. Maternal saturated-fat-rich diet promotes leptin resistance in fetal liver lipid catabolism and programs lipid homeostasis impairments in the liver of rat offspring.

    Science.gov (United States)

    Mazzucco, María Belén; Fornes, Daiana; Capobianco, Evangelina; Higa, Romina; Jawerbaum, Alicia; White, Verónica

    2016-01-01

    We aimed to analyze if an overload of saturated fat in maternal diet induced lipid metabolic impairments in livers from rat fetuses that persist in the offspring and to identify potential mechanisms involving fetal leptin resistance. Female rats were fed either a diet enriched in 25% of saturated fat (SFD rats) or a regular diet (controls). Fetuses of 21days of gestation and offspring of 21 and 140days of age were obtained and plasma and liver were kept for further analysis. Livers from a group of control and SFD fetuses were cultured in the presence or absence of leptin. Leptin or vehicle was administered to control fetuses during the last days of gestation and, on day 21, fetal livers and plasma were obtained. Lipid levels were assessed by thin-layer chromatography and mRNA gene expression of CPT1, ACO and PPARα by RT-PCR. Liver lipid levels were increased and CPT1 and ACO were down-regulated in fetuses and offspring from SFD rats compared to controls. After the culture with leptin, control fetal livers showed increased ACO and CPT1 expression and decreased lipid levels, while fetal livers from SFD rats showed no changes. Fetal administration of leptin induced a decrease in ACO and no changes in CPT1 expression. In summary, our results suggest that a saturated fat overload in maternal diet induces fetal leptin resistance in liver lipid catabolism, which might be contributing to liver lipid alterations that are sustained in the offspring.

  8. Ex vivo culture of human fetal gonads

    DEFF Research Database (Denmark)

    Jørgensen, A; Nielsen, J.E.; Perlman, S

    2015-01-01

    STUDY QUESTION: What are the effects of experimentally manipulating meiosis signalling by addition of retinoic acid (RA) in cultured human fetal gonads? SUMMARY ANSWER: RA-treatment accelerated meiotic entry in cultured fetal ovary samples, while addition of RA resulted in a dysgenetic gonadal...... phenotype in fetal testis cultures. WHAT IS KNOWN ALREADY: One of the first manifestations of sex differentiation is the initiation of meiosis in fetal ovaries. In contrast, meiotic entry is actively prevented in the fetal testis at this developmental time-point. It has previously been shown that RA......-treatment mediates initiation of meiosis in human fetal ovary ex vivo. STUDY DESIGN, SIZE, DURATION: This was a controlled ex vivo study of human fetal gonads treated with RA in 'hanging-drop' tissue cultures. The applied experimental set-up preserves germ cell-somatic niche interactions and the investigated...

  9. Changes of androgen receptor expression in stages VII-VIII seminiferous tubules of rat testis after exposure to methamphetamine

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    Sutita Nudmamud-Thanoi

    2016-06-01

    Full Text Available Methamphetamine (METH is toxic not only to the central nervous system but also to the reproductive system. This study aimed to investigate the effect of METH administration on androgen receptor (AR expression in the seminiferous tubules (stages VII-VIII and Leydig cells. 24 Sprague-Dawley rats were equally divided into 4 groups; control, acute doseMETH binge (AB-METH, escalating dose-METH (ED-METH and escalating dose-METH binge (ED-METH binge groups. The expressions of AR were examined using immunohistochemical staining. AR expressions in round and elongated spermatids showed significant decreases in ED-METH binge and AB-METH groups. In Leydig’s cells, AR expressions were significantly decreased in both ED-METH and ED-METH binge groups. These results could reflect the effect of METH on the expressions of AR in both round and elongated spermatids of stages VII-VIII seminiferous tubule and Leydig’s cells. Decreases of AR expressions in those cells of METH-treated animals may interrupt spermatogenesis at these stages.

  10. Maternal ethanol consumption during pregnancy enhances bile acid-induced oxidative stress and apoptosis in fetal rat liver.

    Science.gov (United States)

    Perez, Maria J; Velasco, Elena; Monte, Maria J; Gonzalez-Buitrago, Jose M; Marin, Jose J G

    2006-08-15

    Ethanol is able to cross the placenta, which may cause teratogenicity. Here we investigated whether ethanol consumption during pregnancy (ECDP), even at doses unable to cause malformation, might increase the susceptibility of fetal rat liver to oxidative insults. Since cholestasis is a common condition in alcoholic liver disease and pregnancy, exposure to glycochenodeoxycholic acid (GCDCA) has been used here as the oxidative insult. The mothers received drinking water without or with ethanol from 4 weeks before mating until term, when placenta, maternal liver, and fetal liver were used. Ethanol induced a decreased GSH/GSSG ratio in these organs, together with enhanced gamma-glutamylcysteine synthetase and glutathione reductase activities in both placenta and fetal liver. Lipid peroxidation in placenta and fetal liver was enhanced by ethanol, although it had no effect on caspase-3 activity. Although the basal production of reactive oxygen species (ROS) was higher by fetal (FHs) than by maternal (AHs) hepatocytes in short-term cultures, the production of ROS in response to the presence of varying GCDCA concentrations was higher in AHs and was further increased by ECDP, which was associated to a more marked impairment in mitochondrial function. Moreover, GCDCA-induced apoptosis was increased by ECDP, as revealed by enhanced Bax-alpha/Bcl-2 ratio (both in AHs and FHs) and the activity of caspase-8 (only in AHs) and caspase-3. In sum, our results indicate that although AHs are more prone than FHs to producing ROS, at doses unable to cause maternal liver damage ethanol consumption causes oxidative stress and apoptosis in fetal liver.

  11. Maternal molecular hydrogen administration ameliorates rat fetal hippocampal damage caused by in utero ischemia-reperfusion.

    Science.gov (United States)

    Mano, Yukio; Kotani, Tomomi; Ito, Mikako; Nagai, Taku; Ichinohashi, Yuko; Yamada, Kiyofumi; Ohno, Kinji; Kikkawa, Fumitaka; Toyokuni, Shinya

    2014-04-01

    Molecular hydrogen (H2) scavenges hydroxyl radicals. Recently, H2 has been reported to prevent a variety of diseases associated with oxidative stress in model systems and in humans. Here, we studied the effects of H2 on rat fetal hippocampal damage caused by ischemia and reperfusion (IR) on day 16 of pregnancy with the transient occlusion of the bilateral utero-ovarian arteries. Starting 2 days before the operation, we provided the mothers with hydrogen-saturated water ad libitum until vaginal delivery. We observed a significant increase in the concentration of H2 in the placenta after the oral administration of hydrogen-saturated water to the mothers, with less placental oxidative damage after IR in the presence of H2. Neonatal growth retardation was observed in the IR group, which was alleviated by the H2 administration. We analyzed the neuronal cell damage in the CA1 and CA3 areas of the hippocampus at day 7 after birth by immunohistochemical analysis of the 8-oxo-7,8-dihydro-2׳-deoxyguanosine- and 4-hydroxy-2-nonenal-modified proteins. Both oxidative stress markers were significantly increased in the IR group, which was again ameliorated by the H2 intake. Last, 8-week-old rats were subjected to a Morris water maze test. Maternal H2 administration improved the reference memory of the offspring to the sham level after IR injury during pregnancy. Overall, the present results support the idea that maternal H2 intake helps prevent the hippocampal impairment of offspring induced by IR during pregnancy. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Cadmium accelerates bone loss in ovariectomized mice and fetal rat limb bones in culture

    Energy Technology Data Exchange (ETDEWEB)

    Bhattacharyya, M.H.; Whelton, B.D.; Stern, P.H.; Peterson, D.P. (Argonne National Lab., IL (USA))

    1988-11-01

    Loss of bone mineral after ovariectomy was studied in mice exposed to dietary cadmium at 0.25, 5, or 50 ppm. Results show that dietary cadmium at 50 ppm increased bone mineral loss to a significantly greater extent in ovariectomized mice than in sham-operated controls. These results were obtained from two studies, one in which skeletal calcium content was determined 6 months after ovariectomy and a second in which {sup 45}Ca release from {sup 45}Ca-prelabeled bones was measured immediately after the start of dietary cadmium exposure. Furthermore, experiments with {sup 45}Ca-prelabeled fetal rat limb bones in culture demonstrated that Cd at 10 nM in the medium, a concentration estimated to be in the plasma of mice exposed to 50 ppm dietary Cd, strikingly increased bone resorption. These in vitro results indicate that cadmium may enhance bone mineral loss by a direct action on bone. Results of the in vivo studies are consistent with a significant role of cadmium in the etiology of Itai-Itai disease among postmenopausal women in Japan and may in part explain the increased risk of postmenopausal osteoporosis among women who smoke.

  13. Development of an artificial neuronal network with post-mitotic rat fetal hippocampal cells by polyethylenimine.

    Science.gov (United States)

    Liu, Bingfang; Ma, Jun; Gao, Erjing; He, Yu; Cui, Fuzhai; Xu, Qunyuan

    2008-03-14

    The selection of appropriate surface materials that promote cellular adhesion and growth is an important consideration when designing a simplified neuronal network in vitro. In the past, extracellular matrix proteins such as laminin (LN) or positively charged substances such as poly-l-lysine (PLL) have been used. In this study, we examined the ability of another positively charged polymer, polyethyleneimine (PEI), to promote neuronal adhesion, growth and the formation of a functional neuronal network in vitro. PEI, PLL and LN were used to produce grid-shape patterns on glass coverslips by micro-contact printing. Post-mitotic neurons from the rat fetal hippocampus were cultured on the different polymers and the viability and morphology of these neurons under serum-free culture conditions were observed using fluorescent microscopy and atomic force microscopy (AFM). We show that neurons cultured on the PEI- and PLL-coated surfaces adhered to and extended neurites along the grid-shape patterns, whereas neurons cultured on the LN-coated coverslips clustered into clumps of cells. In addition, we found that the neurons on the PEI and PLL-coated grids survived for more than 2 weeks in serum-free conditions, whereas most neurons cultured on the LN-coated grids died after 1 week. Using AFM, we observed some neurosynapse-like structures near the neuronal soma on PEI-coated coverslips. These findings indicate that PEI is a suitable surface for establishing a functional neuronal network in vitro.

  14. Biological monitoring of embrio-fetal exposure to methamidophos or chlorothalonil on rat development.

    Science.gov (United States)

    de Castro, V L; Chiorato, S H; Pinto, N F

    2000-12-01

    Maternal exposure to pesticides during the pre-implantation and very early post-implantation periods of pregnancy is correlated with numerous adverse effects on the offspring and in reproductive parameters like an increase in resorption, a decrease in fetal survival and weight, and teratogenic effects. Although the epidemiological evidence is inconclusive as regards the risk of the adverse outcome of pregnancy and developmental toxicity events, the use of biomarkers in exposure assessment may contribute to recognizing a potential health impairment. The present study evaluated the influence of prenatal oral exposure to an insecticide (1.0 mg methamidophos/kg) or a fungicide (200.0 mg chlorothalonil/kg) during gestation days 1 to 6 on maturational and behavioral aspects of offspring development of rats. The pesticides did not affect the body weight gain of dams and offspring, nor did the exposure affect the weight of gravid uterus, fetus, placenta and ovary. There were no observed alterations in the swimming behavior tested at postnatal days 7, 14 and 21, but the pesticides interfered with physical and maturational development landmarks of offspring according to age, showing subtle effects on behavioral and physical development. These findings show the importance of categorizing developmental effects, establishing the relationship between age and important performances, to recognize potential impacts on human populations.

  15. Effect of fetal undernutrition and postnatal overfeeding on rat adipose tissue and organ growth at early stages of postnatal development.

    Science.gov (United States)

    Munoz-Valverde, D; Rodríguez-Rodríguez, P; Gutierrez-Arzapalo, P Y; López de Pablo, A L; Carmen González, M; López-Giménez, R; Somoza, B; Arribas, S M

    2015-01-01

    Intrauterine and perinatal life are critical periods for programming of cardiometabolic diseases. However, their relative role remains controversial. We aimed to assess, at weaning, sex-dependent alterations induced by fetal or postnatal nutritional interventions on key organs for metabolic and cardiovascular control. Fetal undernutrition was induced by dam food restriction (50 % from mid-gestation to delivery) returning to ad libitum throughout lactation (Maternal Undernutrition, MUN, 12 pups/litter). Postnatal overfeeding (POF) was induced by litter size reduction from normally fed dams (4 pups/litter). Compared to control, female and male MUN offspring exhibited: 1) low birth weight and accelerated growth, reaching similar weight and tibial length by weaning, 2) increased glycemia, liver and white fat weights; 3) increased ventricular weight and tendency to reduced kidney weight (males only). Female and male POF offspring showed: 1) accelerated growth; 2) increased glycemia, liver and white fat weights; 3) unchanged heart and kidney weights. In conclusion, postnatal accelerated growth, with or without fetal undernutrition, induces early alterations relevant for metabolic disease programming, while fetal undernutrition is required for heart abnormalities. The progression of cardiac alterations and their role on hypertension development needs to be evaluated. The similarities between sexes in pre-pubertal rats suggest a role of sex-hormones in female protection against programming.

  16. Simultaneous transplantation of fetal ventral mesencephalic tissue and encapsulated genetically modified cells releasing GDNF in a hemi-parkinsonian rat model of Parkinson's disease

    DEFF Research Database (Denmark)

    Perez-Bouza, Alberto; Di Santo, Stefano; Seiler, Stefanie

    2017-01-01

    Transplantation of fetal ventral mesencephalic (VM) neurons for Parkinson's disease (PD) is limited by poor survival and suboptimal integration of grafted tissue into the host brain. In a 6-OHDA rat model of PD we investigated the feasibility of simultaneous transplantation of rat fetal VM tissue...... and polymer-encapsulated C2C12 myoblasts genetically modified to produce glial cell line-derived neurotrophic factor or mocktransfected myoblasts on graft function. Amphetamine-induced rotations were assessed prior and 2, 4, 6 and 9 weeks post-transplantation. We found that rats grafted with VM transplants...

  17. Evaluation of 2-year-old intrasplenic fetal liver tissue transplants in rats.

    Science.gov (United States)

    Lupp, Amelie; Danz, Manfred; Müller, Dieter

    2003-01-01

    Liver cell transplantation into host organs like the spleen may possibly provide a temporary relief after extensive liver resection or severe liver disease or may enable treatment of an enzyme deficiency. With time, however, dedifferentiation or malignant transformation of the ectopically transplanted cells may be possible. Thus, in the present study syngenic fetal liver tissue suspensions were transplanted into the spleen of adult male rats and evaluated 2 years thereafter in comparison to orthotopic livers for histopathological changes and (as markers for preneoplastic transformation) for cytochrome P450 (P450) and glutathione S-transferase (GST) isoform expression. Because inducibility of P450 and GST isoforms may be changed in preneoplastic foci, prior to sacrifice animals were additionally treated either with beta-naphthoflavone, phenobarbital, dexamethasone, or the respective solvent. In the 2-year-old grafts more than 70% of the spleen mass was occupied by the transplant. The transplanted hepatocytes were arranged in cord-like structures. Also few bile ducts were present. Morphologically, no signs of malignancy were visible. With all rats, transplant recipients as well as controls, however, discrete nodular structures were seen in the livers. Due to age, both livers and transplants displayed only a low P450 2B1 and 3A2 and GST class alpha and mu isoform expression. No immunostaining for P450 1A1 was visible. At both sites, beta-naphthoflavone, phenobarbital, or dexamethasone treatment enhanced P450 1A1, P450 2B1 and 3A2, or P450 3A2 expression, respectively. No immunostaining for GST class pi isoforms was seen in the transplants. The livers of both transplant recipients and control rats, however, displayed GST pi-positive foci, corresponding to the nodular structures seen histomorphologically. Compared to the surrounding tissue, these foci also exhibited a more pronounced staining for GST class alpha and mu isoforms and a stronger inducibility of the P450 1A

  18. Contribution of maternal thyroxine to fetal thyroxine pools in normal rats near term

    Energy Technology Data Exchange (ETDEWEB)

    Morreale de Escobar, G.; Calvo, R.; Obregon, M.J.; Escobar Del Rey, F. (Instituto de Investigaciones Biomedicas, Madrid (Spain))

    1990-05-01

    Normal dams were equilibrated isotopically with ({sup 125}I)T4 infused from 11 to 21 days of gestation, at which time maternal and fetal extrathyroidal tissues were obtained to determine their ({sup 125}I)T4 and T4 contents. The specific activity of the ({sup 125}I)T4 in the fetal tissues was lower than in maternal T4 pools. The extent of this change allows evaluation of the net contribution of maternal T4 to the fetal extrathyroidal T4 pools. At 21 days of gestation, near term, this represents 17.5 +/- 0.9% of the T4 in fetal tissues, a value considerably higher than previously calculated. The methodological approach was validated in dams given a goitrogen to block fetal thyroid function. The specific activities of the ({sup 125}I)T4 in maternal and fetal T4 pools were then similar, confirming that in cases of fetal thyroid impairment the T4 in fetal tissues is determined by the maternal contribution. Thus, previous statements that in normal conditions fetal thyroid economy near term is totally independent of maternal thyroid status ought to be reconsidered.

  19. Intrastriatal grafts of fetal ventral mesencephalon improve allodynia-like withdrawal response to mechanical stimulation in a rat model of Parkinson's disease.

    Science.gov (United States)

    Takeda, Ryuichiro; Ishida, Yasushi; Ebihara, Kosuke; Abe, Hiroshi; Matsuo, Hisae; Ikeda, Tetsuya; Koganemaru, Go; Kuramashi, Aki; Funahashi, Hideki; Magata, Yasuhiro; Kawai, Keiichi; Nishimori, Toshikazu

    2014-06-24

    We previously reported that a unilateral 6-hydroxydopamine (6-OHDA) rat model of Parkinson's disease showed allodynia-like withdrawal response to mechanical stimulation of the ipsilateral side of the rat hindpaw. The goal of this study was to investigate the effect of intrastriatal grafts of fetal ventral mesencephalon (VM) on the withdrawal response in 6-OHDA rats. The withdrawal threshold in response to the mechanical stimulation of the rat hindpaw was measured using von Frey filaments. In the ipsilateral side of the 6-OHDA lesions, the withdrawal threshold in response to mechanical stimulation significantly increased in 6-OHDA rats with VM grafts compared with those with sham grafts, but did not change in the contralateral side at 5 weeks after transplantation. The present results suggest that the intrastriatal grafts of fetal VM may relieve pain sensation induced by mechanical stimulation in 6-OHDA rats. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Prenatal testosterone-induced fetal growth restriction is associated with down-regulation of rat placental amino acid transport

    Directory of Open Access Journals (Sweden)

    Hankins Gary DV

    2011-08-01

    Full Text Available Abstract Background Exposure of pregnant mothers to elevated concentrations of circulating testosterone levels is associated with fetal growth restriction and delivery of small-for-gestational-age babies. We examined whether maternal testosterone crosses the placenta to directly suppress fetal growth or if it modifies placental function to reduce the capacity for transport of nutrients to the fetus. Methods Pregnant rats were exposed to testosterone propionate (TP; 0.5 mg/kg by daily subcutaneous injection from gestational days (GD 15-19. Maternal and fetal testosterone levels, placental nutrient transport activity and expression of transporters and birth weight of pups and their anogenital distances were determined. Results This dose of TP doubled maternal testosterone levels but had no effect on fetal testosterone levels. Maternal daily weight gain was significantly lower only on GD 19 in TP treated dams compared to controls. Placental weight and birth weight of pups were significantly reduced, but the anogenital distance of pups were unaffected by TP treatment. Maternal plasma amino acids concentrations were altered following testosterone exposure, with decreases in glutamine, glycine, tyrosine, serine, proline, and hydroxyproline and increases in asparagine, isoleucine, leucine, lysine, histidine and arginine. In the TP dams, placental system A amino acid transport activity was significantly reduced while placental glucose transport capacity was unaffected. Decreased expression of mRNA and protein levels of slc38a2/Snat2, an amino acid transporter, suggests that reduced transporter proteins may be responsible for the decrease in amino acid transport activity. Conclusions Taken together, these data suggest that increased maternal testosterone concentrations do not cross the placenta to directly suppress fetal growth but affects amino acid nutrient delivery to the fetus by downregulating specific amino acid transporter activity.

  1. The Effect of Fetal Olfactory Mucosa on Tissue Sparing and Locomotor Recovery after Spinal Cord Hemisection in Rats

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    Hamdollah Delaviz

    2008-01-01

    Full Text Available Objective: Olfactory ensheathing cells (OECs has been shown to have a neuroprotectiveeffect after transplanted in brain and spinal cord injury (SCI. This study was conductedto determine the possible beneficial results of transplantation of fetal olfactorymucosa (FOM that was the source of OECs in the recovery of locomotor function andin spinal tissue sparing after spinal cord hemisection.Materials and Methods: Forty-eight adult female Sprague-Dawley rats were spinallyhemisected at the L1 level and were randomized into the three groups of 16 animals.The first group, immunosuppressed injured animals were received cyclosporine A (CsAand FOM graft. The second group was received CsA and fetal respiratory mucosa(FRM graft, and the control group; non-immunosuppressed rats were received salineand gel foam. Locomotor performance was assessed weekly for 8 weeks after lesion,using locomotive rating scale developed by Basso, Bresnahan and Beattie (BBB. Afterbehavioral assessment, the spinal cord was examined by a histologist for spinal tissuesparing.Results: From weeks 6-8, the functional recovery of the FOM rats significantly increasedin comparison to the FRM, although a significant difference in tissue sparing was not apparent.From weeks, 2-8 the functional recovery of the FOM and FRM groups as well astissue sparing of the FOM group increased significantly compared to the control group.Conclusion: Thus, the FOM treatment may be effective to promote functional recoveryand partially preserving tissue sparing.

  2. Evidence that active demethylation mechanisms maintain the genome of carcinoma in situ cells hypomethylated in the adult testis

    DEFF Research Database (Denmark)

    Kristensen, D G; Nielsen, J E; Jørgensen, Anne;

    2014-01-01

    cells were assessed by quantitative measurements. The expression of TET1, TET2, APOBEC1, MBD4, APEX1, PARP1, DNMT1, DNMT3A, DNMT3B and DNMT3L in adult testis specimens with CIS and in human fetal testis was investigated by immunohistochemistry and immunofluorescence.Results:DNA from micro-dissected CIS...

  3. In vitro effects of fetal rat cerebrospinal fluid on viability and neuronal differentiation of PC12 cells

    Directory of Open Access Journals (Sweden)

    Nabiuni Mohammad

    2012-06-01

    Full Text Available Abstract Background Fetal cerebrospinal fluid (CSF contains many neurotrophic and growth factors and has been shown to be capable of supporting viability, proliferation and differentiation of primary cortical progenitor cells. Rat pheochromocytoma PC12 cells have been widely used as an in vitro model of neuronal differentiation since they differentiate into sympathetic neuron-like cells in response to growth factors. This study aimed to establish whether PC12 cells were responsive to fetal CSF and therefore whether they might be used to investigate CSF physiology in a stable cell line lacking the time-specific response patterns of primary cells previously described. Methods In vitro assays of viability, proliferation and differentiation were carried out after incubation of PC12 cells in media with and without addition of fetal rat CSF. An MTT tetrazolium assay was used to assess cell viability and/or cell proliferation. Expression of neural differentiation markers (MAP-2 and β-III tubulin was determined by immunocytochemistry. Formation and growth of neurites was measured by image analysis. Results PC12 cells differentiate into neuronal cell types when exposed to bFGF. Viability and cell proliferation of PC12 cells cultured in CSF-supplemented medium from E18 rat fetuses were significantly elevated relative to the control group. Neuronal-like outgrowths from cells appeared following the application of bFGF or CSF from E17 and E19 fetuses but not E18 or E20 CSF. Beta-III tubulin was expressed in PC12 cells cultured in any media except that supplemented with E18 CSF. MAP-2 expression was found in control cultures and in those with E17 and E19 CSF. MAP2 was located in neurites except in E17 CSF when the whole cell was positive. Conclusions Fetal rat CSF supports viability and stimulates proliferation and neurogenic differentiation of PC12 cells in an age-dependent way, suggesting that CSF composition changes with age. This feature may be important

  4. Descent of the testis

    DEFF Research Database (Denmark)

    Hutson, John M.; Thorup, Jørgen M.; Beasley, Spencer W.

    This book provides a state of the art overview of all aspects of testicular descent and cryptorchidism, including the mechanisms of descent and the causes, consequences, diagnosis, and treatment of undescended testis. The advances in understanding that have been achieved over the past two decades...

  5. The undescended testis

    DEFF Research Database (Denmark)

    Vikraman, Jaya; Hutson, John M; Li, Ruili

    2016-01-01

    Undescended testes (UDT), where one or both testes fail to migrate to the base of the scrotum, can be congenital (2-5% of newborn males) or acquired (1-2% of males). The testis may be found in any position along its usual line of descent. Cryptorchidism affects the developing testicular germ cell...

  6. Differentiated cells derived from fetal neural stem cells improve motor deficits in a rat model of Parkinson’s disease

    Institute of Scientific and Technical Information of China (English)

    Wei Wang; Hao Song; Aifang Shen; Chao Chen; Yanming Liu; Yabing Dong; Fabin Han 

    2015-01-01

    Objective:Parkinson’s disease (PD), which is one of the most common neuro‐degenerative disorders, is characterized by the loss of dopamine (DA) neurons in the substantia nigra in the midbrain. Experimental and clinical studies have shown that fetal neural stem cells (NSCs) have therapeutic effects in neurological disorders. The aim of this study was to examine whether cells that were differentiated from NSCs had therapeutic effects in a rat model of PD. Methods:NSCs were isolated from 14‐week‐old embryos and induced to differentiate into neurons, DA neurons, and glial cells, and these cells were characterized by their expression of the following markers:βⅢ‐tubulin and microtubule‐associated protein 2 (neurons), tyrosine hydroxylase (DA neurons), and glial fibrillary acidic protein (glial cells). After a 6‐hydroxydopamine (6‐OHDA)‐lesioned rat model of PD was generated, the differentiated cells were transplanted into the striata of the 6‐OHDA‐lesioned PD rats. Results:The motor behaviors of the PD rats were assessed by the number of apomorphine‐induced rotation turns. The results showed that the NSCs differentiated in vitro into neurons and DA neurons with high efficiencies. After transplantation into the striata of the PD rats, the differentiated cells significantly improved the motor deficits of the transplanted PD rats compared to those of the control nontransplanted PD rats by decreasing the apomorphine‐induced turn cycles as early as 4 weeks after transplantation. Immunofluorescence analyses showed that the differentiated DA neurons survived more than 16 weeks. Conclusions:Our results showed that cells that were differentiated from NSCs had therapeutic effects in a rat PD model, which suggests that differentiated cells may be an effective treatment for patients with PD.

  7. Paternal dapoxetine administration induced deterioration in reproductive performance, fetal outcome, sexual behavior and biochemistry of male rats.

    Science.gov (United States)

    ElMazoudy, R; AbdelHameed, N; ElMasry, A

    2015-01-01

    Dapoxetine, a selective serotonin reuptake inhibitor, is considered an antidepressant drug and has been developed for the treatment of premature ejaculation. Hence the objective was to assess whether dapoxetine administration to male rats adversely affect sexual behavior and pregnancy outcomes after mating with untreated female rats. Proven fertile male rats were gavaged with 0, 2.0, 4.0 and 8.0 mg dapoxetine per kg body weight (bw) per day (DC, DI, DII and DIII groups, respectively) for 70 days prior to mating with untreated female rats. Weight gain, organ weights and feed consumption were decreased significantly in the DII and DIII groups. A significant decline in the number of spermatozoa in the DII and DIII groups is attributed to a significant decrease in testosterone, luteinizing hormone and follicle-stimulating hormone. Levels of prolactin were significantly increased in the DII and DIII groups. Rats treated with a high dose of dapoxetine (8.0 mg kg(-1)) showed a significant inhibition in sperm motility and increment in sperm abnormalities. There was a pronounced decrease in fertility index in females mated with males treated chronically with 4.0 and 8.0 mg per kg bw dapoxetine. In addition, the treatment markedly increased the number of fetal resorptions in female rats impregnated by males in the DII and DIII groups reflecting their infertility. The number of implantation sites and the number of viable fetuses were also notably decreased in female rats impregnated by males given 4.0 or 8.0 mg kg(-1) dapoxetine. These findings suggest that the long-term dapoxetine at high dosages causes failure of the fertilization or successful impregnation of the females mated with dapoxetine-treated male rats, which were clearly able to copulate. A detrimental effect of dapoxetine on fertility parameters was also revealed.

  8. Cadmium and zinc concentrations in fetal and maternal rat tissues after parenteral administration of cadmium during pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Hazelhoff Roelfzema, W.; Roelofsen, A.M.; Herber, R.F.M.; Copius Peereboom-Stegeman, J.H.J.

    1988-10-01

    Cadmium (Cd) and zinc (Zn) concentrations were determined by solid sampling atomic absorption spectrometry (AAS) in rat maternal and fetal tissues after exposure to cadmium. Cadmium was administered subcutaneously as CdCl/sub 2/ in saline daily during pregnancy. Two experiments were performed. In expt. I we investigated the tissue concentration at day 19 (gestational age) after addministration of several doses: 0, 1.1, 2.2, 4.4, and 8.8 ..mu..mol Cd/kg/day. In expt. II the course of the Cd and Zn concentrations during pregnancy was investigated by collecting samples at days 14, 16, 18 and 20, after daily injections of 4.4 ..mu..mol Cd/kg. Cadmium concentrations in blood, maternal liver, placenta and fetal liver increased with dose and duration of exposure. Cadmium was heavily accumulated in the liver and transferred to the fetus only in small amounts. The zinc concentration in the maternal liver was positively correlated with the cadmium concentration. In the placenta the zinc concentration was not affected. Zinc in fetal liver was decreased from day 18 onward. Despite relatively high cadmium levels and decreased zinc levels in the fetus, we observed no adverse effects on various reproduction parameters, such as birth weights and obvious malformations.

  9. 1,25(OH) sub 2 D sub 3 and Ca-binding protein in fetal rats: Relationship to the maternal vitamin D status

    Energy Technology Data Exchange (ETDEWEB)

    Verhaeghe, J.; Thomasset, M.; Brehier, A.; Van Assche, F.A.; Bouillon, R. (Katholieke Universiteit Leuven (Belgium) Institut National de la Sante et de la Recherche Medical (France))

    1988-04-01

    The autonomy and functional role of fetal 1,25-dihydroxyvitamin D{sub 3} (1,25(OH){sub 2}D{sub 3}) were investigated in nondiabetic and diabetic BB rats fed diets containing 0.85% calcium-0.7% phosphorus or 0.2% calcium and phosphorus and in semistarved rats on the low calcium-phosphorus diet. The changes in maternal and fetal plasma 1,25(OH){sub 2}D{sub 3} were similar: the levels were increased by calcium-phosphorus restriction and decreased by diabetes and semistarvation. Maternal and fetal 1,25(OH){sub 2}D{sub 3} levels were correlated. The vitamin D-dependent calcium-binding proteins (CaBP{sub 9K} and CaBP{sub 28K}) were measured in multiple maternal and fetal tissues and in the placenta of nondiabetic, diabetic, and calcium-phosphorus-restricted rats. The distributions of CaBP{sub 9K} and CaBP{sub 28K} in the pregnant rat were similar to that of the growing rat. The increased maternal plasma 1,25(OH){sub 2}D{sub 3} levels in calcium-phosphorus-restricted rats were associated with higher duodenal CaBP{sub 9K} and renal CaBPs, but placental CaBP{sub 9K} was not different. In diabetic pregnant rats, duodenal CaBP{sub 9K} was not different. In diabetic pregnant rats, duodenal CaBP{sub 9K} tended to be lower, while renal CaBPs were normal; placental CaBP{sub 9K} was decreased. The results indicate that in the rat fetal 1,25(OH){sub 2}D{sub 3} depends on maternal 1,25(OH){sub 2}D{sub 3} or on factors regulating maternal 1,25(OH){sub 2}D{sub 3}. The lack of changes in fetal CaBP in the presence of altered fetal plasma 1,25(OH){sub 2}D{sub 3} levels confirms earlier data showing that 1,25(H){sub 2}D{sub 3} has a limited hormonal function during perinatal development in the rat.

  10. Inulin supplementation during gestation mitigates acrylamide-induced maternal and fetal brain oxidative dysfunctions and neurotoxicity in rats.

    Science.gov (United States)

    Krishna, Gokul; Muralidhara

    2015-01-01

    Accumulating evidence suggests that the developing brain is more susceptible to a variety of chemicals. Recent studies have shown a link between the enteric microbiota and brain function. While supplementation of non-digestible oligosaccharides during pregnancy has been demonstrated to positively influence human health mediated through stimulation of beneficial microbiota, our understanding on their neuromodulatory propensity is limited. In the present study, our primary focus was to examine whether supplementation of inulin (a well known fructan) during gestation can abrogate acrylamide (ACR)-induced oxidative impairments and neurotoxicity in maternal and fetal brain of rats. Initially, in a dose-determinative study, we recapitulated the impact of ACR exposure during gestation days (GD 6-19) on gestational parameters, extent of oxidative impairments in brain (maternal/fetal), cholinergic function and neurotoxicity. Subsequently, pregnant rats orally (gavage) administered with inulin (IN, 2 g/kg/day in two equal installments) supplements during gestation days (GD 0-19) were exposed to ACR (200 ppm) in drinking water. IN supplements significantly attenuated ACR-induced changes in exploratory activity (reduced open field exploration) measured on GD 14. Further, IN restored the placental weights among ACR exposed dams. Analysis of biochemical markers revealed that IN supplements effectively offset ACR associated oxidative stress not only in the maternal brain, but in the fetal brain as well. Elevated levels of protein carbonyls in maternal brain regions were completely normalized with IN supplements. More importantly, IN supplements significantly augmented the number of Bifidobacteria in the cecum of ACR rats which correlated well with the neurorestorative effect as evidenced by restored dopamine levels in the maternal cortex and fetal brain acetylcholinesterase activity among ACR-exposed dams. Further, IN supplements also conferred significant protection against

  11. Effect of nebivolol treatment during pregnancy on the genital circulation, fetal growth and postnatal development in the Wistar rat.

    Science.gov (United States)

    Altoama, Kassem; Yassine Mallem, Mohamed; Thorin, Chantal; Betti, Eric; Desfontis, Jean-Claude

    2015-07-05

    The aim of study was to evaluate the effects of nebivolol, a cardioselective beta-1 adrenergic receptor blocker of the third generation with vasodilatory properties, vs. bisoprolol on the genital circulation, uterine vasculature, fetal growth and postnatal development in pregnant Wistar rats. Non invasive measurements of systolic and diastolic blood pressure (SBP and DBP) and heart rate (HR), and invasive measurement of genital blood flow (GBF) were taken in pregnant rats, by tail cuff and transonic probe methods respectively, after an oral treatment by gastric gavage with nebivolol (8mg/kg/day) or bisoprolol (10mg/kg/day) from day 11 to day 18 of pregnancy. Other morphometrical and histological measurements were performed on the ovarian and uterine arteries to evaluate the effect of nebivolol on the uterine vasculature. Furthermore, postnatal mortality and pup growth were recorded. The data demonstrated that nebivolol (compared with bisoprolol) induced a significant decrease in SBP, HR and GBF while DBP remained unchanged. Moreover, nebivolol increased the diameter and the length of ovarian and uterine arteries and the number of uterine artery segmental branches. The results also showed that the body weight gain of newborns in the nebivolol group was significantly lower vs. bisoprolol and vs. control with a higher mortality rate. The nebivolol action is not only limited to its favorable hemodynamic effects represented by a decrease in blood pressure, but it also produces adverse effects on fetal growth and postnatal development that may limit its therapeutic use in females during pregnancy.

  12. Fetal and neonatal nicotine exposure in Wistar rats causes progressive pancreatic mitochondrial damage and beta cell dysfunction.

    Directory of Open Access Journals (Sweden)

    Jennifer E Bruin

    Full Text Available Nicotine replacement therapy (NRT is currently recommended as a safe smoking cessation aid for pregnant women. However, fetal and neonatal nicotine exposure in rats causes mitochondrial-mediated beta cell apoptosis at weaning, and adult-onset dysglycemia, which we hypothesize is related to progressive mitochondrial dysfunction in the pancreas. Therefore in this study we examined the effect of fetal and neonatal exposure to nicotine on pancreatic mitochondrial structure and function during postnatal development. Female Wistar rats were given saline (vehicle control or nicotine bitartrate (1 mg/kg/d via subcutaneous injection for 2 weeks prior to mating until weaning. At 3-4, 15 and 26 weeks of age, oral glucose tolerance tests were performed, and pancreas tissue was collected for electron microscopy, enzyme activity assays and islet isolation. Following nicotine exposure mitochondrial structural abnormalities were observed beginning at 3 weeks and worsened with advancing age. Importantly the appearance of these structural defects in nicotine-exposed animals preceded the onset of glucose intolerance. Nicotine exposure also resulted in significantly reduced pancreatic respiratory chain enzyme activity, degranulation of beta cells, elevated islet oxidative stress and impaired glucose-stimulated insulin secretion compared to saline controls at 26 weeks of age. Taken together, these data suggest that maternal nicotine use during pregnancy results in postnatal mitochondrial dysfunction that may explain, in part, the dysglycemia observed in the offspring from this animal model. These results clearly indicate that further investigation into the safety of NRT use during pregnancy is warranted.

  13. Grafts of fetal locus coeruleus neurons in rat amygdala-piriform cortex suppress seizure development in hippocampal kindling.

    Science.gov (United States)

    Barry, D I; Wanscher, B; Kragh, J; Bolwig, T G; Kokaia, M; Brundin, P; Björklund, A; Lindvall, O

    1989-11-01

    Hippocampal kindling was investigated in rats with a 6-hydroxydopamine-induced lesion of the forebrain catecholamine system after implantation of neural tissue from the fetal locus coeruleus region either bilaterally into the amygdala-piriform cortex (i.e., distant to the kindling site) or unilaterally into the hippocampus (close to the kindling site). Lesioned animals with either sham grafts or control grafts consisting of fetal striatal tissue showed a kindling rate much faster than that of normal controls. In contrast, in rats with bilateral locus coeruleus grafts in the amygdala-piriform cortex (implanted at three sites) the development of seizures was similar to that of controls and significantly slower than that in lesioned animals with sham grafts. All these animals had bilateral surviving grafts with a mean of 125 noradrenergic cells per implantation site. In the animals with locus coeruleus grafts in the stimulated hippocampus the kindling rate did not differ from that in the lesioned animals with control grafts. Most of these animals had large surviving grafts and showed a dense noradrenergic reinnervation of the implanted hippocampus. The present findings indicate that grafting of fetal pontine tissue (rich in noradrenergic neurons) to a site distant to the stimulation focus, but important for the generalization and spread of seizures, can retard the development of seizures in hippocampal kindling. Together with the data of our previous report this study also indicates that noradrenergic reinnervation of both hippocampi is important for the seizure-suppressant action in hippocampal kindling of locus coeruleus grafts implanted in the hippocampus.

  14. Developmental changes in glutathione S-transferase isoforms expression and activity in intrasplenic fetal liver tissue transplants in rats.

    Science.gov (United States)

    Lupp, Amelie; Anschütz, Tino; Lindström-Seppä, Pirjo; Müller, Dieter

    2003-09-01

    The aim of the present study was to characterise developmental changes in glutathione S-transferase (GST) isoforms expression and in glutathione conjugation capacity in intrasplenic liver tissue transplants. For this purpose, syngenic fetal liver tissue suspensions were transplanted into the spleens of adult male Fischer 344 rats. Three days, 1, 2, 4 weeks, 2, 4, 6 months and 1 year later, transplant-recipients and control animals were sacrificed and class alpha, mu and pi GST isoforms expression and GST activities using the substrates o-dinitrobenzene and 1-chloro-2,4-dinitrobenzene were assessed in livers and spleens. In the hepatocytes of the adult livers no class pi, but a distinct class alpha and mu GST expression was seen. The bile duct epithelia were class pi GST positive. Fetal livers displayed almost no class alpha and mu, but a slight class pi GST expression. The same pattern was seen in 3-day-old intrasplenic liver tissue transplants. Up to 2 weeks after surgery the class alpha and mu GST expression increased in the hepatocytes of the transplants, whereas the immunostaining for class pi GST disappeared. No remarkable changes were seen thereafter. Normal conjugation capacities were observed with the livers of both groups of rats. Control spleens displayed only low GST activities. From 2 months after transplantation on activities were significantly higher in transplant-containing spleens than in respective control organs with a further increase up to one year after grafting. These results show that intrasplenically transplanted fetal liver cells proliferate and differentiate into mature cells displaying a GST expression pattern with respective enzyme activities similar to adult liver.

  15. Towards a rational terminology in the study of the gubernaculum testis: arguments in support of the notion that the cremasteric sac should be considered the gubernaculum in postnatal rats and other mammals

    NARCIS (Netherlands)

    P. van der Schoot

    1996-01-01

    textabstractThere is need for a consistent definition of structures caudal to the testis that variously are termed 'gubernaculum testis' as a basis for understanding the emergence and sexually dimorphic further growth and differentiation of this specifically mammalian s

  16. Towards a rational terminology in the study of the gubernaculum testis: arguments in support of the notion that the cremasteric sac should be considered the gubernaculum in postnatal rats and other mammals

    NARCIS (Netherlands)

    P. van der Schoot

    1996-01-01

    textabstractThere is need for a consistent definition of structures caudal to the testis that variously are termed 'gubernaculum testis' as a basis for understanding the emergence and sexually dimorphic further growth and differentiation of this specifically mammalian

  17. Electroporation of the Testis

    Science.gov (United States)

    Yomogida, Kentaro

    The mature mammalian testis is a marvelous organ that produces numerous sperm cells during its reproductive phase. This biologically significant process consists of three steps: stem cell self-renewal and differentiation, meiosis and genetic recombination, and haploid cell morphogenesis into sperm (Russell et al., 1990). The first step provides a good model for investigating the molecular mechanism of stem cell regulation. Currently, the mechanism underlying sperm cell production is a very exciting topic in regenerative medicine (Lensch et al. 2007; Okita et al., 2007). The spermatogonial stem cell system has several advantages, including the easy histological identification of stem cells (Russell et al., 1990), a clear relationship between stem cells and the supporting Sertoli cells, which provide a stem cell niche (Tadokoro et al., 2002; Yomogida et al., 2003), and a transplantation assay for stem cell activity (Oatley & Brinster, 2006). Although germline stem (GS) cells derived from the gonocytes in newborn testis constitute a suitable in vitro system for investigating the properties of spermatogonial stem cells (Kanatsu-Shinohara et al., 2003, 2004), studies using living mammalian testes continue to provide information regarding the roles of the stem cell niche. In vivo electroporation of the supporting cells in the testis will expand our ability to study it.

  18. Steroidogenesis in fetal male rats is reduced by DEHP and DINP, but endocrine effects of DEHP are not modulated by DEHA in fetal, prepubertal and adult male rats

    DEFF Research Database (Denmark)

    Boberg, Julie; Ladefoged, Ole; Hass, Ulla

    2004-01-01

    with DEHA and DINP have led to the hypothesis that similarities inaction may also exist. Pregnant Wistar rats were gavaged during gestation and lactation with vehicle, DEHP (300 or 750 mg/kg bodyweight per day), DINP (750 mg/kg bodyweight per day), DEHP (750 mg/kg bodyweight per day) in combination...

  19. Comparison of rat and rabbit embryo-fetal developmental toxicity data for 379 pharmaceuticals: on the nature and severity of developmental effects.

    Science.gov (United States)

    Theunissen, Peter T; Beken, Sonja; Beyer, Bruce K; Breslin, William J; Cappon, Gregg D; Chen, Connie L; Chmielewski, Gary; De Schaepdrijver, Luc; Enright, Brian; Foreman, Jennifer E; Harrouk, Wafa; Hew, Kok-Wah; Hoberman, Alan M; Hui, Julia Y; Knudsen, Thomas B; Laffan, Susan B; Makris, Susan L; Martin, Matt; McNerney, Mary Ellen; Siezen, Christine L; Stanislaus, Dinesh J; Stewart, Jane; Thompson, Kary E; Tornesi, Belen; Van der Laan, Jan Willem; Weinbauer, Gerhard F; Wood, Sandra; Piersma, Aldert H

    2016-11-01

    Regulatory non-clinical safety testing of human pharmaceuticals typically requires embryo-fetal developmental toxicity (EFDT) testing in two species (one rodent and one non-rodent). The question has been raised whether under some conditions EFDT testing could be limited to one species, or whether the testing in a second species could be decided on a case-by-case basis. As part of a consortium initiative, we built and queried a database of 379 compounds with EFDT studies (in both rat and rabbit animal models) conducted for marketed and non-marketed pharmaceuticals for their potential for adverse developmental and maternal outcomes, including EFDT incidence and the nature and severity of adverse findings. Manifestation of EFDT in either one or both species was demonstrated for 282 compounds (74%). EFDT was detected in only one species (rat or rabbit) in almost a third (31%, 118 compounds), with 58% (68 compounds) of rat studies and 42% (50 compounds) of rabbit studies identifying an EFDT signal. For 24 compounds (6%), fetal malformations were observed in one species (rat or rabbit) in the absence of any EFDT in the second species. In general, growth retardation, fetal variations, and malformations were more prominent in the rat, whereas embryo-fetal death was observed more often in the rabbit. Discordance across species may be attributed to factors such as maternal toxicity, study design differences, pharmacokinetic differences, and pharmacologic relevance of species. The current analysis suggests that in general both species are equally sensitive on the basis of an overall EFDT LOAEL comparison, but selective EFDT toxicity in one species is not uncommon. Also, there appear to be species differences in the prevalence of various EFDT manifestations (i.e. embryo-fetal death, growth retardation, and dysmorphogenesis) between rat and rabbit, suggesting that the use of both species has a higher probability of detecting developmental toxicants than either one alone.

  20. Intrauterine Growth Restricted Rats Exercised at Pregnancy: Maternal-Fetal Repercussions.

    Science.gov (United States)

    Corvino, S B; Netto, A O; Sinzato, Y K; Campos, K E; Calderon, I M P; Rudge, M V C; Volpato, G T; Zambrano, E; Damasceno, D C

    2015-08-01

    To evaluate the effect of swimming in pregnant rats born with intrauterine growth restriction (IUGR) and their offspring, IUGR rats were obtained using the streptozotocin-induced severe diabetic (SD) rats. In this study, the nondiabetic parental generation presented 10 rats and diabetic parental generation presented 116 rats. Of these, the mated nondiabetic female rats were 10 and the number of diabetic rats was 45. In relation to term pregnancy, there were 10 animals in the nondiabetic group and 15 rats in the diabetic group. In the offspring of SD rats (IUGR group), 43 females were classified as small for pregnancy age, 19 rats were classified as appropriate for pregnancy age, and 0 female was classified as large for pregnancy age. The nondiabetic and SD pregnant rats generated offspring with appropriate (control [C]) and small (IUGR) weight for pregnancy age, respectively. At adult life, the C group was maintained as nonexercised C group and IUGR rats were distributed into 2 subgroups, namely, nonexercised (IUGR) and exercised (IUGRex). The rate of mated rats in the IUGR group was reduced compared to the C group. During pregnancy, the IUGR rats presented hyperinsulinemia, impaired reproductive outcomes, decreased body weight, hypertriglyceridemia, and hyperlactacidemia. The IUGRex presented reduced insulin and triglyceride levels. Thus, swimming improved lipid metabolism and increased insulin sensitivity. However, the offspring showed retarded growth, reinforcing the need to stimulate the exercise practice in women under supervision with different professional expertise to promote appropriate gestational conditions and improve perinatal outcomes. © The Author(s) 2015.

  1. Nicotine-induced retardation of chondrogenesis through down-regulation of IGF-1 signaling pathway to inhibit matrix synthesis of growth plate chondrocytes in fetal rats

    Energy Technology Data Exchange (ETDEWEB)

    Deng, Yu; Cao, Hong; Cu, Fenglong [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Xu, Dan [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Lei, Youying [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Tan, Yang [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Magdalou, Jacques [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Wang, Hui [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Chen, Liaobin, E-mail: lbchen@whu.edu.cn [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China)

    2013-05-15

    Previous studies have confirmed that maternal tobacco smoking causes intrauterine growth retardation (IUGR) and skeletal growth retardation. Among a multitude of chemicals associated with cigarette smoking, nicotine is one of the leading candidates for causing low birth weights. However, the possible mechanism of delayed chondrogenesis by prenatal nicotine exposure remains unclear. We investigated the effects of nicotine on fetal growth plate chondrocytes in vivo and in vitro. Rats were given 2.0 mg/kg·d of nicotine subcutaneously from gestational days 11 to 20. Prenatal nicotine exposure increased the levels of fetal blood corticosterone and resulted in fetal skeletal growth retardation. Moreover, nicotine exposure induced the inhibition of matrix synthesis and down-regulation of insulin-like growth factor 1 (IGF-1) signaling in fetal growth plates. The effects of nicotine on growth plates were studied in vitro by exposing fetal growth plate chondrocytes to 0, 1, 10, or 100 μM of nicotine for 10 days. Nicotine inhibited matrix synthesis and down-regulated IGF-1 signaling in chondrocytes in a concentration-dependent manner. These results suggest that prenatal nicotine exposure induces delayed chondrogenesis and that the mechanism may involve the down-regulation of IGF-1 signaling and the inhibition of matrix synthesis by growth plate chondrocytes. The present study aids in the characterization of delayed chondrogenesis caused by prenatal nicotine exposure, which might suggest a candidate mechanism for intrauterine origins of osteoporosis and osteoarthritis. - Highlights: ► Prenatal nicotine-exposure could induce delayed chondrogenesis in fetal rats. ► Nicotine inhibits matrix synthesis of fetal growth plate chondrocytes. ► Nicotine inhibits IGF-1 signaling pathway in fetal growth plate chondrocytes.

  2. Effect of Morus nigra aqueous extract treatment on the maternal-fetal outcome, oxidative stress status and lipid profile of streptozotocin-induced diabetic rats

    OpenAIRE

    Volpato, Gustavo Tadeu; Calderon, Iracema Mattos Paranhos; Sinzato, S. [UNESP; de Campos, Kleber Eduardo; Rudge, Marilza Vieira Cunha [UNESP; Damasceno,Débora Cristina

    2011-01-01

    Ethnopharmacological relevance: Morus nigra, commonly known as black mulberry, is widely used in Brazilian folk medicine for the diabetes treatment.Aim of this study: To evaluate the effect of Morus nigra aqueous extract treatment on maternal lipid and oxidative stress profile, reproductive outcomes, and also fetal anomaly incidence from diabetic and non-diabetic rats.Materials and methods: Diabetes was induced by streptozotocin (40 mg/kg) in virgin female Wistar rats. Morus nigra leaf aqueou...

  3. Experimental study on cleft palate repair of rat using rat fetal membrane%鼠胎膜修复大鼠腭裂的实验研究

    Institute of Scientific and Technical Information of China (English)

    张驰; 娜荷雅; 张幸竹; 王丝墨; 唐喜乐; 马振宇; 肖晶; 李武伟

    2013-01-01

    目的 以鼠胎膜对腭裂进行整复手术,研究修复腭裂的效果.方法 建立腭裂动物模型实验.30只SD大鼠按照腭部裂隙大小分为3组,每组10只.a组:长7 mm×宽0.9 mm;b组:长7 mm×宽1.1 mm;c组:长7mm×宽1.3 mm.术后12周处死所有大鼠,观察裂隙变化.手术关闭裂隙实验.10只SD大鼠分为3组.A组大鼠5只,手术造腭裂并以新鲜双层胎膜关闭裂隙;B组大鼠3只,手术造腭裂,令裂隙自行生长;C组2只作为空白对照组.术后4周处死动物,大体观察;制作切片,行组织学观察.结果 腭裂动物模型成功建立,确立b组7mm×1.1 mm为临界缺损.A组大鼠腭裂得到成功修复,口鼻腔黏膜分别愈合,完全覆盖腭裂,镜下见腭裂处口腔黏膜层次清楚,存在黏膜下层,顶部有完整的鼻腔黏膜.结论 鼠胎膜对SD大鼠腭裂具有良好的修复效果.%Objective To explore the feasibility of repairing the defect in cleft palate using fetal membrane in a rat model. Methods To establish the animal model of cleft palate. Thirty SD rats were randomly divided into three groups with 10 rats in each group according to the different size of man - made cleft, group a: 7 mm × 0. 9 mm, group b: 7 mm × 1. 1 mm, group c: 7 mm × 1.3 mm. Animals were sacrificed at the end of 12 weeks and the changes of clefts were compared. Repairing experiment for cleft palate. Ten SD rats were randomly divided into three groups, group A was underwent reduction with 5 rats, group B was only performed model operation with 3 rats, group C was blank with 2 rats. All rats were sacrificed at the end of 4 weeks and the gross and histological observation was respectively carried out. Results The animal model of cleft palate was successfully established. Group b was determined to be the animal model group for critical - sized defect. Cleft palate was repaired successfully in group A with fetal membrane of rat, the structure of palate mucosa was similar to that of the group C in gross

  4. Identification of a novel testis-specific gene and its potential roles in testis development/spermatogenesis

    Institute of Scientific and Technical Information of China (English)

    Lan-Lan Yin; Jian-Min Li; Zuo-Min Zhou; Jia-Hao Sha

    2005-01-01

    Aim: To identify and characterize a novel gene with potential roles in testis development and spermatogenesis.Methods: A cDNA microarray was constructed from a human testis large insert cDNA library and hybridized with probes of human or mouse adult and fetal testes. Differentially expressed genes were isolated and sequenced. RT-PCR was used to test the tissue distribution of the genes of interest and in situ hybridization was performed to localize the gene expression in the mouse testis. A range of bioinformatical programs including Gene Runner, SMART, NCBI Blast and Emboss CpGPlot were used to characterize the new gene's feature. Results: A novel testis-specific gene,NYD-SP5, was differentially expressed in fetal and adult testes. The deduced protein structure of NYD-SP5 was found to contain an IQ motif (a short calmodulin-binding motif containing conserved Ile and Gln residues), a Carbamate kinase-like domain, a Zn-dependent exopeptidase domain and a lactate dehydrogenase (LDH) C-terminal-like domain. RT-PCR analysis revealed that NYD-SP5 was predominantly expressed in the testis but not in other 15 tissues examined. In situ hybridization and RT-PCR examinations revealed that the expression of NYD-SP5 was confined in the male germ cell but not present in the somatic cell in the testes. Conclusion: NYD-SP5 is a newly found testisspecific gene with potential roles in testis development and spermatogenesis through a calmodulin-activated enzyme.

  5. Comparing rat and rabbit embryo-fetal developmental toxicity studies for 379 pharmaceuticals: On systemic dose and developmental effects (Critical Reviews in Toxicology)

    Science.gov (United States)

    A database of embryo-fetal developmental toxicity (EFDT) studies of 379 pharmaceutical compounds in rat and rabbit was analyzed for species differences based on toxicokinetic parameters of area under the curve (AUC) and maximum concentration (Cmax) at the developmental adverse ef...

  6. Comparison of rat and rabbit embryo-fetal developmental toxicity data for 379 pharmaceuticals: on the nature and severity of developmental effects (Critical Reviews in Toxicology)

    Science.gov (United States)

    Regulatory non-clinical safety testing of human pharmaceutical compounds typically requires embryo fetal developmental toxicity (EFDT) testing in two species, (one rodent and one non-rodent, usually the rat and the rabbit). The question has been raised whether under some conditio...

  7. c-Yes regulates cell adhesion at the blood-testis barrier and the apical ectoplasmic specialization in the seminiferous epithelium of rat testes.

    Science.gov (United States)

    Xiao, Xiang; Mruk, Dolores D; Lee, Will M; Cheng, C Yan

    2011-04-01

    During spermatogenesis, extensive junction restructuring takes place at the blood-testis barrier (BTB) and the Sertoli cell-spermatid interface known as the apical ectoplasmic specialization (apical ES, a testis-specific adherens junction) in the seminiferous epithelium. However, the mechanism(s) that regulates these critical events in the testis remains unknown. Based on the current concept in the field, changes in the phosphorylation status of integral membrane proteins at these sites can induce alterations in protein endocytosis and recycling, causing junction restructuring. Herein, c-Yes, a non-receptor protein tyrosine kinase, was found to express abundantly at the BTB and apical ES stage-specifically, coinciding with junction restructuring events at these sites during the seminiferous epithelial cycle of spermatogenesis. c-Yes also structurally associated with adhesion proteins at the BTB (e.g., occludin and N-cadherin) and the apical ES (e.g., β1-integrin, laminins β3 and γ3), possibly to regulate phosphorylation status of proteins at these sites. SU6656, a selective c-Yes inhibitor, was shown to perturb the Sertoli cell tight junction-permeability barrier in vitro, which is mediated by changes in the distribution of occludin and N-cadherin at the cell-cell interface, moving from cell surface to cytosol, thereby destabilizing the tight junction-barrier. However, this disruptive effect of SU6656 on the barrier was blocked by testosterone. Furthermore, c-Yes is crucial to maintain the actin filament network in Sertoli cells since a blockade of c-Yes by SU6656 induced actin filament disorganization. In summary, c-Yes regulates BTB and apical ES integrity by maintaining proper distribution of integral membrane proteins and actin filament organization at these sites.

  8. The fetal programming of dietary fructose and saturated fat on hepatic quercetin glucuronidation in rats

    Science.gov (United States)

    Objective Phase II biotransformation of flavonoids generates bioactive metabolites in vivo. However, data on the effect of environmental and physiological factors and fetal programming on phase II pathways toward flavonoids are limited. We examined the effect of parental exposure to a diet high in s...

  9. In utero glucocorticoid (GLC) exposure reduces fetal skeletal muscle growth in rats

    Science.gov (United States)

    Maternal undernutrition and stress expose the fetus to above normal levels of GLC and predispose to intrauterine growth restriction. The aim of this study was to determine if fetal GLC exposure impairs skeletal muscle growth independently of maternal undernutrition. Three groups (n=7/group) of timed...

  10. Expression of a novel pyridoxal kinase mRNA splice variant, PKH-T, in human testis

    Institute of Scientific and Technical Information of China (English)

    XingFang; Zuo-MinZhou; LiLu; Lan-LanYin; Jian-MinLi; YinZhen; HuiWang; Jia-HaoSha

    2004-01-01

    Aim: To identify the genes specifically expressed in human adult and fetal testes and spermatozoa.Methods: A human testis cDNA microarray was established. Then mRNAs of human adult and fetal testis and spermatozoa were purified and probes were prepared by a reverse transcription reaction with mRNA as the template.The microarray was hybridized with probes of adult and fetal testes and spermatozoa. The nucleic acid sequences of differentially expressed genes were determined and homologies were searched in the databases of GenBank. Results:A novel human testis-specific gene, PKH-T, was identified by hybridizing adult and fetal testis and spermatozoa probes with a human testis cDNA microarray. The cDNA of PKH-T was 1069 bp in length. The cDNA sequence of this clone was deposited in the Genbank (AY303972) and PKH-T was also determined as Interim GenSymbol (Unigene,HS.38041). PKH-T contained most PKH conserved motif. The 239 amino acid sequences deduced from the 719 bp open reading frame (ORF) had a homology with the gene PKH (U89606). PKH-T was specifically and strongly expressed in the testis. Comparison of the differential expressions of PKH and PKH-T in testes of different develop-mental stages indicated that PKH-T was expressed in the adult testis and spermatozoa, while PKH, in the adult, fetal and aged testes. PKH-T had no expression in the testis of Sertoli cell only and partially spermatogenic arrest patients.Conclusion: PKH-T is a gene highly expressed in adult human testis and spermatozoa. It may play an important role in spermatogenesis and could be related to male infertility.

  11. Gestation under chronic constant light leads to extensive gene expression changes in the fetal rat liver.

    Science.gov (United States)

    Spichiger, Carlos; Torres-Farfan, Claudia; Galdames, Hugo A; Mendez, Natalia; Alonso-Vazquez, Pamela; Richter, Hans G

    2015-12-01

    Recent reports account for altered metabolism in adult offspring from pregnancy subjected to abnormal photoperiod, suggesting fetal programming of liver physiology. To generate a pipeline of subsequent mechanistic experiments addressing strong candidate genes, here we investigated the effects of constant gestational light on the fetal liver transcriptome. At 10 days of gestation, dams were randomized in two groups (n = 7 each): constant light (LL) and normal photoperiod (12 h light/12 h dark; LD). At 18 days of gestation, RNA was isolated from the fetal liver and subjected to DNA microarray (Affymetrix platform for 28,000 genes). Selected differential mRNAs were validated by quantitative PCR (qPCR), while integrated transcriptional changes were analyzed with Ingenuity Pathway Analysis and other bioinformatics tools. Comparison of LL relative to LD fetal liver led to the following findings. Significant differential expression was found for 3,431 transcripts (1,960 upregulated and 1,471 downregulated), with 393 of them displaying ≥ 1.5-fold change. We validated 27 selected transcripts by qPCR, which displayed fold-change values highly correlated with microarray (r(2) = 0.91). Different markers of nonalcoholic fatty liver disease were either upregulated (e.g., Ndn and Pnpla3) or downregulated (e.g., Gnmt, Bhmt1/2, Sult1a1, Mpo, and Mat1a). Diverse pathways were altered, including hematopoiesis, coagulation cascade, complement system, and carbohydrate and lipid metabolism. The microRNAs 7a-1, 431, 146a, and 153 were upregulated, while the abundant hepatic miRNA 122 was downregulated. Constant gestational light induced extensive modification of the fetal liver transcriptome. A number of differentially expressed transcripts belong to fundamental functional pathways, potentially contributing to long-term liver disease.

  12. Establishing the “Biological Relevance” of Dipentyl Phthalate Reductions in Fetal Rat Testosterone Production and Plasma and Testis Testosterone Levels

    Data.gov (United States)

    U.S. Environmental Protection Agency — metadata sheet, data sheet for each table and figure in the published manuscript. This dataset is associated with the following publication: Gray , E., J. Furr , K....

  13. Effectiveness of xenotransplantation of human fetal hepatocytes in spleen of rats with acute liver failure induced by CCL4

    Directory of Open Access Journals (Sweden)

    Abdukhakim Khadjibaev

    2013-04-01

    Full Text Available Human’s fetal hepatocytes (HFH were intrasplenic transplanted white non-pedigree rats with acute liver failure (ALF challenged by single per oral administration of hepatotropic toxin diluted in oil ССl4 at a dose 10 ml/kg (volumetric correlation 1:1 (10 mL/kg body weight as a 1:1 mixture of CCl4 and mineral oil. Transplantation had positive effect on all biochemical blood parameters of the studying animals. Morphologic study showed that reparative-restorative processes were arising in hepatic parenchyma after administration of HFH into splenic pulp of rats with model of ALF on days 14-21. Substantial and main factor in restoration of parenchyma was restoration of micro topographic interrelations in acinus as well as polyploidy of hepatic cells expressed in increase of hepatocytes’ nuclei sizes and hypertrophy of cells themselves. It is an indirect confirmation of engraftment of HFH in liver of rats with model of ALF.

  14. Hanging drop cultures of human testis and testis cancer samples

    DEFF Research Database (Denmark)

    Jørgensen, Anne; Young, J; Nielsen, J E

    2014-01-01

    limited by the lack of experimental models. The aim of this study was to establish an experimental tissue culture model to maintain normal and malignant germ cells within their niche and allow investigation of treatment effects. METHODS: Human testis and testis cancer specimens from orchidectomies were...

  15. Biosynthesis of the D2 cell adhesion molecule: pulse-chase studies in cultured fetal rat neuronal cells

    DEFF Research Database (Denmark)

    Lyles, J M; Norrild, B; Bock, E

    1984-01-01

    D2 is a membrane glycoprotein that is believed to function as a cell adhesion molecule (CAM) in neural cells. We have examined its biosynthesis in cultured fetal rat brain neurones. We found D2-CAM to be synthesized initially as two polypeptides: Mr 186,000 (A) and Mr 136,000 (B). With increasing...... chase times the Mr of both molecules increased to 187,000-201,000 (A) and 137,000-158,000 (B). These were similar to the sizes of D2-CAM labeled with [14C]glucosamine, [3H]fucose and [14C]mannosamine, indicating that the higher Mr species are glycoproteins. In the presence of tunicamycin, which...... pulse or chase times, showing that these molecules are not interconverted. Thus, our data indicate that the neuronal D2-CAM glycoproteins are derived from two mRNAs....

  16. Autoradiographic localization of target cells for 1. cap alpha. , 25-dihydroxyvitamin D/sub 3/ in bones from fetal rats

    Energy Technology Data Exchange (ETDEWEB)

    Narbaitz, R.; Stumpf, W.E.; Sar, M.; Huang, S.; DeLuca, H.F.

    1983-01-01

    Thaw-mount autoradiographic studies after injection of /sup 3/H-1,25-D/sub 3/ were conducted on 18- and 20-day-old rat fetuses. In maxillary bones, ribs, and tibia, nuclear concentration of radioactivity was found in osteoprogenitor cells and osteoblasts. Osteocytes and chondrocytes in epiphyseal plates were either unlabeled or weakly labeled. In competition experiments, nuclear concentration of radioactivity was blocked by the injection of a high dose of nonradioactive 1,25-D/sub 3/ prior to the administration of the labeled hormone, but not by a similar dose of nonradioactive 25-D/sub 3/. The results are interpreted as indicating that osteoprogenitor cells and osteoblasts are target cells for the direct action of 1,25-D/sub 3/ on fetal bone.

  17. Effects of an overload of animal protein on the rat: brain DNA alterations and tissue morphological modifications during fetal and post-natal stage.

    Science.gov (United States)

    Greco, A M; Sticchi, R; Boschi, G; Vetrani, A; Salvatore, G

    1985-01-01

    On account of many literature reports about the definite correlation between high animal protein intake and cardiovascular diseases, we have studied the effect of a hyperproteic purified diet (casein 40%, lactalbumin 20%) on fetal and post-natal (not further than 40th day) stage of the rat, when cell subdivision process is faster and therefore damage by nutritional imbalance is certainly more serious. Litters of rats were grouped according to mother's (either hyperproteic or common basic) and rat's (after lactation) diet. Brain DNA and histology of various organs were studied. Hyperproteic diet during fetal stage and lactation would inhibit brain cell subdivision since overall content of brain DNA would be decreased on autoptic finding. Structural changes were also shown in liver, heart, kidney and adrenal cortex, especially when hyperproteic diet was continued even after lactation.

  18. Co-transplantation of GDNF-overexpressing neural stem cells and fetal dopaminergic neurons mitigates motor symptoms in a rat model of Parkinson's disease.

    Science.gov (United States)

    Deng, Xingli; Liang, Yuanxin; Lu, Hua; Yang, Zhiyong; Liu, Ru'en; Wang, Jinkun; Song, Xiaobin; Long, Jiang; Li, Yu; Lei, Deqiang; Feng, Zhongtang

    2013-01-01

    Striatal transplantation of dopaminergic (DA) neurons or neural stem cells (NSCs) has been reported to improve the symptoms of Parkinson's disease (PD), but the low rate of cell survival, differentiation, and integration in the host brain limits the therapeutic efficacy. We investigated the therapeutic effects of intracranial co-transplantation of mesencephalic NSCs stably overexpressing human glial-derived neurotrophic factor (GDNF-mNSCs) together with fetal DA neurons in the 6-OHDA rat model of PD. Striatal injection of mNSCs labeled by the contrast enhancer superparamagnetic iron oxide (SPIO) resulted in a hypointense signal in the striatum on T2-weighted magnetic resonance images that lasted for at least 8 weeks post-injection, confirming the long-term survival of injected stem cells in vivo. Co-transplantation of GDNF-mNSCs with fetal DA neurons significantly reduced apomorphine-induced rotation, a behavioral endophenotype of PD, compared to sham-treated controls, rats injected with mNSCs expressing empty vector (control mNSCs) plus fetal DA neurons, or rats injected separately with either control mNSCs, GDNF-mNSCs, or fetal DA neurons. In addition, survival and differentiation of mNSCs into DA neurons was significantly greater following co-transplantation of GDNF-mNSCs plus fetal DA neurons compared to the other treatment groups as indicated by the greater number of cell expressing both the mNSCs lineage tracer enhanced green fluorescent protein (eGFP) and the DA neuron marker tyrosine hydroxylase. The success of cell-based therapies for PD may be greatly improved by co-transplantation of fetal DA neurons with mNSCs genetically modified to overexpress trophic factors such as GDNF that support differentiation into DA cells and their survival in vivo.

  19. Co-transplantation of GDNF-overexpressing neural stem cells and fetal dopaminergic neurons mitigates motor symptoms in a rat model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Xingli Deng

    Full Text Available Striatal transplantation of dopaminergic (DA neurons or neural stem cells (NSCs has been reported to improve the symptoms of Parkinson's disease (PD, but the low rate of cell survival, differentiation, and integration in the host brain limits the therapeutic efficacy. We investigated the therapeutic effects of intracranial co-transplantation of mesencephalic NSCs stably overexpressing human glial-derived neurotrophic factor (GDNF-mNSCs together with fetal DA neurons in the 6-OHDA rat model of PD. Striatal injection of mNSCs labeled by the contrast enhancer superparamagnetic iron oxide (SPIO resulted in a hypointense signal in the striatum on T2-weighted magnetic resonance images that lasted for at least 8 weeks post-injection, confirming the long-term survival of injected stem cells in vivo. Co-transplantation of GDNF-mNSCs with fetal DA neurons significantly reduced apomorphine-induced rotation, a behavioral endophenotype of PD, compared to sham-treated controls, rats injected with mNSCs expressing empty vector (control mNSCs plus fetal DA neurons, or rats injected separately with either control mNSCs, GDNF-mNSCs, or fetal DA neurons. In addition, survival and differentiation of mNSCs into DA neurons was significantly greater following co-transplantation of GDNF-mNSCs plus fetal DA neurons compared to the other treatment groups as indicated by the greater number of cell expressing both the mNSCs lineage tracer enhanced green fluorescent protein (eGFP and the DA neuron marker tyrosine hydroxylase. The success of cell-based therapies for PD may be greatly improved by co-transplantation of fetal DA neurons with mNSCs genetically modified to overexpress trophic factors such as GDNF that support differentiation into DA cells and their survival in vivo.

  20. Co-Transplantation of GDNF-Overexpressing Neural Stem Cells and Fetal Dopaminergic Neurons Mitigates Motor Symptoms in a Rat Model of Parkinson’s Disease

    Science.gov (United States)

    Lu, Hua; Yang, Zhiyong; Liu, Ru’en; Wang, Jinkun; Song, Xiaobin; Long, Jiang; Li, Yu; Lei, Deqiang; Feng, Zhongtang

    2013-01-01

    Striatal transplantation of dopaminergic (DA) neurons or neural stem cells (NSCs) has been reported to improve the symptoms of Parkinson’s disease (PD), but the low rate of cell survival, differentiation, and integration in the host brain limits the therapeutic efficacy. We investigated the therapeutic effects of intracranial co-transplantation of mesencephalic NSCs stably overexpressing human glial-derived neurotrophic factor (GDNF-mNSCs) together with fetal DA neurons in the 6-OHDA rat model of PD. Striatal injection of mNSCs labeled by the contrast enhancer superparamagnetic iron oxide (SPIO) resulted in a hypointense signal in the striatum on T2-weighted magnetic resonance images that lasted for at least 8 weeks post-injection, confirming the long-term survival of injected stem cells in vivo. Co-transplantation of GDNF-mNSCs with fetal DA neurons significantly reduced apomorphine-induced rotation, a behavioral endophenotype of PD, compared to sham-treated controls, rats injected with mNSCs expressing empty vector (control mNSCs) plus fetal DA neurons, or rats injected separately with either control mNSCs, GDNF-mNSCs, or fetal DA neurons. In addition, survival and differentiation of mNSCs into DA neurons was significantly greater following co-transplantation of GDNF-mNSCs plus fetal DA neurons compared to the other treatment groups as indicated by the greater number of cell expressing both the mNSCs lineage tracer enhanced green fluorescent protein (eGFP) and the DA neuron marker tyrosine hydroxylase. The success of cell-based therapies for PD may be greatly improved by co-transplantation of fetal DA neurons with mNSCs genetically modified to overexpress trophic factors such as GDNF that support differentiation into DA cells and their survival in vivo. PMID:24312503

  1. Region-specific growth effects in the developing rat prostate following fetal exposure to estrogenic ultraviolet filters.

    Science.gov (United States)

    Hofkamp, Luke; Bradley, Sarahann; Tresguerres, Jesus; Lichtensteiger, Walter; Schlumpf, Margret; Timms, Barry

    2008-07-01

    Exposure to environmental endocrine disruptors is a potential risk factor for humans. Many of these chemicals have been shown to exhibit disruption of normal cellular and developmental processes in animal models. Ultraviolet (UV) filters used as sunscreens in cosmetics have previously been shown to exhibit estrogenic activity in in vitro and in vivo assays. We examined the effects of two UV filters, 4-methylbenzylidene camphor (4-MBC) and 3-benzylidene camphor (3-BC), in the developing prostate of the fetal rat. Pregnant Long Evans rats were fed diets containing doses of 4-MBC and 3-BC that resulted in average daily intakes of these chemicals corresponding to the lowest observed adverse effects level (LOAEL) and the no observed adverse effects level (NOAEL) doses in prior developmental toxicity studies. Using digital photographs of serial sections from postnatal day 1 animals, we identified, contoured, and aligned the epithelial ducts from specific regions of the developing prostate, plus the accessory sex glands and calculated the total volume for each region from three-dimensional, surface-rendered models. Fetal exposure to 4-MBC (7.0 mg/kg body weight/day) resulted in a significant increase (p < 0.05) in tissue volume in the prostate and accessory sex glands. Treated males exhibited a 62% increase in the number of ducts in the caudal dorsal prostate. Increased distal branching morphogenesis appears to be a consequence of exposure in the ventral region, resulting in a 106% increase in ductal volume. 4-MBC exposure during development of the male reproductive accessory sex glands exhibited classical growth effects associated with estrogenic endocrine disruptors. The different regional responses suggest that the two developmental processes of ductal outgrowth and branching morphogenesis are affected independently by exposure to the environmental chemicals.

  2. Late appearance of a type I alveolar epithelial cell marker during fetal rat lung development.

    Science.gov (United States)

    Danto, S I; Zabski, S M; Crandall, E D

    1994-10-01

    Recent studies in fetal lung using immunological and molecular probes have revealed type I and type II cell phenotypic markers in primordial lung epithelial cells prior to the morphogenesis of these cell types. We have recently developed monoclonal antibodies specific for adult type I cells. To evaluate further the temporal appearance of the type I cell phenotype during alveolar epithelial cell ontogeny, we analyzed fetal lung development using one of our monoclonal antibodies (mAb VIII B2). The epitope recognized by mAb VIII B2 first appears in the canalicular stage of fetal lung development, at approx. embryonic day 19 (E19), in occasional, faintly stained tubules. Staining with this type I cell probe becomes more intense and more widespread with increasing gestational age, during which time the pattern of staining changes. Initially, all cells of the distal epithelial tubules are uniformly labelled along their apical and basolateral surfaces. As morphological differentiation of the alveolar epithelium proceeds, type I cell immunoreactivity appears to become restricted to the apical surface of the primitive type I cells in a pattern approaching that seen in the mature lung. We concurrently analyzed developing fetal lung with an antiserum to surfactant apoprotein-A (alpha-SP-A). Consistent with the findings of others, labeling of SP-A was first detectable in scattered cuboidal cells at E18. Careful examination of the double-labeled specimens suggested that some cells were reactive with both the VIII B2 and SP-A antibodies, particularly at E20. Confocal microscopic analysis of such sections from E20 lung confirmed this impression. Three populations of cells were detected: cells labeled only with alpha-SP-A, cells labeled only with mAb VIII B2, and a smaller subset of cells labeled by both.(ABSTRACT TRUNCATED AT 250 WORDS)

  3. Undescended testis in Spigelian hernia

    Directory of Open Access Journals (Sweden)

    Ravi Kumar V

    2007-01-01

    Full Text Available Spigelian hernias are uncommon in children. We report a 3-year-old boy with right spigelian hernia and right undescended testis. The hernial sac contained the testis, which is a rare presentation. The repair of the large defect with a prosthetic mesh and a concomitant orchidopexy were performed uneventfully.

  4. The ontogeny of scarless healing II: EGF and PDGF-B gene expression in fetal rat skin and fibroblasts as a function of gestational age.

    Science.gov (United States)

    Peled, Z M; Rhee, S J; Hsu, M; Chang, J; Krummel, T M; Longaker, M T

    2001-10-01

    Twenty years ago, surgeons noted the ability of early-gestation fetal skin to heal in a scarless manner. Since that time, numerous investigators have attempted to elucidate the mechanisms behind this phenomenon. As a result of this effort, it is now well established that many animals undergo a transition late in development from scarless cutaneous healing to a scar-forming, adultlike phenotype. The authors have been interested in the role played by cytokines known to be involved in the adult wound-healing process and how they relate to scarless repair. They therefore asked the following question: Are genes for epidermal growth factor (EGF) and platelet-derived growth factor-B (PDGF-B) expressed differentially as a function of gestational age in fetal rat skin and dermal fibroblasts? To answer this question, skin from fetal Sprague-Dawley rats (N = 56) at time points that represented both the scarless and scar-forming periods of rat gestation was harvested. In addition, fibroblasts derived from fetal rat skin were cultured in vitro at similar times. These cells were expanded in culture and, when confluent, total ribonucleic acid from both fibroblasts and whole skin was extracted and subjected to Northern blot analysis with probes for EGF and PDGF-B. Results demonstrated that neither EGF nor PDGF-B gene expression changed markedly as a function of gestational age in fetal fibroblasts alone. In whole skin, however, both EGF and PDGF-B demonstrated a marked decrease in gene expression with increasing gestational age. Furthermore, the most striking decrease in gene expression for both cytokines came between 16 and 18 days of gestation-the transition point between scarless and scar-forming repair in the fetal rat. These data suggest that EGF and PDGF may play a role in the mechanism of scarless cutaneous repair. Moreover, it appears that fetal fibroblasts are not the cell type responsible for this differential gene expression. These results raise questions about the

  5. Viabilidade de células do sistema nervoso central fetal no tratamento da lesão medular em ratos Viability of fetal central nervous system cells in the treatment of spinal cord injury in rats

    Directory of Open Access Journals (Sweden)

    Alexandre Fogaça Cristante

    2010-01-01

    Full Text Available OBJETIVOS: Propor um modelo experimental de transplante de células do sistema nervoso fetal de ratos Wistar para o sítio de lesão medular de ratos adultos que permitisse sua sobrevivência e integração para possibilitar protocolos de pesquisa que identificarão outros fatores de regeneração e recuperação funcional pós trauma raquimedular. MÉTODOS: Vinte ratos adultos foram submetidos a laminectomia, e lesão de 5mm de hemimedula realizada com auxílio de microscópio óptico. Quinze deste ratos tiveram seu sítio de lesão medular transplantado com células do sistema nervoso central de fetos de rato; os ratos foram monitorados por 2 dias e tiveram sua coluna vertebral extraída para análise histológica. RESULTADOS: Evidenciou-se que em 60% dos casos as células transplantadas permaneciam viáveis no sítio da lesão e que a reação inflamatória no grupo transplantado era sempre maior que no grupo controle. CONCLUSÃO: O presente trabalho demonstrou a possibilidade de contar com o modelo de pesquisa para transplante de células fetais que permanecem viáveis 2 dias após seu implante.OBJECTIVE: To propose an experimental model for transplantation of fetal cells from the nervous system of Wistar rats to the site of spinal cord injury in adult rats, to enable their survival and integration for research protocols that identify other factors of regeneration and functional recovery following spinal cord trauma. METHODS: Twenty adult rats were submitted to laminectomy and a 5mm incision was made, using an optical microscope, In fifteen of these rats, the site of the spinal cord lesion was transplanted with cells from the fetal rat central nervous system; the rats were monitored for two days, then the spinal cord was removed for histological analysis. RESULTS: In 60% of cases, the transplanted cells remained viable in the site of the lesion; the inflammatory response in the transplanted group was always greater than in the control group

  6. The Study of Fetal Rat Model of Intra-Amniotic Isoproterenol Injection Induced Heart Dysfunction and Phenotypic Switch of Contractile Proteins

    Directory of Open Access Journals (Sweden)

    Yifei Li

    2014-01-01

    Full Text Available To establish a reliable isoproterenol induced heart dysfunction fetal rat model and understand the switches of contractile proteins, 45 pregnant rats were divided into 15 mg/kg-once, 15 mg/kg-twice, sham-operated once, sham-operated twice, and control groups. And 18 adult rats were divided into isoproterenol-treated and control groups. H&E staining, Masson staining, and transmission electron microscope were performed. Apoptotic rate assessed by TUNEL analysis and expressions of ANP, BNP, MMP-2, and CTGF of hearts were measured. Intra-amniotic injections of isoproterenol were supplied on E14.5 and E15.5 for fetuses and 7-day continuous intraperitoneal injections were performed for adults. Then echocardiography was performed with M-mode view assessment on E18.5 and 6 weeks later, respectively. Isoproterenol twice treated fetuses exhibited significant changes in histological evaluation, and mitochondrial damages were significantly severe with increased apoptotic rate. ANP and BNP increased and that of MMP-2 increased in isoproterenol twice treated group compared to control group, without CTGF. The isoforms transition of troponin I and myosin heavy chain of fetal heart dysfunction were opposite to adult procedure. The administration of intra-amniotic isoproterenol to fetal rats could induce heart dysfunction and the regulation of contractile proteins of fetuses was different from adult procedure.

  7. Convenient and efficient enrichment of the CD133+ liver cells from rat fetal liver as a source of liver stem/progenitor cells.

    Science.gov (United States)

    Liu, Weihui; You, Nan; Dou, Kefeng

    2012-01-01

    Although stem cells are commonly isolated by fluorescence-activated cell sorting or magnetic affinity cell sorting, they are very expensive, and they need known markers. However, there is no specific marker for liver stem/progenitor cells (LSPCs). Here, we describe a convenient and efficient method (three-step method) to enrich LSPCs. The fetal liver cells (FLCs) were firstly enriched by Percoll discontinuous gradient centrifugation from the rat fetal liver. Then the FLCs in culture were purified to be homogeneous in size by differential trypsinization and differential adherence. Finally, fetal liver stem/progenitor cells (FLSPCs) were enriched from purified FLCs by Percoll continuous gradient centrifugation. Flow cytometric analysis combining with marker CD133 was used to detect the purity of FLSPCs and evaluate the isolating effects of the three-step method.

  8. Possible promotion of neuronal differentiation in fetal rat brain neural progenitor cells after sustained exposure to static magnetism.

    Science.gov (United States)

    Nakamichi, Noritaka; Ishioka, Yukichi; Hirai, Takao; Ozawa, Shusuke; Tachibana, Masaki; Nakamura, Nobuhiro; Takarada, Takeshi; Yoneda, Yukio

    2009-08-15

    We have previously shown significant potentiation of Ca(2+) influx mediated by N-methyl-D-aspartate receptors, along with decreased microtubules-associated protein-2 (MAP2) expression, in hippocampal neurons cultured under static magnetism without cell death. In this study, we investigated the effects of static magnetism on the functionality of neural progenitor cells endowed to proliferate for self-replication and differentiate into neuronal, astroglial, and oligodendroglial lineages. Neural progenitor cells were isolated from embryonic rat neocortex and hippocampus, followed by culture under static magnetism at 100 mT and subsequent determination of the number of cells immunoreactive for a marker protein of particular progeny lineages. Static magnetism not only significantly decreased proliferation of neural progenitor cells without affecting cell viability, but also promoted differentiation into cells immunoreactive for MAP2 with a concomitant decrease in that for an astroglial marker, irrespective of the presence of differentiation inducers. In neural progenitors cultured under static magnetism, a significant increase was seen in mRNA expression of several activator-type proneural genes, such as Mash1, Math1, and Math3, together with decreased mRNA expression of the repressor type Hes5. These results suggest that sustained static magnetism could suppress proliferation for self-renewal and facilitate differentiation into neurons through promoted expression of activator-type proneural genes by progenitor cells in fetal rat brain.

  9. Effect of Morus nigra aqueous extract treatment on the maternal-fetal outcome, oxidative stress status and lipid profile of streptozotocin-induced diabetic rats.

    Science.gov (United States)

    Volpato, G T; Calderon, I M P; Sinzato, S; Campos, K E; Rudge, M V C; Damasceno, D C

    2011-12-08

    Morus nigra, commonly known as black mulberry, is widely used in Brazilian folk medicine for the diabetes treatment. To evaluate the effect of Morus nigra aqueous extract treatment on maternal lipid and oxidative stress profile, reproductive outcomes, and also fetal anomaly incidence from diabetic and non-diabetic rats. Diabetes was induced by streptozotocin (40 mg/kg) in virgin female Wistar rats. Morus nigra leaf aqueous extract (400 mg/kg) was administered from day 0 to 20 of pregnancy. At day 21 of pregnancy, all rats were anesthetized and killed to obtain blood samples and maternal-fetal data. After treatment with Morus nigra extract, non-diabetic and diabetic rats presented no glycemic changes. Fetuses from diabetic dams, regardless of Morus nigra treatment, were small for pregnancy age. In diabetic dams, plant treatment caused reduced MDA, cholesterol, triglycerides and VLDL levels, and decreased placental index and weight as compared to diabetic group. The fetuses from diabetic rats treated with Morus nigra extract had lower frequency of skeletal and visceral anomalies as compared to diabetic group. Thus, Morus nigra leaf aqueous extract failed to control hyperglycemia in diabetic rats. However, Morus nigra treatment had antioxidant effect, contributing to reduce incidence of internal anomalies in offspring from diabetic dams. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  10. Transitional change in rat fetal cell proliferation in response to ghrelin and des-acyl ghrelin during the last stage of pregnancy

    Energy Technology Data Exchange (ETDEWEB)

    Inoue, Yoshiyuki; Nakahara, Keiko [Department of Veterinary Physiology, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192 (Japan); Kangawa, Kenji [Department of Biochemistry, National Cardiovascular Center Research Institute, Fujishirodai 5-7-1, Suita, Osaka 565-8565 (Japan); Murakami, Noboru, E-mail: a0d201u@cc.miyazaki-u.ac.jp [Department of Veterinary Physiology, Faculty of Agriculture, University of Miyazaki, Miyazaki 889-2192 (Japan)

    2010-03-12

    Expression of mRNA for the ghrelin receptor, GHS-R1a, was detected in various peripheral and central tissues of fetal rats, including skin, bone, heart, liver, gut, brain and spinal cord, on embryonic day (ED)15 and ED17. However, its expression in skin, bone, heart and liver, but not in gut, brain and spinal cord, became relatively weak on ED19 and disappeared after birth (ND2). Ghrelin and des-acyl ghrelin facilitated the proliferation of cultured fetal (ED17, 19), but not neonatal (ND2), skin cells. On the other hand, with regard to cells from the spinal cord and hypothalamus, the proliferative effect of ghrelin continued after birth, whereas the effect of des-acyl ghrelin on neurogenesis in these tissues was lost at the ED19 fetal and ND2 neonatal stages. Immunohistochemistry revealed that the cells in the hypothalamus induced to proliferate by ghrelin at the ND2 stage were positive for nestin and glial fibrillary acidic protein. These results suggest that in the period immediately prior to, and after birth, rat fetal cells showing proliferation in response to ghrelin and des-acyl ghrelin are at a transitional stage characterized by alteration of the expression of GHS-R1a and an undefined des-acyl ghrelin receptor, their responsiveness varying among different tissues.

  11. Influence of recipient gender on intrasplenic fetal liver tissue transplants in rats: cytochrome P450-mediated monooxygenase functions.

    Science.gov (United States)

    Lupp, Amelie; Hugenschmidt, Sabine; Rost, Michael; Müller, Dieter

    2004-05-01

    Rat livers display a sex-specific cytochrome P450 (P450) isoforms expression pattern with consecutive differences in P450-mediated monooxygenase activities, which have been shown to be due to a differential profile of growth hormone (GH) secretion. Parallel to previous investigations on P450 isoforms expression, the aim of the present study was to elucidate the influence of recipient gender on P450-mediated monooxygenase activities in intrasplenic liver tissue transplants in comparison to orthotopic liver. Fetal liver tissue suspensions of mixed gender were transplanted into the spleen of adult male or female syngenic recipients. Four months after grafting transplant-recipients and age-matched controls were treated with beta-naphthoflavone (BNF), phenobarbital (PB), dexamethasone (DEX) or the vehicles and sacrificed 24 or 48 h thereafter. P450-dependent monooxygenase activities were assessed by a series of model reactions for different P450 subtypes in liver and spleen 9000 g supernatants. In spleens of male and female control rats only very low monooxygenase activities were detectable, whereas with most model reactions distinct activities were observed in transplant-containing organs. Livers and transplant-containing spleens from male rats displayed higher basal ethoxycoumarin O-deethylase and testosterone 2alpha-, 2beta-, 6beta-, 14alpha-, 15alpha-, 15beta-, 16alpha-, 16beta- and 17-hydroxylase activities than those from females. On the other hand, like the respective livers, spleens from female transplant-recipients demonstrated more pronounced p-nitrophenol- and testosterone 6alpha- and 7alpha-hydroxylase activities than those from male hosts. With nearly all model reactions gender-specific differences in inducibility by BNF, PB or DEX could be demonstrated in livers as well as in transplant-containing spleens. These results further confirm that the P450 system of intrasplenic liver tissue transplants and the respective orthotopic livers is similarly influenced

  12. Fetal Circulation

    Science.gov (United States)

    ... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More Fetal Circulation Updated:Oct 18,2016 click to enlarge The ... fetal heart. These two bypass pathways in the fetal circulation make it possible for most fetuses to survive ...

  13. Developmental changes of cytochrome P450 dependent monooxygenase functions after transplantation of fetal liver tissue suspension into spleens of adult syngenic rats.

    Science.gov (United States)

    Lupp, A; Trautmann, A K; Krausse, T; Klinger, W

    1998-06-01

    Fetal liver tissue suspensions were transplanted into the spleens of adult male syngenic Fisher 344 inbred rats. Animals were sacrificed at 3 days, 1, 2, 4 weeks, and 2, 4 and 6 months after transplantation and cytochrome P450 (P450) dependent monooxygenase functions in spleen and liver 9000 g supernatants were assessed by measuring three model reactions for different P450 subtypes: ethoxyresorufin O-deethylation (EROD; mainly 1A), ethoxycoumarin O-deethylation (ECOD; predominantly 1A, 2A, 2B) and ethylmorphine N-demethylation (END; mainly 3A). Values of transplant recipients were compared to those of sham operated and age matched control rats. Spleen weights were significantly higher in transplanted rats, compared to controls or sham operated animals, but there was no influence of the transplants within the spleens on liver weights. With fetal livers at the 21st day of gestation, the day of transplantation, a weak EROD and ECOD, but no END activity was seen. Spleens of controls or sham operated animals displayed nearly no P450 mediated monooxygenase functions. In the explant containing spleens a significant and increasing EROD activity was found from 4 weeks after surgery on and an ECOD activity already 2 weeks after transplantation. END was only slightly enhanced at 6 months after surgery. The livers of all three groups of rats displayed normal EROD, ECOD and END activities. Transplantation of fetal liver tissue suspensions into the spleens did not influence the P450 dependent monooxygenase functions within the livers of the animals. From these results it can be concluded that intrasplenically transplanted liver cells originating from syngenic fetal liver tissue suspensions proliferate and differentiate within the host organs. They display P450 dependent monooxygenase functions with some developmental changes during the observed time period of 6 months.

  14. [The relationship between the effects of MTA on mRNA expression of four iconic proteins in cells of fetal rat skull and cell culture environment].

    Science.gov (United States)

    Zheng, Jun-Yuan; He, Li; Hu, Tu-qiang

    2016-02-01

    To discuss the influence of MTA on mRNA expression of Cbfa1, ALP, Col-Ⅰand BGP which are 4 kinds of iconic protein in cells of fetal rats skull, and explore its influence on cell culture environment and association of changes of calcium, phosphorus. Cells were obtained by 2 kinds of mixed enzymatic digestion for 3 steps from gestation fetal rat calvarial bone. The expression of Cbfa1mRNA, ALPmRNA, Col-1mRNA, BGP mRNA and extracellular calcium were detected. Phosphorus (P) and calcium concentration of fetal rat skull cells co-cultured with MTA for 3 weeks at different stages of cell differentiation was assessed atomic absorption spectrophotometry. The data was statistically analyzed using SPSS10.0 software package. At the 4th day, P3- content decreased significantly (PMTA group increased most greatly and was 40 times of the control group. At the 14th to 18th day, the Ca2+ and P3- content reduced significantly (PMTA group rised most greatly which was about 7.71 times of the control group. Then Cbfalpha l mRNA in MTA group increased most strongly later which was about 7.38 times of the control group. Col Ⅰ mRNA increased minimally in all time points. The change of P3- content may be the initiating factor when MTA promoted differentiation of fetal rats skull cells in vitro, and Ca2+ could greatly accelerate the process of mineralization when accumulated to a certain extent. At the same time, the expression of ALPmRNA, BGPmRNA, Col Ⅰ mRNA and Cbfalpha lmRNA were regulated accordingly, which is the key to explain osteogenetic mechanism of MTA.

  15. Expression of AFP and Rev-Erb A/Rev-Erb B and N-CoR in fetal rat liver, liver injury and liver regeneration

    OpenAIRE

    Meier, Volker; Tron, Kyrylo; Batusic, Danko; Elmaouhoub, Abderrahim; Ramadori, Giuliano

    2006-01-01

    Background Alpha-fetoprotein (AFP) expression can resume in the adult liver under pathophysiological conditions. Orphan nuclear receptors were supposed to regulate AFP gene expression, in vitro. We were interested to study the expression of AFP and orphan nuclear receptors, in vivo. Results The expression of AFP gene and orphan nuclear receptors in the liver was examined in different rat models: (a) fetal liver (b) liver regeneration [partial hepatectomy (PH) with and without 2-acetyl-aminofl...

  16. Effect of nebivolol treatment during pregnancy on the intrauterine fetal growth, mortality and pup postnatal development in the l-NAME-induced hypertensive rats.

    Science.gov (United States)

    Altoama, Kassem; Mallem, Mohamed Yassine; Thorin, Chantal; Betti, Eric; Desfontis, Jean-Claude

    2016-11-15

    The present study was carried out to evaluate the effect of nebivolol vs. bisoprolol treatment on the intrauterine fetal growth, mortality and postnatal development in N(ω)-Nitro-l-arginine methyl ester hydrochloride (l-NAME)-induced hypertensive rats. Hypertension was induced in normotensive pregnant Wistar rats by daily administration of l-NAME (100mg/kg/day, in the drinking water) for the period of pregnancy. After 9 days of l-NAME treatment, rats with systolic and diastolic blood pressure (SBP and DBP) more than 140/90mmHg were considered hypertensive. Then, some of them were treated from day 11 to day 18 of pregnancy with nebivolol (8mg/kg/day) or bisoprolol (10mg/kg/day) via oral gavage. SBP, DBP and heart rate (HR) were re-evaluated by tail cuff method on day 19 of pregnancy and morphometrical or histological studies were performed on day 20. In addition, the mortality and postnatal development of newborn pups were assessed in all groups. The l-NAME administration during pregnancy induced an increase in SBP and DBP while HR did not change. Nebivolol or bisoprolol treatment completely prevented the elevation of SBP and DBP induced by l-NAME with a reduction in HR in pregnant and non-pregnant rats. The intra-uterine fetal growth and the postnatal development of newborn rats in nebivolol-treated hypertensive group were significantly lower vs. control and higher vs. bisoprolol-treated group with a higher mortality in the both types of treatments vs. control rats. The nebivolol and bisoprolol administration produce adverse effects on fetal growth and postnatal development, that limits their therapeutic use in females during pregnancy.

  17. The consequence of fetal ethanol exposure and adolescent odor re-exposure on the response to ethanol odor in adolescent and adult rats

    Directory of Open Access Journals (Sweden)

    Molina Juan C

    2009-01-01

    Full Text Available Abstract Background An epidemiologic predictive relationship exists between fetal ethanol exposure and the likelihood for adolescent use. Further, an inverse relationship exists between the age of first experience and the probability of adult abuse. Whether and how the combined effects of prenatal and adolescent ethanol experiences contribute to this progressive pattern remains unknown. Fetal ethanol exposure directly changes the odor attributes of ethanol important for both ethanol odor preference behavior and ethanol flavor perception. These effects persist only to adolescence. Here we tested whether adolescent ethanol odor re-exposure: (Experiment 1 augments the fetal effect on the adolescent behavioral response to ethanol odor; and/or (Experiment 2 perpetuates previously observed adolescent behavioral and neurophysiological responses into adulthood. Methods Pregnant rats received either an ethanol or control liquid diet. Progeny (observers experienced ethanol odor in adolescence via social interaction with a peer (demonstrators that received an intragastric infusion of either 1.5 g/kg ethanol or water. Social interactions were scored for the frequency that observers followed their demonstrator. Whole-body plethysmography evaluated the unconditioned behavioral response of observers to ethanol odor in adolescence (P37 or adulthood (P90. The olfactory epithelium of adults was also examined for its neural response to five odorants, including ethanol. Results Experiment 1: Relative to fetal or adolescent exposure alone, adolescent re-exposure enhanced the behavioral response to ethanol odor in P37 animals. Compared to animals with no ethanol experience, rats receiving a single experience (fetal or adolescent show an enhanced, yet equivalent, ethanol odor response. Fetal ethanol experience also increased olfactory-guided following of an intoxicated peer. Experiment 2: Combined exposure yielded persistence of the behavioral effects only in adult

  18. Maternal and fetal toxicity of Wistar rats exposed to herbicide metolachlor

    Directory of Open Access Journals (Sweden)

    Kátia Cristina de Melo Tavares Vieira

    2016-07-01

    Full Text Available Metolachlor is a selective pre-emergent herbicide widely used in agriculture to control weeds. The aim of this study was to evaluate the possible effects of metolachlor on reproductive performance of adult rats, as well as its teratogenic potential when administered during the period of organogenesis. Pregnant adult female rats were allocated into 4 experimental groups (n = 10 group-1, that received 0 (control; 150 (TA; 300 (TB; or 1000 mg kg-1 bw day-1 (TC of metolachlor, by gavage, from the 6th to 15th gestational day (GD. There is reduction in the weight gain of the animals from TB and TC groups compared to the control group. Liver and placenta weights were reduced in TB and TC groups, respectively, while the percentage of post-implantation loss was increased in the TC group. There were no external malformations in either rat of the control or treated groups. However, an increased incidence of skeletal anomalies and visceral anomalies (especially in the urogenital system was observed in TC group. These results demonstrate that exposure of pregnant rats to metolachlor can lead to signs of general toxicity, late embryonic losses and congenital anomalies.

  19. Fetal effects of epidermal growth factor deficiency induced in rats by autoantibodies against epidermal growth factor

    DEFF Research Database (Denmark)

    Raaberg, Lasse; Nexø, Ebba; Jørgensen, P E

    1995-01-01

    , the amount of surfactant protein-A was decreased, suggesting a delayed lung maturation. The offspring of EGF-immunized rats had dry and wrinkled skin. The skin was thin and the hair follicles were immature. This suggests a role for EGF in the growth and development of the skin. The liver/body weight ratio...

  20. Congenital hypothyroidism, as studied in rats. Crucial role of maternal thyroxine but not of 3,5,3'-triiodothyronine in the protection of the fetal brain.

    Science.gov (United States)

    Calvo, R; Obregón, M J; Ruiz de Oña, C; Escobar del Rey, F; Morreale de Escobar, G

    1990-09-01

    To study the protective effects of maternal thyroxine (T4) and 3,5,3'-triiodothyronine (T3) in congenital hypothyroidism, we gave pregnant rats methimazole (MMI), an antithyroid drug that crosses the placenta, and infused them with three different doses of T4 or T3. The concentrations of both T4 and T3 were determined in maternal and fetal plasma and tissues (obtained near term) by specific RIAs. Several thyroid hormone-dependent biological end-points were also measured. MMI treatment resulted in marked fetal T4 and T3 deficiency. Infusion of T4 into the mothers increased both these pools in a dose-dependent fashion. There was a preferential increase of T3 in the fetal brain. Thus, with a T4 dose maintaining maternal euthyroidism, fetal brain T3 reached normal values, although fetal plasma T4 was 40% of normal and plasma TSH was high. The infusion of T3 pool into the mothers increased the total fetal extrathyroidal T3 pool in a dose-dependent fashion. The fetal T4 pools were not increased, however, and this deprived the fetal brain (and possibly the pituitary) of local generation of T3 from T4. As a consequence, fetal brain T3 deficiency was not mitigated even when dams were infused with a toxic dose of T3. The results show that (a) there is a preferential protection of the brain of the hypothyroid fetus from T3 deficiency; (b) maternal T4, but not T3, plays a crucial role in this protection, and (c) any condition which lowers maternal T4 (including treatment with T3) is potentially harmful for the brain of a hypothyroid fetus. Recent confirmation of transplacental passage of T4 in women at term suggests that present results are relevant for human fetuses with impairment of thyroid function. Finding signs of hypothyroidism at birth does not necessarily mean that the brain was unprotected in utero, provided maternal T4 is normal. It is crucial to realize that maintainance of maternal "euthyroidism" is not sufficient, as despite hypothyroxinemia, the mothers may be

  1. Influência da icterícia obstrutiva na capacidade reprodutiva, desenvolvimento fetal e morfologia ovariana em ratas Influence of jaundice in the reproductive capacity, fetal development and ovarian morphology in rats

    Directory of Open Access Journals (Sweden)

    Vivian Resende

    2009-08-01

    Full Text Available OBJETIVO: Estudar a influência da icterícia obstrutiva sobre a capacidade reprodutiva e desenvolvimento fetal em ratas. MÉTODOS: Foram utilizadas 60 ratas sexualmente maduras e sabidamente férteis distribuídas em dois grupos: grupo 1 (n=30- submetidas a ligadura do ducto biliopancreático e grupo 2 (n=30 -controles. A partir do 23? dia pós-operatório, as ratas foram acasaladas e seus ciclos estrais avaliados diariamente por meio de esfregaços vaginais, que permitiram determinar o dia da cópula e a idade gestacional em que foram mortas. Realizou-se estudo histológico dos corpos lúteos nos ovários de todas as ratas e analisou-se macroscopicamente a morfologia externa dos fetos. RESULTADOS: Observou-se que 23 ratas controle (92% e 11 ratas ictéricas (39,3% desenvolveram prenhez (p=0,0002. As 17 ratas com hiperbilirrubinemia e sem prenhez (60,7% apresentaram somente corpos lúteos com aspecto involutivo em seus ovários e sofreram modificações em seus ciclos estrais, permanecendo vários dias em proestro ou estro. As ratas prenhes com hiperbilirrubinemia não apresentaram alterações em seus corpos lúteos, porém os seus fetos eram anormais. CONCLUSÃO: Em presença de hiperbilirrubinemia, a fertilização é viável, a capacidade reprodutiva é muito reduzida, os ciclos estrais tornam-se irregulares, o epitélio vaginal permanece cornificado, os corpos lúteos ovarianos regridem, os corpos lúteos gravídicos não são alterados aumentando progressivamente durante a prenhez e o desenvolvimento fetal é gravemente alterado.OBJECTIVE: To assess the influence of jaundice on the reproductive capacity and fetal development in rats. METHODS: 60 sexually mature rats were divided into two groups: Group 1 (n=30 - submitted to ligature of the biliopancreatic duct and Group 2 (n=30 -control- submitted only to sham operation. 23 days later, the animals were matted with sexually mature males for copulation. Vaginal smears were daily collected

  2. Influência da multimistura na gestação de ratas: pesos materno e fetal e triglicerídeos séricos Multimixture influence on rats gestation: maternal and fetal weights and serum triglycerides

    Directory of Open Access Journals (Sweden)

    Vilma Blondet de Azeredo

    2003-01-01

    Full Text Available O presente estudo visa determinar a influência da multimistura (MM sobre o ganho de peso materno e fetal e sobre a hipertrigliceridemia materna no final do período gestacional. Foram utilizadas ratas Wistar (n= 120, divididas em quatro grupos: a à base da dieta habitual do Estado do Rio de Janeiro (HERJ; b à base da dieta habitual do Estado do Rio de Janeiro adicionada de 2% de MM (HERJ+MM; c à base de caseína (CAS1 com 12% de proteína; d controle caseína (CAS2 com 20% de proteína. Os pesos materno e fetal foram registrados semanalmente nos dias 7, 14 e 21 do experimento. Para a determinação dos triglicerídeos séricos (mg/dL foram usados Kits BioClin (Química Básica-Quibasa, BH. De acordo com os resultados, a complementação da dieta HERJ com 2% de multimistura não aumentou o ganho de peso materno e fetal e não alterou a hipertrigliceridemia fisiológica. Conclui-se que a utilização da multimistura, na proporção usada durante a gestação, não possui nenhum efeito sobre os parâmetros estudados.The objective of this study was to determine the influence of the multimixture (MM on maternal and fetal weight gain and on maternal hypertriglyceridemia at the end of gestational period. Female Wistar rats (n = 120 were divided into four groups: a typical diet of the state of Rio de Janeiro/Brazil (HERJ; b HERJ diet supplemented with 2% of MM (HERJ+MM; c casein diet (CAS1 with 12% of protein; d casein control (CAS2 with 20% of protein. Maternal and fetal weights were weekly registered in the days 7,14 and 21 of the experiment. Serum triglycerides (mg/dL were determined by kits (BioClin. The results demonstrated that the supplementation of the HERJ diet with 2% of MM did not increase maternal and fetal weight gain and did not alter the hypertriglyceridemia. In conclusion, the multimixture utilization during gestation does not affect these studied parameters.

  3. Characterization of Fetal Antigen 1/Delta-Like 1 Homologue Expressing Cells in the Rat Nigrostriatal System

    DEFF Research Database (Denmark)

    Liechti, Rémy; Ducray, Angélique D; Jensen, Pia;

    2015-01-01

    Fetal antigen 1/delta-like 1 homologue (FA1/dlk1) belongs to the epidermal growth factor superfamily and is considered to be a non-canonical ligand for the Notch receptor. Interactions between Notch and its ligands are crucial for the development of various tissues. Moreover, FA1/dlk1 has been su...... adult rats. FA1/dlk1-ir cells were predominantly distributed in the substantia nigra (SN) pars compacta (SNc) and in the ventral tegmental area. Interestingly, the expression of FA1/dlk1 significantly increased in tyrosine hydroxylase (TH)-ir cells during early postnatal development. Co......-localization and tracing studies demonstrated that FA1/dlk1-ir cells in the SNc were nigrostriatal dopaminergic neurons, and unilateral 6-OHDA lesions resulted in loss of both FA1/dlk1-ir and TH-ir cells in the SNc. Surprisingly, increased numbers of FA1/dlk1-ir cells (by 70%) were detected in dopamine-depleted striata...... as compared to unlesioned controls. The higher number of FA1/dlk1-ir cells was likely not due to neurogenesis as colocalization studies for proliferation markers were negative. This suggests that FA1/dlk1 was up-regulated in intrinsic cells in response to the 6-OHDA-mediated loss of FA1/dlk1-expressing SNc...

  4. Testicular development and reproductivity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Bing, Wang; Masahiro, Murakami; Kiyomi, Eguchi-Kasai; Kumie, Nojima; Yi, Shang; Kaoru, Tanaka; Kazuko, Fujita [National Institute of Radiological Sciences, Inage-ku, Chiba (Japan); Coffigny, H. [CEA Fontenay-aux-Roses, Dir. des Sciences du Vivant, 92 (France)

    2006-07-01

    Effects on gonads in prenatal male fetuses, and on the postnatal testicular development and reproductivity of male offspring were studied following exposure of pregnant Wistar rats to either accelerated carbon-ion beans with a Let value of about 13 keV/L]m or neon-ion beams with a Let value of about 30 keV/I Im at a dose range from 0.1 Gy to 2.0 Gy on gestation day 15. Induction of apoptosis in fetal gonocytes was evaluated pathologically in male gonads. Mean number of pups, pre-weaning mortality, and the age for testis descent in offspring were examined. Testis weight and the ratio of it to body weight were measured on postnatal days 30, 60 and 90, respectively. Development of testicular tubules was analyzed histologically. In addition, in the male offspring, the successful mating rates with non-irradiated female rats, the mean number of pups descended, and, the weaning rates of the pups were investigated. The effects of X-rays at 200 kVp estimated for the same biological end points were studied for comparison. For heavy ions, a dose of 2.0 Gy caused 100% pre-weaning mortality. For some endpoints, such as pre-weaning mortality, testis weight, and ratio of testis weight to body weight, significant alteration was observed in offspring prenatally received only 0.1 Gy of accelerated neon ions; while for the most endpoints regarding the effects from carbon ions or X rays, a significant alteration could be observed only when a dose was at 0.5 Gy or more. In this dose range, apoptosis in gonocytes of fetal gonads was significantly induced in a dose-dependent manner with a peak at around 12 to 18 hr after irradiation; in the prenatally irradiated pups, statistical significances for increased prenatal death, delayed accomplishment in testis descent, low testis weight, changed ratios of testis weight to body weight, and increased malformed testicular tubules were recorded. When the dose was at 1.0 Gy or 1.5 Gy, marked decrease in successful mating rates was also observed

  5. Comparison on the Effects of Three Sex Hormones on the Fetal Rat Calvarial Osteoblasts

    Institute of Scientific and Technical Information of China (English)

    CHEN Lulu; ZENG Tianshu; XIA Wenfang; KE Li

    2000-01-01

    17β-estradiol(E2), progesterone (P) and testosterone (T) were investigated for their effects on the proliferation and differentiation of primary rat calvarial osteoblasts in vitro. Rat calvarial osteoblasts were cultured with l0-10 mol/L E2, 10-9-10-6 mol/L P and l0-10 mol/L T for 20days. Cell proliferation was determined by 3H-thymidine incorporation and cell counting. Cell differentiation was examined by measuring alkaline phosphatase (ALP) activity, osteocalcin gene expression and production, bone nodule formation in different periods of culture. Our results showed that no effect of three sex hormones was observed on cell proliferation, but, the responses of cell differentiation to the hormones were more or less different. Among these three hormones used in this study, P appeared to have multi-stimulating effect on cell differentiation. Effect of T seemed not so significant as that of P on cell differentiation. Although ALP activity and osteocalcin production were increased significantly by T, it had slight effect on osteocalcin mRNA and bone nodule formation. Besides, E2 did not demonstrate any effect on cell differentiation. It is concluded that the proliferation of rat calvarial osteoblasts was independent of the presence of sex hormones. However, the differentiation of these cells were stimulated in different levels and to different extent either by P or T. P appeared to be a multi-stimulator on differentiation of such cells.

  6. Fetal Research

    Science.gov (United States)

    Hansen, John T.; Sladek, John R.

    1989-11-01

    This article reviews some of the significant contributions of fetal research and fetal tissue research over the past 20 years. The benefits of fetal research include the development of vaccines, advances in prenatal diagnosis, detection of malformations, assessment of safe and effective medications, and the development of in utero surgical therapies. Fetal tissue research benefits vaccine development, assessment of risk factors and toxicity levels in drug production, development of cell lines, and provides a source of fetal cells for ongoing transplantation trials. Together, fetal research and fetal tissue research offer tremendous potential for the treatment of the fetus, neonate, and adult.

  7. Differential regulation of leucine-rich primary response gene 1 (LRPR1) mRNA expression in rat testis and ovary

    NARCIS (Netherlands)

    K.E. Slegtenhorst-Eegdeman; M. Verhoef-Post (Miriam); M. Parvinen; J.A. Grootegoed (Anton); A.P.N. Themmen (Axel)

    1998-01-01

    textabstractIn immature rat Sertoli cells, leucine-rich primary response gene 1 (LRPR1) represents a follicle stimulating hormone (FSH)-responsive gene; the function of the encoded protein is not yet known. LRPR1 mRNA expression is up-regulated very rapidly and specific

  8. Comparative Study on the Differentiation of Mesenchymal Stem Cells Between Fetal and Postnatal Rat Spinal Cord Niche.

    Science.gov (United States)

    Cao, Songying; Wei, Xiaowei; Li, Hui; Miao, Jianing; Zhao, Guifeng; Wu, Di; Liu, Bo; Zhang, Yi; Gu, Hui; Wang, Lili; Fan, Yang; An, Dong; Yuan, Zhengwei

    2016-01-01

    In a previous study, we established a prenatal surgical approach and transplanted mesenchymal stem cells (MSCs) into the fetal rat spinal column to treat neural tube defects (NTDs). We found that the transplanted MSCs survived and differentiated into neural lineage cells. Various cytokines and extracellular signaling systems in the spinal cord niche play an important role in cell differentiation. In this study, we observed the differentiation of transplanted MSCs in different spinal cord niches and further observed the expression of neurotrophic factors and growth factors in the spinal cord at different developmental stages to explore the mechanism of MSC differentiation in different spinal cord niches. The results showed that transplanted MSCs expressed markers of neural precursor cells (nestin), neurogliocytes (GFAP), and neurons (β-tubulin). The percentages of GFP(+)/nestin(+) double-positive cells in transplanted MSCs in E16, P1, and P21 rats were 18.31%, 12.18%, and 5.06%, respectively. The percentages of GFP(+)/GFAP(+) double-positive cells in E16, P1, and P21 rats were 32.01%, 15.35%, and 12.56%, respectively. The percentages of GFP(+)/β-tubulin(+) double-positive cells in E16, P1, and P21 were 11.76%, 7.62%, and 4.88%, respectively. The differentiation rates of MSCs in embryonic spinal cords were significantly higher than in postnatal spinal cords (p < 0.05). We found that the transplanted MSCs expressed synapsin-1 at different developmental stages. After MSC transplantation, we observed that neurotrophic factor-3 (NT-3), fibroblast growth factor-2 (FGF-2), FGF-8, transforming growth factor-α (TGF-α), vascular endothelial growth factor (VEGF), and platelet-derived growth factor (PDGF) significantly increased in the MSC transplantation group compared with the blank injection group. Furthermore, FGF-2 and VEGF expression were positively correlated with the number of surviving MSCs. In addition, we found that the expression of brain

  9. Influence of recipient gender on cytochrome P450 isoforms expression in intrasplenic fetal liver tissue transplants in rats.

    Science.gov (United States)

    Lupp, Amelie; Hugenschmidt, Sabine; Danz, Manfred; Müller, Dieter

    2003-06-30

    Rat livers display a sex-specific cytochrome P450 (P450) isoforms expression pattern which is regulated by a differential profile of growth hormone (GH) secretion. The aim of the present study was to elucidate whether liver cell transplants at an ectopic site are also subject to this influence. Fetal liver tissue suspensions of mixed gender were transplanted into the spleen of adult male or female syngenic recipients. Four months after grafting transplant recipients and age-matched controls were treated with beta-naphthoflavone (BNF), phenobarbital (PB), dexamethasone (DEX) or the solvents and sacrificed 24 or 48 h thereafter. Livers and intrasplenic transplants were evaluated for the expression of the P450 subtypes 1A1, 2B1, 2E1, 3A2 and 4A1 by means of immunohistochemistry. The livers of both male and female rats displayed nearly no P450 1A1, but a distinct P450 2B1, 2E1, 3A2 and 4A1 expression. Whereas no sex differences were seen in the P450 1A1 expression, the immunostaining for P450 2B1, 3A2 and 4A1 was stronger in males and that for P450 2E1 in females. Similarly, in the intrasplenic liver cell transplants almost no P450 1A1, but a noticeable P450 2B1, 2E1, 3A2 and 4A1 expression was observed. Like in the respective livers, the immunostaining for P450 2B1, 3A2 and 4A1 was stronger in the transplants hosted by male than by female rats, whereas the opposite was the case for the P450 2E1 expression. Both in livers and transplants with some sex-specific differences P450 1A1 and 2E1 expression was induced by BNF, that of P450 2B1 by BNF and PB, and that of P450 3A2 by PB and DEX. These results indicate that the P450 system of ectopically transplanted liver cells is influenced by the gender of the recipient organism like that of the orthotopic livers.

  10. Investigation of the effects of acrylamide applied during pregnancy on fetal brain development in rats and protective role of the vitamin E.

    Science.gov (United States)

    Erdemli, M E; Turkoz, Y; Altinoz, E; Elibol, E; Dogan, Z

    2016-12-01

    A liberal amount of acrylamide (AA) is produced as a result of frying or baking foods in high temperatures, and individuals take certain amounts of AA everyday by consuming these food items. Pregnant women are also exposed to AA originating from food during pregnancy and their fetus are probably affected. The rats were divided into five different groups: control (C), corn oil (CO), vitamin E (Vit E), AA, and Vit E + AA, with eight pregnant rats in each group. On the 20th day of pregnancy, fetuses were removed and brain tissues of fetuses were examined for biochemical and histological changes. AA caused degeneration in neuron structures in fetal brain tissue and caused hemorrhagic damages; dramatically decreased brain-derived neurotrophic factor levels; increased malondialdehyde, total oxidant capacity levels; and decreased reduced glutathione and total antioxidant capacity levels (p E, a neuroprotectant and a powerful antioxidant, suppressed the effects of AA on fetal development and fetal brain tissue damage for the above-mentioned parameters (p E as a protection to minimize the toxic effects of food-oriented AA on fetus development due to the widespread nature of fast-food culture in today's life and the impossibility of protection from AA toxicity.

  11. Experiment K-314: Fetal and neonatal rat bone and joint development following in Utero spaceflight

    Science.gov (United States)

    Sabelman, E. E.; Holton, E. M.; Arnaud, C. D.

    1981-01-01

    Infant rat limb specimens from Soviet and U.S. ground-based studies were examined by radiography, macrophotography, histologic sectioning and staining and scanning electron microscopy. A comparison was conducted between vivarium and flight-type diets suggesting that nutritional obesity may adversely affect pregnancy. Data were obtained on maturation of ossification centers, orientation of collagen fibers in bone, tendon and ligaments, joint surface texture and spatial relationships of bones of the hind limb. Computer reconstructions of the knee and hip show promise as a means of investigating the etiology of congenital hip dislocation.

  12. Expression of c-Fos protein and nitricoxide synthase in neurons of cerebral cortex from fetal rats in hypoxia and protective role of Angelica sinensis

    Institute of Scientific and Technical Information of China (English)

    Hong Yu; Hongxian Zhao; Yuling Wu

    2006-01-01

    BACKGROUND: Both c-Fos protein and nitricoxide synthase (NOS) have been used as general indexes in relative research about neurons, but it is lack of reports that c-Fos protein and NOS are applied synchronously to study the neurons of hypoxic fetal rats in uterus.OBJECTIVE: To study the effect of hypoxia in uterus on the expression of c-Fos protein and NOS in neurons of cerebral cortex from fetal rats and whether Angelica sinensis has the protective effect on these neurons in hypoxia.DESIGN: Randomized control experiment.SETTING: Department of Histology and Embryology, Luzhou Medical College.MATERIALS: Twelve adult female Wistar rats in oestrum and 1 male Wistar rat with bodymass from 220 to 250 g were chosen. Parenteral solution of Angelica sinensis mainly contained angelica sinensis, 10 mL/ampoule, was provided by Department of Agent of the Second Hospital Affiliated to Hubei Medical University (batch number: 01062310).METHODS: This experiment was completed in the Department of Histology and Embryology of Luzhou Medical College from September 2003 to June 2004. ① Twelve adult female Wistar rats in oestrum and 1 male Wistar rat were housed in one rearing cage. Vaginal embolus was performed on conceive female rat at 8:00 am next day.On the 15th conceiving day,all conceiving rats were divided randomly into three groups:control group, hypoxia group and Angelica group with 4 in each group. Rats in hypoxia group and Angelica group were modeled with hypotonic hypoxia in uterus. Angelica group: Rats were injected with 8 mL/kg Angelica sinensis injection through caudal veins before hypoxia.Hypoxia group:Rats were injected with the same volume of saline.Control group:Rats were not modeled and fed with normal way. ② Twenty embryos of rats were chosen randomly from each group and then routinely embedded in paraffin. Paraffin sections were cut from the brain of embryos to anterior fontanelle. Double-label staining was used to detect the expression of nNOS and c-Fos in

  13. Expression and Location of Glucose-regulated Protein 78 in Testis and Epididymis

    Directory of Open Access Journals (Sweden)

    W Wang

    2014-04-01

    Full Text Available Objective: To know the role of glucose-regulated protein 78 (GRP78/BiP/HSPA5 in spermatogenesis and its expression and location in the testis and epididymis. Methods: Immunohistochemistry and Western blot were used to detect GRP78 location and expression in the testis and epididymis. Results: Glucose-regulated protein 78 was observed in spermatocytes, round spermatids and interstitial cells of the testis and in principal cells of the epididymis. Glucose-regulated protein 78 was first detected in the rat testis at postnatal day 14. Thereafter, the protein level increased gradually with age and was maintained at a high and stable state after postnatal day 28. In the rat, GRP78 was expressed in the principal cells but not in clear cells of the epididymis. Conclusion: Glucose-regulated protein 78 participates in the process of spermatogenesis.

  14. Oncogenic cancer/testis antigens

    DEFF Research Database (Denmark)

    Gjerstorff, Morten F; Andersen, Mads H; Ditzel, Henrik J

    2015-01-01

    Recent developments have set the stage for immunotherapy as a supplement to conventional cancer treatment. Consequently, a significant effort is required to further improve efficacy and specificity, particularly the identification of optimal therapeutic targets for clinical testing. Cancer....../testis antigens are immunogenic, highly cancer-specific, and frequently expressed in various types of cancer, which make them promising candidate targets for cancer immunotherapy, including cancer vaccination and adoptive T-cell transfer with chimeric T-cell receptors. Our current understanding of tumor...... immunology and immune escape suggests that targeting oncogenic antigens may be beneficial, meaning that identification of cancer/testis antigens with oncogenic properties is of high priority. Recent work from our lab and others provide evidence that many cancer/testis antigens, in fact, have oncogenic...

  15. Somatostatin and leu-enkephalin in the rat auditory brainstem during fetal and postnatal development.

    Science.gov (United States)

    Kungel, M; Friauf, E

    1995-05-01

    A transient expression of the neuropeptide somatostatin has been described in several brain areas during early ontogeny and several opioid peptides, such as leu-enkephalin, have also been found in the brain at this stage in development. It is therefore believed that somatostatin and leu-enkephalin may play a role in neural maturation. The aim of the present study was to describe the spatiotemporal pattern of somatostatin and leu-enkephalin immunoreactivity in the auditory brainstem nuclei of the developing rat and to correlate it with other developmental events. In order to achieve this goal, we applied peroxidase-antiperoxidase immunocytochemistry to rat brains between embryonic day (E) 17 and adulthood. Somatostatin immunoreactivity (SIR) was found in all nuclei of the auditory brainstem, yet it was temporally restricted in most nuclei. SIR appeared prenatally and reached maximum levels around postnatal day (P) 7, when great numbers of immunoreactive neurons were present in the ventral cochlear nucleus (VCN) and in the lateral lemniscus. At that time relatively low numbers of cells were labeled in the dorsal cochlear nucleus, the lateral superior olive (LSO), and the inferior colliculus (IC). During the same period, when somata in the VCN were somatostatin-immunoreactive (SIR), a dense network of labeled fibers was also present in the LSO, the medial superior olive (MSO), and the medial nucleus of the trapezoid body (MNTB). As these nuclei receive direct input from VCN neurons, and as the distribution and morphology of the somatostatinergic fibers in the superior olivary complex (SOC) was like that of axons from VCN neurons, these findings suggest a transient somatostatinergic connection within the auditory system. Aside from the LSO, MSO, and MNTB, labeled fibers were found to a smaller extent in all other auditory brainstem nuclei. After P7, the SIR decreased and only a few immunoreactive elements were found in the adult auditory brainstem nuclei, indicating

  16. Effect of behavior training on learning, memory and the expression of NR2B, GluR1 in hippocampus of rats offspring with fetal growth restriction

    Institute of Scientific and Technical Information of China (English)

    Chunfang Li; Wenli Gou; Yunping Sun; Huang Pu

    2008-01-01

    Objective: To study effects of behavior training on learning, memory and the expression of NR2B, GIuR1 in hippocampus of rat's offspring with fetal growth restricfion(FGR). Methods: The rat model of FGR was established by passive smoking method. The rats offspring were divided into the FGR group and the control group, then randomly divided into the trained and untrained group, respectively. Morris water maze test was procezded on postnatal month(PM2/4) as a behavior training method, then the learning-memory of rats was detected through dark-avoidance and step-down tests. The expressions of NR2B and GluR1 suhunits in hippocampal CA1 and CA3 areas were detected by immunohistochemical method. Results: In the dark-avoidance and step-down tests, the performance record of rats with FGR was worse than that of control rats, and the behavior-trained rats was better than the untrained rats, when the FGR model and training factors were analyzed singly. The model factor and training factor had significant interacfion(P < 0.05). The expressions of NR2B and GIuR1 subunits in hippocampal CA1 and CA3 areas of rats with FGR reduced. In contrast, the expressions of GIuR1 and NR2B subunits in CA1 area of behavior-trained rats increased, when the FGR model and training factors were analyzed singly. Conclusion: These findings suggested that the effect of behavior training on the expressions of NR2B and GiuR1 subunits in CA1 area should be the mechanistic basis for the training-induced improvement in learning-memory abilities.

  17. Iodothyronine deiodinase activities in fetal rat tissues at several levels of iodine deficiency: a role for the skin in 3,5,3'-triiodothyronine economy?

    Science.gov (United States)

    Schröder-van der Elst, J P; van der Heide, D; Morreale de Escobar, G; Obregón, M J

    1998-05-01

    Iodothyronine deiodinases, types I, II, and III (D1, D2, and D3) activities were measured in tissues of fetal rats, at 18 and 21 days of gestation, at several levels of iodine deficiency (ID): mild ID diet (MID) and moderately severe ID, MID + 0.005% perchlorate (MID+P). D2 was present in fetal skin, increased between days 18 and 21, and also in MID and MID+P. In skin, D3 increased during ID at day 18, whereas there was a decrease at day 21. Skin T4 decreased in MID and MID+P, showing an inverse relationship with D2. Skin T3 decreased at day 18 in MID and MID+P but increased at day 21, probably because of the increased D2 and decreased D3, maintaining T3 concentrations. No effect of ID was observed on hepatic D1. D2 increased in brain and brown adipose tissue at day 21 in MID+P. No changes were found in maternal placental D2 and D3, but D2 and D3 increased in the fetal placenta at day 18 in MID+P. A higher level of D2 is present in fetal skin than in the brain. As the activity is increased, in even mild ID (and already at 18 days) it can be concluded that skin D2 is likely to be of considerable physiological importance, at least for fetal thyroid hormone economy, by contributing to the intracellular T3 content of the skin and, possibly, to the plasma T3.

  18. Xenon and sevoflurane provide analgesia during labor and fetal brain protection in a perinatal rat model of hypoxia-ischemia.

    Directory of Open Access Journals (Sweden)

    Ting Yang

    Full Text Available It is not possible to identify all pregnancies at risk of neonatal hypoxic-ischemic encephalopathy (HIE. Many women use some form of analgesia during childbirth and some anesthetic agents have been shown to be neuroprotective when used as analgesics at subanesthetic concentrations. In this study we sought to understand the effects of two anesthetic agents with presumptive analgesic activity and known preconditioning-neuroprotective properties (sevoflurane or xenon, in reducing hypoxia-induced brain damage in a model of intrauterine perinatal asphyxia. The analgesic and neuroprotective effects at subanesthetic levels of sevoflurane (0.35% or xenon (35% were tested in a rat model of intrauterine perinatal asphyxia. Analgesic effects were measured by assessing maternal behavior and spinal cord dorsal horn neuronal activation using c-Fos. In separate experiments, intrauterine fetal asphyxia was induced four hours after gas exposure; on post-insult day 3 apoptotic cell death was measured by caspase-3 immunostaining in hippocampal neurons and correlated with the number of viable neurons on postnatal day (PND 7. A separate cohort of pups was nurtured by a surrogate mother for 50 days when cognitive testing with Morris water maze was performed. Both anesthetic agents provided analgesia as reflected by a reduction in the number of stretching movements and decreased c-Fos expression in the dorsal horn of the spinal cord. Both agents also reduced the number of caspase-3 positive (apoptotic neurons and increased cell viability in the hippocampus at PND7. These acute histological changes were mirrored by improved cognitive function measured remotely after birth on PND 50 compared to control group. Subanesthetic doses of sevoflurane or xenon provided both analgesia and neuroprotection in this model of intrauterine perinatal asphyxia. These data suggest that anesthetic agents with neuroprotective properties may be effective in preventing HIE and should be

  19. Transcriptional and Posttranscriptional Inhibition of Lysyl Oxidase Expression by Cigarette Smoke Condensate in Cultured Rat Fetal Lung Fibroblasts

    Science.gov (United States)

    Gao, Song; Chen, Keyang; Zhao, Yinzhi; Rich, Celeste B.; Chen, Lijun; Li, Sandy J.; Toselli, Paul; Stone, Phillip; Li, Wande

    2005-01-01

    Lysyl oxidase (LO) catalyzes crosslinking of collagen and elastin essential for maintaining the structural integrity of the lung extracellular matrix (ECM). To understand mechanisms of cigarette smoke (CS)-induced emphysema, we investigated effects of cigarette smoke condensate (CSC), the particulate matter of CS, on LO mRNA expression in cultured rat fetal lung fibroblasts (RFL6). Exposure of RFL6 cells to 0–120 μg CSC/ml for 24 h induced a dose-dependent inhibition of LO steady-state mRNAs, for example, reducing transcript levels to below 10% of the control in cells incubated with 80–120 μg CSC/ml. Nuclear run-on assays indicated a marked reduction in LO relative transcriptional rates amounting to 27.7% of the control in cells treated with 120 μg CSC/ml. The actinomycin D-chase assay showed that CSC enhanced the instability of LO transcripts. The t1/2 for LO mRNA decay was decreased from 24 h in the control to 4.5 h in cells treated with 120 μg CSC/ml. Moreover, 80–120 μg CSC/ml also inhibited LO promoter activity as revealed by suppression of reporter gene expression in cells transfected with LO promoter-luciferase vectors. Thus, inhibition of LO transcription initiation and enhancement of LO mRNA instability both contributed to downregulation of LO steady-state mRNA in CSC-treated cells. Note that inhibition of LO mRNA expression by CSC was closely accompanied by markedly decreased levels of transcripts of collagen type I and tropoelastin, two substrates of LO. Thus, transcriptional perturbation of LO and its substrates may be a critical mechanism for ECM damage in CS-induced emphysema. PMID:15933228

  20. Development of adrenal zonation in fetal rats defined by expression of aldosterone synthase and 11beta-hydroxylase.

    Science.gov (United States)

    Wotus, C; Levay-Young, B K; Rogers, L M; Gomez-Sanchez, C E; Engeland, W C

    1998-10-01

    The adult rat adrenal cortex is comprised of three concentric steroidogenic zones that are morphologically and functionally distinguishable: the zona glomerulosa, zona intermedia, and the zona fasciculata/reticularis. Expression of the zone-specific steroidogenic enzymes, cytochrome P450 aldosterone synthase (P450aldo), and P450 11beta hydroxylase (P45011beta), produced by the zona glomerulosa and zona fasciculata/reticularis, respectively, can be used to define the adrenal cortical cell phenotype of these two zones. In this study, immunohistochemistry and in situ hybridization were used to determine the ontogeny of expression of P450aldo and P45011beta to monitor the pattern of development of the rat adrenal cortex. RIA was used to measure adrenal content of aldosterone and corticosterone, the resulting products of the two enzymatic pathways. Double immunofluorescent staining for both enzymes at gestational day 16 (E16) showed P45011beta protein expressed in cells distributed throughout most of the adrenal intermixed with a separate, but smaller, population of cells expressing P450aldo protein. Whereas expression of P45011beta protein retained a similar pattern of distribution from E16 to adulthood (ignoring distribution of SA-1 positive, presumptive medullary cells), P450aldo protein changed its pattern of distribution by E19, becoming localized in a discontinuous ring of cells adjacent to the capsule. By postnatal day 1, P450aldo protein distribution was similar to that observed in adult glands; P450aldo-positive cells formed a continuous zone underlying the capsule. In situ hybridization showed that the pattern of P45011beta messenger RNA expression paralleled protein expression at all times, whereas P450aldo messenger RNA paralleled protein at E19 and after, but was undetectable before E19. However, adrenal aldosterone and corticosterone, as measured by RIA, were detected by E16, supporting the functional capacity of both phenotypes for all ages studied. These

  1. Ability of tetraploid rat blastocysts to support fetal development after complementation with embryonic stem cells.

    Science.gov (United States)

    Hirabayashi, Masumi; Tamura, Chihiro; Sanbo, Makoto; Goto, Teppei; Kato-Itoh, Megumi; Kobayashi, Toshihiro; Nakauchi, Hiromitsu; Hochi, Shinichi

    2012-06-01

    This study was undertaken to generate rat offspring via tetraploid blastocyst complementation with embryonic stem (ES) cells. Tetraploid blastocysts were prepared by electrofusion of blastomeres from two-cell stage embryos, and subsequent in vivo culture for 4 days. Microinjection into the tetraploid blastocoel of an inner cell mass isolated by immunosurgery resulted in the generation of rat offspring, suggesting the successful contribution of tetraploid blastocysts to their placenta. Tetraploid blastocyst complementation was attempted with a total of 4 ES cell lines (2 lines of female karyotype and 2 lines of male karyotype). In the rESWIv-3i-5 (XX) cell line, normal-sized fetuses with heartbeats were harvested on E11.5 (12.1%), E12.5 (9.5%), and E13.5 (9.1%), but no viable fetuses were detected on E14.5. Similarly, use of the rESWIv-3i-1 (XX) cell line resulted in no viable fetus production on E14.5. Using the rESBLK2i-1 (XY) cell line, viable fetuses were harvested not only on E11.5-E13.5 (2.6-5.5%), but also on E14.5 (3.0%). The transfer of a total of 487 tetraploid blastocysts complemented with rESBLK2i-1 cells resulted in 256 implantation sites (52.6%) on E21.5, but no viable offspring was detected. Use of the rESBLK2i-1/huKO (XY) cell line also resulted in no viable offspring production on E21.5. Analyses of the methylation pattern in differentially methylated regions and transcript level of genes that are imprinted in mice (H19, Meg3, Igf2r, Peg5, and Peg10) in the E14.5 conceptuses indicated a marked difference between the ES cell-derived and control normal fetuses, but not between the tetraploid and control diploid placenta.

  2. Inhibition and recovery of maternal and fetal cholinesterase enzyme activity following a single cutaneous dose of methyl parathion and diazinon, alone and in combination, in pregnant rats.

    Science.gov (United States)

    Abu-Qare, A W; Abou-Donia, M B

    2001-01-01

    Pregnant Sprague-Dawley rats (14-18 days of gestation) were treated with a single cutaneous subclinical dose(s) of 10 mg kg(-1) (15% of LD(50)) of methyl parathion (O,O-dimethyl O-4-nitrophenyl phosphorothioate) and 65 mg kg(-1) (15% of LD(50)) of diazinon (O,O)-diethyl O-2-isopropyl-6-methylpyrimidinyl phosphorothioate, and their combination. Animals were sacrificed at 1, 2, 4, 12, 24, 48, 72, and 96 h after dosing. Inhibition of maternal and fetal cholinesterase enzyme activity has been determined. Methyl parathion significantly inhibited maternal and fetal brain acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BuChE) activity within 24 h after dosing. Diazinon and a mixture of methyl parathion and diazinon caused lesser inhibition compared with methyl parathion alone. Recovery of maternal and fetal brain AChE activity was in the order of diazinon > combination of diazinon and methyl parathion > methyl parathion 96 h after dosing. Although fetal plasma BuChE activity recovered to 100% of control within 96 h of application, maternal BuChE activity remained inhibited to 55% and 32% of control 96 h after application of methyl parathion and a mixture of methyl parathion and diazinon, respectively. Following a single dermal dose of methyl parathion, the activity of maternal liver BuChE was 63% of control 2 h after dosing, whereas inhibition of placental AChE or BuChE activity occurred 12 and 1 h following a single dose of methyl parathion, corresponding to activities of 63% and 54% of control, respectively. Diazinon, alone or in combination with methyl parathion, did not inhibit significantly the maternal liver BuChE or placental AChE and BuChE activity. The results suggest that dermal application of a single dose of methyl parathion and diazinon, alone or in combination, has an easy access into maternal and fetal tissues, resulting in inhibition of cholinesterase enzymes. The lower inhibitory effect of the combination of methyl parathion and diazinon

  3. Abnormal innervation patterns in the anorectum of ETU-induced fetal rats with anorectal malformations.

    Science.gov (United States)

    Wang, Weilin; Jia, Huimin; Zhang, Hailan; Chen, Qingjiang; Zhang, Tao; Bai, Yuzuo; Yuan, Zhengwei

    2011-05-16

    To investigate whether anorectal malformations (ARMs) were associated with a global neuromuscular maldevelopment of the lower gastrointestinal (GI) tract and anorectum, the distribution of neuronal markers protein gene product (PGP9.5), nitric oxide synthases (NOs), neuromuscular junction markers (synaptophysin, SYP), interstitial cells of Cajal (ICC) marker (c-kit) within the terminal rectum were analyzed by immunohistochemistry and Western blot in rat embryos with ethylenethiourea (ETU) induced ARMs. From Gestational day16 (Gd16) to Gd21, neural crest-derived cells (NCC) migrated from the proximal gut into the terminal colon, colonising it along its entire length, gradually proliferated and differentiated to innervate the distal gut. From Gd19 to Gd21, significant gross-morphological differences of the anorectum of normal (n=90) and ARMs (n=90) embryos were found. Different myenteric plexus (MPs) development of the anorectum suggested that ARMs were associated with a global abnormal innervation patterns in the anorectum in gestational course and might have some postoperative effect.

  4. Early effects of low doses of ionizing radiation on the fetal cerebral cortex in rats

    Energy Technology Data Exchange (ETDEWEB)

    Norton, S.; Kimler, B.F. (Univ. of Kansas Medical Center, Kansas City (USA))

    1990-11-01

    Pregnant rats were exposed to gamma radiation from a 137Cs irradiator on gestational Day 15. Fetuses that received 0.25, 0.5, 0.75, or 1.0 Gy were examined 24 h after irradiation for changes in the cells of the cerebral mantle of the developing brain. The extent of changes following 0.5 Gy was studied at 3, 6, 12, or 24 h after exposure. Cortical thickness of the cerebral mantle was not significantly altered. The number of pyknotic cells, number of macrophages, nuclear area, and number of mitotic cells were altered in a dose-related way. The number of pyknotic cells was significantly increased at all doses. A positive correlation between the number of pyknotic cells and the number of macrophages developed with time. At 3 h after irradiation about 60% of pyknotic cells were found in the subventricular zone and about 25% in the intermediate zone and cortical plate. The number of such cells in the upper layers of the cortex steadily increased up to 24 h, at which time about 70% of pyknotic cells were in these two layers. The relationship of the movement of pyknotic cells to migration of postmitotic neuroblasts is discussed.

  5. Purification and Identification of Microglia in Fetal Rat Brain%胎大鼠脑内小胶质细胞的分离纯化和鉴定

    Institute of Scientific and Technical Information of China (English)

    马怡然; 马英桓; 颜永红

    2011-01-01

    目的 分离纯化和鉴定胎大鼠脑内小胶质细胞,为小胶质细胞的研究奠定基础.方法 盐酸利多卡因注射液联合机械振摇纯化分离胎大鼠脑内小胶质细胞.免疫荧光技术和流式细胞技术鉴定小胶质细胞的纯度.结果 通过盐酸利多卡因注射液联合机械振摇纯化分离法,得到纯度>98%的小胶质细胞.结论 盐酸利多卡因注射液联合机械振摇纯化分离法是一种能获得较高纯度胎大鼠脑内小胶质细胞的方法.%Objective To explore a method to isolate, purify and identify the microglia in fetal rat brain. Methods Fetal rat microglia cells in brain were isolated and purified by adding lidocaine hydrochloride with shock culturing,and the identification of microglia was completed by immunofluorescence and flow cytometry. Results 98% of microglia cells were successfully collected by the method of adding lidocaine hydrochloride with shock culturing. Conclusion The method of lidocaine hydrochloride with shock culturing can collect microglia with high purity in fetal rat brain.

  6. Effects of caffeine and its reactive metabolites theophylline and theobromine on the differentiating testis.

    Science.gov (United States)

    Pollard, I; Locquet, O; Solvar, A; Magre, S

    2001-01-01

    A previous study in the rat (Pollard et al. 1990) established that caffeine, when administered during pregnancy, significantly inhibited the differentiation of the seminiferous cords and subsequent Leydig cell development in the interstitium. However, that study could not distinguish between the direct effects of caffeine and/or the intermediary secondary toxic effects of metabolites such as theophylline and theobromine. Because the fetus lacks the appropriate enzyme systems, clearance of toxic substances takes place via the placenta and maternal liver. Thus, a suitable in vitro system can effectively differentiate between primary and secondary drug effects. In the present study, 13-day-old fetal testis, at the stage of incipient differentiation, were cultured for 4 days in vitro in the presence of graded doses of caffeine, theophylline or theobromine. It was found that explants exposed to caffeine or theobromine differentiated normally, developing seminiferous cords made up of Sertoli and germ cells, soon followed by the differentiation of functionally active Leydig cells appearing in the newly formed interstitium. However, explants exposed to theophylline failed to develop seminiferous cords and, as a consequence, Leydig cells. In conclusion, insights obtained from different experimental methods, such as organ culture or whole organism studies, are not always identical. It may be prudent, therefore, to take into account that certain experimental techniques, despite providing valuable information, may require confirmation by other test methods in order to obtain an in-depth understanding of mechanisms of action involved.

  7. Safety evaluation of a vaccine: Effect in maternal reproductive outcome and fetal anomaly frequency in rats using a leishmanial vaccine as a model

    Science.gov (United States)

    Soares, Thaigra S.; Silva, Ana Luiza T.; Giunchetti, Rodolfo C.; Takano, Maria A. S.; Akamatsu, Milena A.; Kubrusly, Flávia S.; Lúcio-Macarini, Fernanda; Raw, Isaias; Iourtov, Dmitri; Ho, Paulo Lee; Bueno, Lilian L.; Fujiwara, Ricardo T.; Volpato, Gustavo T.

    2017-01-01

    While the immunogenic potential of the vaccination against infectious diseases was extensively shown, data on the safety assessment of recombinant proteins in vaccine formulations administered during pregnancy are still scarce. In the current study, the antigenicity of a vaccine against leishmaniasis (based on Leishmania braziliensis recombinant protein peroxidoxin) during pregnancy and possible maternal reproductive outcomes and fetal anomalies after immunization with a leishmanial vaccine or adjuvant alone (Bordetella pertussis derived MPLA adjuvant) were assessed. Rats were mated and allocated in three groups: Control—rats received saline; Adjuvant—rats received the adjuvant MPLA, and Vaccine—rats received the combination of MPLA and peroxidoxin. The administration was subcutaneously at the dorsal region, three times (days 0, 7, 14 of pregnancy). On day 21 of pregnancy, all rats were bled for biochemical and immunological measurements. The gravid uterus was weighed with its contents, and the fetuses were analyzed. The immunization with peroxidoxin induced a significant production of circulating IgG levels compared to other groups but caused a significant in post-implantation loss (14.7%) when compared to Control (5.0%) and Adjuvant (4.4%) groups. Furthermore, a significantly high rate of fetal visceral anomalies, such as hydronephrosis and convoluted ureter, was also observed in animals that received vaccine when compared to Control or Adjuvant groups. These data indicate the importance of safety evaluation of vaccines during pregnancy and the limited use of peroxidoxin administration during pregnancy. More importantly, the safety monitoring of immunization with MPLA derived from Bordetella pertussis demonstrated no reproductive outcomes associated with adjuvant administration, suggesting its safe use during pregnancy. PMID:28249007

  8. Gene expression during development of fetal and adult Leydig cells.

    Science.gov (United States)

    Dong, Lei; Jelinsky, Scott A; Finger, Joshua N; Johnston, Daniel S; Kopf, Gregory S; Sottas, Chantal M; Hardy, Matthew P; Ge, Ren-Shan

    2007-12-01

    In rats and mice, Leydig cells are formed as two morphologically and functionally different generations. The first generation develops in utero, from undifferentiated stem Leydig cells (SLCs) that differentiate into fetal Leydig cells (FLCs). After birth, SLCs that may differ from the fetal SLCs undergo lineage-specific commitment and give rise to adult Leydig cells (ALCs). The intermediates of ALCs first become apparent by day 11 postpartum. These first-appearing intermediates, progenitor Leydig cells (PLCs), are spindle shaped and identifiable as steroidogenic because they express luteinizing hormone receptor (LHR) and 3beta-hydroxysteroid dehydrogenase (3betaHSD). The next step in the transition of PLCs to ALCs is the appearance of the immature Leydig cells (ILCs), most commonly seen in the testis during days 28 to 56 postpartum. ILCs have a more abundant smooth endoplasm reticulum (SER), the network of membranes providing a scaffold for steroidogenic enzyme localization, compared to PLCs, but are considered immature because they secrete higher levels of 5alpha-reduced androgen than testosterone. ILCs undergo a final division before ALC steroidogenic function matures by postnatal day 56. ALCs mark the point of maximum differentiation, and at this stage, the Leydig cell secretes testosterone at the highest rate. In this review, trends of gene expression during development of the two Leydig-cell generations, and recent information from gene profiling by microarray, are evaluated. The expression profiles are distinct, indicating that FLCs and ALCs may originate from separate pools of stem cells.

  9. Effects of cytotoxic deletions of somatic sensory cortex in fetal rats.

    Science.gov (United States)

    Yurkewicz, L; Valentino, K L; Floeter, M K; Fleshman, J W; Jones, E G

    1984-01-01

    Pregnant rats were injected on the 14th day of gestation with the cytotoxic drug methylazoxymethanol acetate. This compound causes the death of neural precursor cells that were synthesizing DNA at the time of injection. After birth, the progeny of treated mothers grew to maturity with a neocortex that was greatly reduced in area by the death of all cells, particularly at the frontal and occipital poles but at medial and lateral margins of neocortex as well. In the remaining cortex layers II through IV failed to develop. The experiment deprived growing thalamocortical axons, which innervate the somatic sensory cortex late in development, of part of their normal target area and of a substantial number of their definitive target cells. It also deprived them of any cues they might have received from these target cells migrating through them as the axons accumulate beneath the cortical plate. Anatomical experiments indicated that, despite these defects, thalamocortical axons could still colonize the sensorimotor areas and form synapses in their typically bilaminar pattern, though the outer, denser lamina of terminations occurred abnormally at the level of the apices of layer V pyramidal cell bodies. Receptive field mapping of single and multiunit responses in the somatic sensory region showed brisk responses and receptive fields of normal size. It also indicated the formation of a body map that was topographically intact except for deletions at its periphery; that is, a total map was not compressed into a smaller area. This suggests that somatic sensory thalamocortical fibers recognize only remaining cortical target cells in appropriate fields. Moreover, successful ones among them seem to recognize neighborhood relations and conserve synaptic space at the expense of those that would have innervated the deleted peripheral parts of the area. Pyramidal neurons in the remaining cortical layers and in ectopic islands of cells that had incompletely migrated from the

  10. Effect of Hydro Alcoholic Ginger Extracts on the Body Weight, Testis Weight and Spermatogenesis in Male Rats Undergoing Chemotherapy with Cyclophosphamide

    Directory of Open Access Journals (Sweden)

    E Sharifi

    2010-03-01

    Full Text Available Introduction: Cyclophosphamide is used as an anti cancer medicine in chemotherapy. This is an alkalizing medicine and causes the binding of DNA strands, breaking of DNA and control of protein synthesis and RNA. The side effects of this medicine include lack of appetite, nausea, reduction in activity of sexual lymph nodes, causing amenorrhea, azoospermia and oligospermia. Ginger includes many compounds, some of which are shogaols, gingerols, pyrogallols and sesquiterpenes. Ginger has anti nauseating, anti cancer, anti oxidant effects and eliminates free radicals. This medicine is used along with cyclophosphamide to reduce its destructive side effects in the body. Methods: For 21 days, the rats were fed with ginger and cyclophosphamide. After 21 days, the animals were weighed and rendered unconscious. Their testes were removed and tissue samples were provided from their testes. Results: The results showed that cyclophosphamide alone reduces body weight, testes weight and spermatogenesis as compared to the control group. In other experimental groups that were fed with ginger and cyclophosphamide, increased dosage of ginger increased the body weight, the testes weight and spermatogenesis in comparison to the other experimental groups. Conclusion: It seems that compounds present in ginger are anti tumoral and control the production of active metabolites. Therefore, if administered together with Cyclophosphamide, it can be useful and effective in patients undergoing chemotherapy.

  11. Analysis by immunocytochemistry and in situ hybridization of renin and its mRNA in kidney, testis, adrenal, and pituitary of the rat.

    Science.gov (United States)

    Deschepper, C F; Mellon, S H; Cumin, F; Baxter, J D; Ganong, W F

    1986-01-01

    Renin gene expression in cells and tissues of the rat was examined by in situ hybridization histochemistry and immunocytochemistry. By using a mouse cDNA probe, hybridization histochemistry revealed renin mRNA in the renal juxtaglomerular cells, testicular Leydig cells, adrenal zona glomerulosa cells, the intermediate lobe of the pituitary, and scattered cells of the anterior lobe of the pituitary. With four separate antisera to mouse submaxillary renin, there was immunoreactivity in the renal juxtaglomerular cells. However, only one of the antisera stained the Leydig cells, a second stained the adrenal zona glomerulosa, a third stained the intermediate lobe of the pituitary, and a fourth stained scattered cells of the anterior lobe of the pituitary that were identified as gonadotrophs. The variations with the different antisera in detecting extrarenal renin are unexplained but could imply that posttranslational proteolysis or glycosylation of preprorenin varies in different tissues with consequent variations in immunoreactivity. The finding of renin mRNA and renin-like immunoreactivity in these tissues supports the notion that these tissues are sites for production of renin. Images PMID:3532116

  12. 妊娠期糖尿病大鼠胎膜中水通道蛋白8mRNA的表达%The expression of mRNA of aquaporin 8 in fetal membrane of gestationai diabetes mellitus rats

    Institute of Scientific and Technical Information of China (English)

    刘广智; 刘金梅; 王志军; 郭小丽; 姚玉洁

    2012-01-01

    目的 探讨在影响妊娠期糖尿病大鼠胎膜通透性方面的可能机制.方法 选取造模成功的妊娠期糖尿病大鼠(模型组)和正常妊娠大鼠(对照组)各30只,在妊娠19 d时于无菌条件下留取大小1.0 cm×1.0 cm胎膜2块,采用RT-PCR反应检测胎膜中AQP8 mRNA的表达.结果 2组大鼠胎膜上均有AQP8 mRNA的表达,且AQP8 mRNA在模型组大鼠胎膜上的表达明显低于对照组(P<0.05).结论 水通道蛋白8 mRNA在孕足月大鼠胎膜有表达,其在妊娠期糖尿病大鼠胎膜中的表达降低可能参与了羊水量异常的调控.%Objectives To investigate the possible mechanism of permeability changes in fetal membrane of gestational diabetes mellitus ( GDM) rats by detecting the aquaporin 8 ( AQP8 ) gene' s expression in the fetal membrane by using the reverse transcription - polymerase chain reaction ( RT-PCR) technique. Methods The 30 gestational diabetic rats (model group) and 30 normal full-term pregnancy rats (control group) were enrolled in the study. At 19 days after pregnancy, two pieces of fetal membranes with size about 1. 0 cm x 1. 0 cm were taken out under sterile condition, and the expression of AQP8 mRNA in fetal membrane was detected by RT-PCR. Results The both groups showed the expression of AQP8 mRNA in fetal membrane of rats, furthermore, the expression of AQP8 mRNA in fetal membrane of the rats of model group was significantly lower than that of rats in control group ( P < 0. 05 )*. Conclusion The aquaporins 8 mRNA expresses in the fetal membrane of full-term pregnancy rats,and the decrease of expression in the fetal membrane of gestational diabetic mellitus rats may be involved in the regulation of the abnormality of amniotic fluid amount.

  13. Antagonism of glutathione to oxidative injury induced by manganese in rats testis%谷胱甘肽拮抗锰致雄性大鼠生殖损伤的研究

    Institute of Scientific and Technical Information of China (English)

    王乾兴; 金华; 张先平

    2011-01-01

    Objective: To explore the antagonism of glutathione to oxidative injury induced by manganese in rats testis. Methods ; Forty - eight healthy male SD rats were randomly divided into 3 groups. The rats of manganese exposure group were treated with 30mg/kg MnCl2· 4H2O for 1 week or4 weeks, followed by 1mmol/Kg glutathione (CSH ) for 2 weeks. The control group were received normal saline. The spermatogenic cell apoptosis was detected by terminal deoxynucleotidyl transferase -mediated Dutp nick end labeling technique. The malondialdehyde ( MDA) concentration and the glutathione peroxidase (CSH - Px) activity were measured by colorimetric analysis. Results: When the rats were exposured to manganese for 1 week, the apoptotic index ( AI) of spermatogenic cells and testicular MDA content of manganese exposure group were significantly higher than those of CSH antagonistic group and the control group ( P <0.01). CSH - Px activity showed no significant difference among the three groups. When manganese exposure for 4 weeks, AI of spermatogenic cells and testicular MDA content in manganese exposure group were significantly higher than those in CSH antagonist group and the control group ( P < 0.01) , meanwhile that in CSH antagonist group were also higher when compared with the control group (P <0.01). The activity of CSH - Px in manganese exposure group was significantly lower than those of CSH antagonistic group and the control group (P<0.01). Conclusion; Timely supplement of glutathione could decrease spermatogenic cell apoptosis through inhibiting lipid peroxidation induced by manganese.%目的:研究谷胱甘肽(GSH)对锰致雄性大鼠睾丸氧化损伤的拮抗作用.方法:将48只健康雄性SD大鼠随机分为3组进行急性和亚急性染毒.染锰组腹腔注射30mg/kg MnCl2·4H2O染毒1周(急性染毒)和4周(亚急性染毒),GSH拮抗组染毒后再给予2周1mmol/kg GSH,对照组染毒后给予生理盐水.TUNEL法检测生精细胞凋亡;化学比色法检

  14. Maternal obesity induced by a 'cafeteria' diet in the rat does not increase inflammation in maternal, placental or fetal tissues in late gestation.

    Science.gov (United States)

    Crew, Rachael C; Waddell, Brendan J; Mark, Peter J

    2016-03-01

    Obesity during pregnancy can cause serious complications for maternal and infant health. While this has often been attributed to increased inflammation during obese pregnancy, human and animal studies exhibit variable results with respect to the inflammatory status of the mother, placenta and fetus. Cafeteria (CAF) feeding induces more inflammation than standard high-fat feeding in non-pregnant animal models. This study investigated whether maternal obesity induced by a CAF diet increases maternal, fetal or placental inflammation. Maternal obesity was established in rats by 8 weeks of pre-pregnancy CAF feeding. Maternal plasma inflammatory markers (IL-1β, IL-6, IL-10, IL-12p40, MCP1, GRO/KC, MIP-2 and TNFα) and expression of inflammatory genes (Tnfα, Il-6, Il-1β, Tlr2, Tlr4, Cox2 and Emr1) in maternal, placental and fetal tissues were measured at day 21 of gestation. Despite CAF animals having 63% more central body fat than controls at day 21 of gestation, plasma inflammatory markers were not increased; indeed, levels of IL-6, IL-12p40 and MIP2 were reduced slightly. Similarly, inflammatory gene expression remained largely unaffected by CAF feeding, except for slight reductions to Tlr4 and Emr1 expression in CAF maternal adipose tissue, and reduced Tlr4 expression in male labyrinth zone (LZ). The junctional zone (JZ) displayed increased Il-6 expression in CAF animals when fetal sexes were combined, but no inflammatory genes were affected by the CAF diet in fetal liver. Maternal obesity induced by a CAF diet before and during pregnancy does not increase the inflammatory status of the mother, placenta or fetus in late gestation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Morphology of the Testis and Epididymis of Large White Boars

    Directory of Open Access Journals (Sweden)

    Samuel Gbadebo Olukole

    2016-06-01

    Full Text Available The testis and epididymis of twenty five adult Large White boars were used to investigate the biometric and histomorphometric parameters of the testis and epididymis of the boars. The aim of the study was to provide information which could be useful in the comparative regional anatomy of the male reproductive organs of domestic animals and thus an improved assessment of breeding soundness and fertility potential in boars. The average weight of the animals was 71.3 ± 10.7 kg. The average weights of the right and left testes were 170 ± 0.7.60 g and 179±6.48g, respectively with no significant dif¬ference. The average weights of the right and left epididymis were 40.9 ± 6.81 g and 43.7 ± 8.55 g, respectively, with no significant difference. The relative testicular and epididymal weights were 0.49% and 0.12%, respectively. This study shows that the testis is about four times the size of the epididymis. The ductal diameter of the head, body and tail of the epididymis were 418 ± 22.6 µm, 432 ± 20.3 µm and 939 ± 50.6 µm, respectively. The mean relative volume of the germinal epithelium, interstitium and lumen of the seminiferous tubules of the boars rats were 68.4 ± 3.46%, 5.5 ± 0.66% and 78.0 ± 4.81%, respectively. It can be concluded that the morphology of the testis and epididymis of the Large White boar are similar to those of most mammals. This work provides information the testis and epididymis of the Large White boar which could be useful in the comparative regional anatomy of the male reproductive organs of domestic animals and thus an improved assessment of breeding soundness and fertility potential in boars.

  16. Outcomes of Testis Sparing Surgery

    Directory of Open Access Journals (Sweden)

    Muhammet Özcan

    2012-09-01

    Full Text Available Aim: Our aim was to review the indications and results of partial orchidectomy. Material and Method: We retrospectively investigated pathologic and demographic features of patients who underwent partial orchidectomy between February 2005 and December 2011. Results: Partial orchidectomy was performed on 7 patients aged between 2 and 30 years. Partial orchidectomy was performed for testicular tumour/mass on solitary testis, bilateral testicular tumour, trauma on 3,2,1 patients respectively. Pathologic examination of the patient who was undergone partial orchiectomy for testicular trauma revealed a mixed germ cell tumour that was detected incidentally. Discussion: Testis sparing surgery is a treatment option in selected cases with the davantages of fertility preservation and avoiding the need for long-term hormone replacement therapy.

  17. Cancer testis antigen and immunotherapy

    Directory of Open Access Journals (Sweden)

    Krishnadas DK

    2013-04-01

    Full Text Available Deepa Kolaseri Krishnadas, Fanqi Bai, Kenneth G Lucas Department of Pediatrics, Division of Hematology/Oncology, University of Louisville, KY, USA Abstract: The identification of cancer testis (CT antigens has been an important advance in determining potential targets for cancer immunotherapy. Multiple previous studies have shown that CT antigen vaccines, using both peptides and dendritic cell vaccines, can elicit clinical and immunologic responses in several different tumors. This review details the expression of melanoma antigen family A, 1 (MAGE-A1, melanoma antigen family A, 3 (MAGE-A3, and New York esophageal squamous cell carcinoma-1 (NY-ESO-1 in various malignancies, and presents our current understanding of CT antigen based immunotherapy. Keywords: cancer testis antigens, immunotherapy, vaccine

  18. Vigilancia Fetal

    OpenAIRE

    SAONA UGARTE, Pedro

    2013-01-01

    La percepción de la actividad fetal por la madre es la técnica más antigua y menos costosa de controlar el bienestar fetal. Tradicionalmente se ha considerado la disminución o ausencia de movimientos fetales percibidos por la madre, como una señal de alarma, en especial cuando existe insuficiencia útero placentaria. Varios investigadores han descrito el valor del registro diario de movimientos fetales como un método para identificar el feto en peligrote morir. El poder discernir si el feto se...

  19. Lack of action of exogenously administered T3 on the fetal rat brain despite expression of the monocarboxylate transporter 8

    OpenAIRE

    Grijota Martínez, María del Carmen; Díez, Diego; Morreale de Escobar, Gabriella; Bernal, Juan; Morte, Beatriz

    2011-01-01

    Mutations of the monocarboxylate transporter 8 gene (MCT8, SLC16A2) cause the Allan-Herndon-Dudley syndrome, an X-linked syndrome of severe intellectual deficit and neurological impairment. Mct8 transports thyroid hormones (T4 and T3), and the Allan-Herndon-Dudley syndrome is likely caused by lack of T3 transport to neurons during critical periods of fetal brain development. To evaluate the role of Mct8 in thyroid hormone action in the fetal brain we administered T4 or T3 to thyroidectomized ...

  20. Aristaless related homeobox gene, Arx, is implicated in mouse fetal Leydig cell differentiation possibly through expressing in the progenitor cells.

    Directory of Open Access Journals (Sweden)

    Kanako Miyabayashi

    Full Text Available Development of the testis begins with the expression of the SRY gene in pre-Sertoli cells. Soon after, testis cords containing Sertoli and germ cells are formed and fetal Leydig cells subsequently develop in the interstitial space. Studies using knockout mice have indicated that multiple genes encoding growth factors and transcription factors are implicated in fetal Leydig cell differentiation. Previously, we demonstrated that the Arx gene is implicated in this process. However, how ARX regulates Leydig cell differentiation remained unknown. In this study, we examined Arx KO testes and revealed that fetal Leydig cell numbers largely decrease throughout the fetal life. Since our study shows that fetal Leydig cells rarely proliferate, this decrease in the KO testes is thought to be due to defects of fetal Leydig progenitor cells. In sexually indifferent fetal gonads of wild type, ARX was expressed in the coelomic epithelial cells and cells underneath the epithelium as well as cells at the gonad-mesonephros border, both of which have been described to contain progenitors of fetal Leydig cells. After testis differentiation, ARX was expressed in a large population of the interstitial cells but not in fetal Leydig cells, raising the possibility that ARX-positive cells contain fetal Leydig progenitor cells. When examining marker gene expression, we observed cells as if they were differentiating into fetal Leydig cells from the progenitor cells. Based on these results, we propose that ARX acts as a positive factor for differentiation of fetal Leydig cells through functioning at the progenitor stage.

  1. Comments on Li et al. Effects of in Utero Exposure to Dicyclohexyl Phthalate on Rat Fetal Leydig Cells. Int. J. Environ. Res. Public Health 2016, 13, 246

    DEFF Research Database (Denmark)

    Svingen, Terje

    2016-01-01

    Profiling the expression levels of genes or proteins in tissues comprising two or more cell types is commonplace in biological sciences. Such analyses present particular challenges, however, for example a potential shift in cellular composition, or ‘cellularity’, between specimens. That is, does ...... the mammalian testis and a recent study on the effects of phthalate exposure on testis function as an example....

  2. Effects of ultra-wideband electromagnetic irradiation on the ultrastructure of rat pituitary and testis and sex hormones of rat%超宽带电磁辐射对大鼠垂体和睾丸超微结构及性激素水平的影响

    Institute of Scientific and Technical Information of China (English)

    杨明娟; 苗霞; 刘海强; 侯知佑; 曾丽华; 郭国祯

    2011-01-01

    目的 观察超宽带(ultra-wideband,UWB)电磁辐射对大鼠垂体和睾丸超微结构以及血清中性激素水平的影响。方法 将SD雄性大鼠随机分为辐照组和对照组。辐照组大鼠接受脉冲数为30万次的UWB辐照,并于辐照后6、12、24、48 h,应用透射电子显微镜观察垂体及睾丸超微结构的改变,放射免疫法检测大鼠血清中睾酮(T)、黄体生成素(LH)及促卵泡激素(FSH)水平。结果 在辐照后各时间点,大鼠垂体和睾丸均出现不同程度的损伤。在辐照后24h,垂体和睾丸损伤程度最重。垂体嗜碱细胞内质网扩张,胞浆中有空泡,出现脂滴,淋巴细胞渗出,染色质边集;睾丸组织中,精原细胞、支持细胞和间质细胞均出现染色质边集、内质网扩张,毛细血管内皮细胞线粒体肿胀、空泡化,淋巴细胞渗出。辐照组血清中T水平在辐照后24、48 h分别为(1209.7±115.7)、(1340.5±331.1)μg/L,明显低于相应对照组f分别为(2721.8±178.9)、(2820.9±321.4) μg/L],差异均有统计学意义(P<0.05),而LH和FSH均未发生明显改变。结论 UWB电磁辐射可导致大鼠垂体和睾丸超微结构发生变化,对大鼠血清中T含量有一定程度的影响,可能是UWB辐照引起大鼠生殖系统发生改变的原因之一。%Objective To observe the effects of ultra-wideband (UWB) electromagnetic irradiation on the ultrastructure of pituitary or testis and the serum sex hormones level of in rats. Methods SD male rats were divided randomly into control group and irradiation groups exposed to 3×105 pulses UWB irradiation for 6,12, 24, 48 h. After exposure, the ultrastructure changes of pituitary and testis were observed by electron microscope. Serum testosterone (T) , luteinizing hormone (LH) and follicle stimulating hormone (FSH) were measured by radioimmunoassay. Results The rat pituitary and testis were injured at the different time after exposure to UWB

  3. The intrauterine metabolic environment modulates the gene expression pattern in fetal rat islets: prevention by maternal taurine supplementation

    DEFF Research Database (Denmark)

    Reusens, B; Sparre, T; Kalbe, L;

    2008-01-01

    is decreased at birth and metabolic perturbation lasts through adulthood even though a normal diet is given after birth or after weaning. Maternal and fetal plasma taurine levels are suboptimal. Maternal taurine supplementation prevents these induced abnormalities. In this study, we aimed to reveal changes...

  4. Characterisation of the maternal response to chronic phase shifts during gestation in the rat: implications for fetal metabolic programming.

    Directory of Open Access Journals (Sweden)

    Tamara J Varcoe

    Full Text Available Disrupting maternal circadian rhythms through exposure to chronic phase shifts of the photoperiod has lifelong consequences for the metabolic homeostasis of the fetus, such that offspring develop increased adiposity, hyperinsulinaemia and poor glucose and insulin tolerance. In an attempt to determine the mechanisms by which these poor metabolic outcomes arise, we investigated the impact of chronic phase shifts (CPS on maternal and fetal hormonal, metabolic and circadian rhythms. We assessed weight gain and food consumption of dams exposed to either CPS or control lighting conditions throughout gestation. At day 20, dams were assessed for plasma hormone and metabolite concentrations and glucose and insulin tolerance. Additionally, the expression of a range of circadian and metabolic genes was assessed in maternal, placental and fetal tissue. Control and CPS dams consumed the same amount of food, yet CPS dams gained 70% less weight during the first week of gestation. At day 20, CPS dams had reduced retroperitoneal fat pad weight (-15%, and time-of-day dependent decreases in liver weight, whereas fetal and placental weight was not affected. Melatonin secretion was not altered, yet the timing of corticosterone, leptin, glucose, insulin, free fatty acids, triglycerides and cholesterol concentrations were profoundly disrupted. The expression of gluconeogenic and circadian clock genes in maternal and fetal liver became either arrhythmic or were in antiphase to the controls. These results demonstrate that disruptions of the photoperiod can severely disrupt normal circadian profiles of plasma hormones and metabolites, as well as gene expression in maternal and fetal tissues. Disruptions in the timing of food consumption and the downstream metabolic processes required to utilise that food, may lead to reduced efficiency of growth such that maternal weight gain is reduced during early embryonic development. It is these perturbations that may contribute to

  5. The pathogenicitv of melamine on fetal kidney in SD rats%三聚氰胺对SD胎鼠肾脏致病性研究

    Institute of Scientific and Technical Information of China (English)

    蔡仕彬; 吴玉; 冯洋; 刘智涛; 苏萍; 王继红; 杜永洪

    2011-01-01

    and yellow precipitates were not found in kidneys of 720 mg/( kg· d ) dose group. Tubules dearly expanded. Conclusion: Melamine could penetrate into fetal rats through placental barrier, and accumulate in the kidney, which may result in the injury of the growth and development of fetal rat kidney.

  6. Early Life Exposure to Fructose Alters Maternal, Fetal and Neonatal Hepatic Gene Expression and Leads to Sex-Dependent Changes in Lipid Metabolism in Rat Offspring.

    Science.gov (United States)

    Clayton, Zoe E; Vickers, Mark H; Bernal, Angelica; Yap, Cassandra; Sloboda, Deborah M

    2015-01-01

    Fructose consumption is associated with altered hepatic function and metabolic compromise and not surprisingly has become a focus for perinatal studies. We have previously shown that maternal fructose intake results in sex specific changes in fetal, placental and neonatal outcomes. In this follow-up study we investigated effects on maternal, fetal and neonatal hepatic fatty acid metabolism and immune modulation. Pregnant rats were randomised to either control (CON) or high-fructose (FR) diets. Fructose was given in solution and comprised 20% of total caloric intake. Blood and liver samples were collected at embryonic day 21 (E21) and postnatal day (P)10. Maternal liver samples were also collected at E21 and P10. Liver triglyceride and glycogen content was measured with standard assays. Hepatic gene expression was measured with qPCR. Maternal fructose intake during pregnancy resulted in maternal hepatic ER stress, hepatocellular injury and increased levels of genes that favour lipogenesis. These changes were associated with a reduction in the NLRP3 inflammasome. Fetuses of mothers fed a high fructose diet displayed increased hepatic fructose transporter and reduced fructokinase mRNA levels and by 10 days of postnatal age, also have hepatic ER stress, and elevated IL1β mRNA levels. At P10, FR neonates demonstrated increased hepatic triglyceride content and particularly in males, associated changes in the expression of genes regulating beta oxidation and the NLRP3 inflammasome. Further, prenatal fructose results in sex-dependant changes in levels of key clock genes. Maternal fructose intake results in age and sex-specific alterations in maternal fetal and neonatal free fatty acid metabolism, which may be associated in disruptions in core clock gene machinery. How these changes are associated with hepatic inflammatory processes is still unclear, although suppression of the hepatic inflammasome, as least in mothers and male neonates may point to impaired immune sensing.

  7. 牙周炎与胎鼠生长受限相关性的实验研究%The experiment study between periodontitis and fetal growth restriction in rats

    Institute of Scientific and Technical Information of China (English)

    田宗蕊; 林垚; 台保军; 江汉; 杜民权

    2012-01-01

    Objectine: To study the relationship between periodontitis and fetal growth restriction in rats on the basis of the establishment of periodontitis and pregnancy rat model. Method:11 female SD rats were ligated thread in bilateral mandibular first molar. 7 female SD rats belonged to the control group. The female rats mated male rats 2 weeks later and were killed before production. We collected maternal heart blood and rat fetal.measured fetal weight and crown- rump length, tested the concentrations of tumor necrosis factor-α (TTSF-α) in maternal serum by ELISA technology. Result: The incidence of fetal growth restriction in the periodontitis group was 8.3 %> significantly higher than that in the control group. The serum concentrations of TNF-α in pregnant rats which prouducted fetal growth restriction in the periodontitis group was significantly higher than that in the control group. (P < 0.05). Conclusion: Periodontitis is a risk factor for fetal growth restriction, and it may be associated with the changing of cytokine such as TNF-a induced by periodontitis.%目的:在建立大鼠牙周炎及大鼠怀孕模型基础上,研究牙周炎与生长受限胎鼠之间的相关关系.方法:11只雌性SD大鼠双侧下颌第一磨牙丝线结扎制作牙周炎动物模型,7只雌性SD大鼠作对照组,2周后将雌鼠与雄鼠合笼建立大鼠怀孕模型.分娩前处死孕鼠,收集孕鼠心脏血、胎鼠,测量胎鼠体重、顶臀长度,ELISA方法检测孕鼠血清中肿瘤坏死因子-α(TNF-α)的浓度.结果:牙周炎组中胎鼠生长受限的发生率为8.3%,显著高于对照组胎鼠生长受限的发生率.牙周炎组生长受限胎鼠的孕鼠TNF-α血清浓度显著高于对照组孕鼠血清浓度(P<0.05).结论:牙周炎是胎鼠生长受限发生的危险因素,可能与牙周局部感染引起血液中TNF-a等炎性细胞因子的改变有关.

  8. Distinct efficacy of pre-differentiated versus intact fetal mesencephalon-derived human neural progenitor cells in alleviating rat model of Parkinson's disease

    Institute of Scientific and Technical Information of China (English)

    XuanWang; YanyanLu; HuanqingZhang; KunWang; QihuaHe; YueWang; XianyuLiu; LinsongLi; XiaominWang

    2005-01-01

    Neural progenitor cells have shown tile effectiveness in the treatment of Parkinson's disease, but tile therapeutic efficacy remains variable. One of important factors that determine the efficacy is the necessity ofpre-differentiation of progenitor cells into dopaminergic neurons before transplantation. This study therefore investigated the therapeutic efficacy of mesencephalon-derived human neural progenitor cells with or without the pre-differentiation in alleviating a rat model of Parkinson's disease. We found that a combination of 50ng/ml fibroblast growth factor 8, 10ng/ml glial cell line-derived neurotrophic factor and 10μM forskolin facilitated the differentiation of human fetal mesencephalic progenitor cells into dopaminergic neurons in vitro. More importantly, after transplanted into the striatum ofparkinsonian rats, only pre-differentiated grafts resulted in an elevated production ofdopamine in the transplanted site and the amelioration of behavioral impairments of the parkinsonian rats. Unlike pre-differentiated progenitors, grafted intactprogenitors rarely differentiated into dopaminergic neurons in vivo and emigrated actively away from the transplanted site. These data demonstrates the importance ofpre-differentiation of human progenitor cells before transplantation in enhancing therapeutic potency for Parkinson's disease.

  9. Investigation of the protective effect of ellagic acid for preventing kidney injury in rats exposed to nicotine during the fetal period.

    Science.gov (United States)

    Akkoyun, H T; Karadeniz, A

    2016-01-01

    We investigated the possible protective effects of ellagic acid on rat kidneys exposed to nicotine during the fetal period. Twenty pregnant female rats were divided randomly into four groups: control (C), nicotine (N), ellagic acid (EA) and nicotine + ellagic acid (N + EA). Nicotine and ellagic acid treatments were continued throughout the pregnancies and for 15 days after delivery. On day 15, all neonatal pups were sacrificed and their kidneys were removed for biochemical and histopathological examination. The nicotine treatment significantly decreased body weight, total glutathione (GSH), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities, and increased malondialdehyde (MDA) and nitric oxide (NO) levels in the N group compared to controls. EA treatment ameliorated decreased body weight, GSH, GSH-Px and SOD activities, and increased MDA and NO levels in group N + EA compared to group N (p kidney damage as shown by incomplete development of glomeruli and Bowman's capsules. Nicotine also caused greater apoptosis in group N compared to group C. Ellagic acid treatment produced histological kidney structure that was closer to normal and it exerted an anti-apoptotic effect in the N + EA group compared to the N group. EA played a protective role against nicotine-induced nephrotoxicity and oxidative stress in rats owing to its antioxidant, radical scavenging and anti-apoptotic effects.

  10. Convenient and efficient enrichment of the CD133+ liver cells from rat fetal liver cells as a source of liver stem/progenitor cells.

    Science.gov (United States)

    Liu, Wei-hui; Li, Ren; Dou, Ke-feng

    2011-03-01

    Although the stem cells are commonly isolated by FACS or MACS, they are very expensive and these is no specific marker for liver stem/progentior cells (LSPCs). This paper applied a convenient and efficient method to enrich LSPCs. The fetal liver cells (FLCs) were firstly enriched by Percoll discontinuous gradient centrifugation (PDGC) from the rat fetal liver. Then the FLCs in culture were purified to be homogeneous in size by differential trypsinization and differential adherence (DTDA). Flow cytometric analysis revealed more than half of the purified FLCs expressed alternative markers of LSPCs (CD117, c-Met, Sca-1, CD90, CD49f and CD133). In other words, the purified FLCs were heterogeneous. Therefore, they were sequentially layered into six fractions by Percoll continuous gradient centrifugation (PCGC). Both CD133 and CD49f expressed decreasingly from fraction 1 to 6. In fraction 1 and 2, about 85% FLCs expressed CD133, which were revealed to be LSPCs by high expressions of AFP and CK-19, low expressions of G-6-P and ALB. To conclude, the purity of CD133(+) LSPCs enriched by combination of PDGC, DTDA and PCGC is close to that obtained by MACS. This study will greatly contribute to two important biological aspects: liver stem cells isolation and liver cell therapy.

  11. Human ESC-derived dopamine neurons show similar preclinical efficacy and potency to fetal neurons when grafted in a rat model of Parkinson's disease.

    Science.gov (United States)

    Grealish, Shane; Diguet, Elsa; Kirkeby, Agnete; Mattsson, Bengt; Heuer, Andreas; Bramoulle, Yann; Van Camp, Nadja; Perrier, Anselme L; Hantraye, Philippe; Björklund, Anders; Parmar, Malin

    2014-11-06

    Considerable progress has been made in generating fully functional and transplantable dopamine neurons from human embryonic stem cells (hESCs). Before these cells can be used for cell replacement therapy in Parkinson's disease (PD), it is important to verify their functional properties and efficacy in animal models. Here we provide a comprehensive preclinical assessment of hESC-derived midbrain dopamine neurons in a rat model of PD. We show long-term survival and functionality using clinically relevant MRI and PET imaging techniques and demonstrate efficacy in restoration of motor function with a potency comparable to that seen with human fetal dopamine neurons. Furthermore, we show that hESC-derived dopamine neurons can project sufficiently long distances for use in humans, fully regenerate midbrain-to-forebrain projections, and innervate correct target structures. This provides strong preclinical support for clinical translation of hESC-derived dopamine neurons using approaches similar to those established with fetal cells for the treatment of Parkinson's disease. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Human ESC-Derived Dopamine Neurons Show Similar Preclinical Efficacy and Potency to Fetal Neurons when Grafted in a Rat Model of Parkinson’s Disease

    Science.gov (United States)

    Grealish, Shane; Diguet, Elsa; Kirkeby, Agnete; Mattsson, Bengt; Heuer, Andreas; Bramoulle, Yann; Van Camp, Nadja; Perrier, Anselme L.; Hantraye, Philippe; Björklund, Anders; Parmar, Malin

    2014-01-01

    Summary Considerable progress has been made in generating fully functional and transplantable dopamine neurons from human embryonic stem cells (hESCs). Before these cells can be used for cell replacement therapy in Parkinson’s disease (PD), it is important to verify their functional properties and efficacy in animal models. Here we provide a comprehensive preclinical assessment of hESC-derived midbrain dopamine neurons in a rat model of PD. We show long-term survival and functionality using clinically relevant MRI and PET imaging techniques and demonstrate efficacy in restoration of motor function with a potency comparable to that seen with human fetal dopamine neurons. Furthermore, we show that hESC-derived dopamine neurons can project sufficiently long distances for use in humans, fully regenerate midbrain-to-forebrain projections, and innervate correct target structures. This provides strong preclinical support for clinical translation of hESC-derived dopamine neurons using approaches similar to those established with fetal cells for the treatment of Parkinson’s disease. PMID:25517469

  13. Murine Asb-17 expression during mouse testis development and spermatogenesis.

    Science.gov (United States)

    Kim, Kye-Seong; Kim, Myung-Sun; Kim, Soo-Kyung; Baek, Kwang-Hyun

    2004-05-01

    In this study we isolated a murine mAsb-17 from mouse testis by RT-PCR using primers designed based on the sequences from the GenBank database. The sequence analysis showed that mAsb-17 encodes a 295 amino acid polypeptide with a molecular weight of approximately 34 kDa containing two ankyrin repeats and one SOCS box. The amino acid sequence of mASB-17 showed 87.5%, 98.3% and 92.9% identity with that of human, rat and dog, respectively. Interestingly, northern blot analysis showed that mAsb-17 was expressed only in the testis. The expression analysis by RT-PCR for mAsb-17 in mouse indicates that mAsb-17 is expressed from the fourth week after birth to adult, with the highest expression in round spermatids. Both northern blot and RT-PCR analyses suggest that mASB-17 may play essential roles in testis development and spermatogenesis.

  14. Retinoic Acid signalling and the control of meiotic entry in the human fetal gonad.

    Directory of Open Access Journals (Sweden)

    Andrew J Childs

    Full Text Available The development of mammalian fetal germ cells along oogenic or spermatogenic fate trajectories is dictated by signals from the surrounding gonadal environment. Germ cells in the fetal testis enter mitotic arrest, whilst those in the fetal ovary undergo sex-specific entry into meiosis, the initiation of which is thought to be mediated by selective exposure of fetal ovarian germ cells to mesonephros-derived retinoic acid (RA. Aspects of this model are hard to reconcile with the spatiotemporal pattern of germ cell differentiation in the human fetal ovary, however. We have therefore examined the expression of components of the RA synthesis, metabolism and signalling pathways, and their downstream effectors and inhibitors in germ cells around the time of the initiation of meiosis in the human fetal gonad. Expression of the three RA-synthesising enzymes, ALDH1A1, 2 and 3 in the fetal ovary and testis was equal to or greater than that in the mesonephros at 8-9 weeks gestation, indicating an intrinsic capacity within the gonad to synthesise RA. Using immunohistochemistry to detect RA receptors RARα, β and RXRα, we find germ cells to be the predominant target of RA signalling in the fetal human ovary, but also reveal widespread receptor nuclear localization indicative of signalling in the testis, suggesting that human fetal testicular germ cells are not efficiently shielded from RA by the action of the RA-metabolising enzyme CYP26B1. Consistent with this, expression of CYP26B1 was greater in the human fetal ovary than testis, although the sexually-dimorphic expression patterns of the germ cell-intrinsic regulators of meiotic initiation, STRA8 and NANOS2, appear conserved. Finally, we demonstrate that RA induces a two-fold increase in STRA8 expression in cultures of human fetal testis, but is not sufficient to cause widespread meiosis-associated gene expression. Together, these data indicate that while local production of RA within the fetal ovary may

  15. Treatment options for carcinoma in situ testis

    DEFF Research Database (Denmark)

    Mortensen, M S; Gundgaard, M.G.; Daugaard, G

    2011-01-01

    Carcinoma in situ testis (CIS) is known as the precursor of germ cell cancer of the testis. International guidelines on diagnosis and treatment are inconsistent. Some countries offer routine biopsies of the contralateral testicle in relation to orchidectomy for testicular cancer, whereas other...

  16. Comparative study of the effects of pre and post natal administration of a thyroid drug on testicular activity in adult rat.

    Directory of Open Access Journals (Sweden)

    F Hadj-Bekkouche

    2008-04-01

    Full Text Available Thyroid hormone is known to play a critical role in growth and development of rat testes with a specific effect on the differentiation of Sertoli cells leading to a normal evolution of germ cells. In the present study, we aimed to compare the effect of induced hypothyroidism during fetal and post-natal life on the structure and function of the testis in adult. Pregnant or lactating mothers were treated with 6-propyl-2-thiouracil (PTU during 21 days and weight gain of pups was steady until adult age. Plasma hormonal levels were determined by RIA and morphology of testis was studied on sections stained with Masson's trichrome. Pre and early post natal hypothyroidism resulted in an impairment of body development and a diminution of thyroid hormone levels of treated rats. No significant effect on testicular development has been observed when hypothyroidism is induced in fetal life while it was associated with reduction in testis weight, diameter of seminiferous tubules and hormonal levels and delay in maturation of germ cells, when induced during early post natal life.

  17. In vivo study on the effects of microcystin extracts on the expression profiles of proto-oncogenes (c-fos, c-jun and c-myc) in liver, kidney and testis of male Wistar rats injected i.v. with toxins.

    Science.gov (United States)

    Li, Huiying; Xie, Ping; Li, Guangyu; Hao, Le; Xiong, Qian

    2009-01-01

    Microcystins (MCs) are a potent liver tumor promoter, possessing potent tumor-promoting activity and weak initiating activity. Proto-oncogenes are known to be involved in the tumor-promoting mechanisms of microcystin-LR. However, few data are available on the effects of MCs on proto-oncogenes in the whole animal. To investigate the effects of MCs on the expression profile of the proto-oncogenes in different organs, male Wistar rats were injected intravenously with microcystin extracts at a dose of 86.7 mug MC-LR eq/kg bw (MC-LR eq, MC-LR equivalents). mRNA levels of three proto-oncogenes c-fos, c-jun and c-myc in liver, kidney and testis were analyzed using quantitative real-time PCR at several time points post-injection. Significant induction of these genes at transcriptional level was observed in the three organs. In addition, the increase of mRNA expression of all three genes was much higher in liver than in kidney and testis. Meanwhile, the protein levels of c-Fos and c-Jun were investigated by western blotting. Both proteins were induced in the three organs. However, elevations of protein levels were much lower than those of mRNA levels. These findings suggest that the expression of c-fos, c-jun and c-myc might be one possible mechanism for the tumor-promoting activity and initiating activity of microcystins.

  18. [Effect of antepartum taurine supplementation in regulating the activity of Rho family factors and promoting the proliferation of neural stem cells in neonatal rats with fetal growth restriction].

    Science.gov (United States)

    Li, Xiang-Wen; Li, Fang; Liu, Jing; Wang, Yan; Fu, Wei

    2016-11-01

    To study the possible effect of antepartum taurine supplementation in regulating the activity of Rho family factors and promoting the proliferation of neural stem cells in neonatal rats with fetal growth restriction (FGR), and to provide a basis for antepartum taurine supplementation to promote brain development in children with FGR. A total of 24 pregnant Sprague-Dawley rats were randomly divided into three groups: control, FGR, and taurine (n=8 each ). A rat model of FGR was established by food restriction throughout pregnancy. RT-PCR, immunohistochemistry, and Western blot were used to measure the expression of the specific intracellular markers for neural stem cells fatty acid binding protein 7 (FABP7), Rho-associated coiled-coil containing protein kinase 2 (ROCK2), ras homolog gene family, member A (RhoA), and Ras-related C3 botulinum toxin substrate (Rac). The FGR group had significantly lower OD value of FABP7-positive cells and mRNA and protein expression of FABP7 than the control group, and the taurine group had significantly higher OD value of FABP7-positive cells and mRNA and protein expression of FABP7 than the FGR group (Ptaurine group had significantly higher mRNA expression of RhoA and ROCK2 than the control group and significantly lower expression than the FGR group (Ptaurine group had significantly higher mRNA expression of Rac than the FGR and control groups (Ptaurine group had significantly lower protein expression of RhoA and ROCK2 than the FGR group (Ptaurine supplementation can promote the proliferation of neural stem cells in rats with FGR, and its mechanism may be related to the regulation of the activity of Rho family factors.

  19. Tracer kinetic studies of the low density lipoprotein metabolism in the fetal rat: An example for estimation of flux rates in the nonsteady state

    Energy Technology Data Exchange (ETDEWEB)

    Plonne, D.; Schlag, B.; Winkler, L.; Dargel, R. (Friedrich Schiller Univ., Jena (German Democratic Republic))

    1990-05-01

    To get insight into the low density lipoprotein (LDL)-apoB flux in the rat fetus near term and in the early postnatal period, homologous apoE-free 125I-labeled LDL was injected into the umbilical vein of the rat fetus immediately after Caesarean section. Since the serum LDL-apoB spontaneously declined after birth, a time-dependent two-pool model was used to calculate the flux rates in the neonate from the specific activities of LDL-apoB up to 15 h post partum. An approximate value of LDL-apoB flux in the fetus at birth was obtained by extrapolation of the kinetic data to the time of injection of the tracer. The data revealed that the turnover of LDL-apoB in the fetus (18.6 micrograms LDL-apoB/h per g body weight) exceeded that in the adult rat (0.4 microgram/h per g body weight) by at least one order of magnitude. Even 15 h after delivery, the LDL-apoB influx amounted to 2.5 micrograms/h per g body weight. The fractional catabolic rate of LDL-apoB in the fetus at term (0.39, h-1) slightly exceeded that in the adult animal (0.15, h-1) and reached the adult level within the first 3 h after birth and remained constant thereafter. In the rat fetus, LDL-apoB flux greatly exceeds that of VLDL-apoB. The data support the view of a direct synthesis and secretion of LDL, most probably by the fetal membranes.

  20. Identification and Characteristics of a Novel E1 Like Gene nUBE1L in Human Testis

    Institute of Scientific and Technical Information of China (English)

    Hui ZHU; Jia-Hao SHA; Zuo-Min ZHOU; Ran HUO; Xiao-Yan HUANG; Li LU; Min LIN; Li-Rong WANG; Ya-Dong ZHOU; Jian-Min LI

    2004-01-01

    A gene,presumably involved in spermatogenesis,was identified and characterized by using cDNA microarray.Hybridization intensity was 2.13 fold higher in adult testis than that in fetal testis.The full length of this gene was 4288 bp and it encoded a 578 amino acid protein.Conserved structure and amino acid sequence analysis revealed that the protein contained 1 Thif-domain,2 UBACT-domains,and a functional active site cysteine lay upstream of UBACT domain,all of them also existed in ubiquitinactivating enzyme E1 and E1 like proteins.So we named this gene as a novel ubiquitin-activating enzyme E1 like gene(nUBE1L).Expression profile showed that nUBEIL was predominantly expressed in testis.Comparison of the expression of nUBE1L in different developmental stages of testis indicated that it was highly expressed in adult testis.In conclusion,nUBE1L is a novel human E1 like gene highly expressed in adult testis,which plays key role in ubiquitin system,and accordingly influences spermatogenesis and male fertility.

  1. Purification of fetal liver stem/progenitor cells containing all the repopulation potential for normal adult rat liver

    DEFF Research Database (Denmark)

    Oertel, Michael; Menthena, Anuradha; Chen, Yuan-Qing

    2008-01-01

    and characteristic properties in vitro and their proliferative and differentiation potential in vivo after transplantation into normal adult rat liver. RESULTS: Rat ED14 FLSPC were purified to 95% homogeneity and exhibited cell culture and gene expression characteristics expected for hepatic stem/progenitor cells...

  2. Fetal Macrosomia

    Science.gov (United States)

    ... might need special care in the hospital's neonatal intensive care unit. Keep in mind that your baby might ... References Copel JA, et al. Fetal macrosomia. In: Obstetric Imaging. Philadelphia, Pa.: Saunders Elsevier; 2012. http://www. ...

  3. Fetal Ultrasound

    Science.gov (United States)

    ... needle placement during certain prenatal tests, such as amniocentesis or chorionic villus sampling. Determine fetal position before ... home. Accessed Aug. 11, 2015. Ghidini A. Diagnostic amniocentesis. http://www.uptodate.com/home. Accessed Aug. 11, ...

  4. Fetal pain

    OpenAIRE

    Adama van Scheltema, Phebe

    2011-01-01

    Recent studies have suggested that the fetus is capable of exhibiting a stress response to intrauterine needling, resulting in alterations in fetal stress hormone levels. Intrauterine transfusions are performed by inserting a needle either in the umbilical cord root at the placental surface (PCI), or in the intrahepatic portion of the umbilical vein (IHV). Aim of our study was to test the hypothesis that fetal hormonal changes during intrauterine transfusion are more pronounced when the needl...

  5. Electroacupuncture atBaihui (DU20) acupoint up-regulates mRNA expression of NeuroD molecules in the brains of newborn rats sufferingin utero fetal distress

    Institute of Scientific and Technical Information of China (English)

    Lu Chen; Yan Liu; Qiao-mei Lin; Lan Xue; Wei Wang; Jian-wen Xu

    2016-01-01

    NeuroD plays a key regulatory effect on differentiation of neural stem cells into mature neurons in the brain. Thus, we assumed that electroacupuncture atBaihui (DU20) acupoint in newborn rats exposed toin utero fetal distress would inlfuence expression of NeuroD. Electroacupuncture atBaihui was performed for 20 minutes on 3-day-old (Day 3) newborn Sprague-Dawley rats exposed toin utero fetal distress; electroacupuncture parameters consisted of sparse and dense waves at a frequency of 2–10 Hz. Real-time lfuorescent quantitative PCR results demonstrated that mRNA expression of NeuroD, a molecule that indicates NeuroD, increased with prolonged time in brains of newborn rats, and peaked on Day 22. The level of mRNA expression was similar between Day 16 and Day 35. These ifndings suggest that electro acupuncture atBaihui acupoint could effectively increase mRNA expression of molecules involved in NeuroD in the brains of new-born rats exposed to in utero fetal distress.

  6. [Fetal magnetocardiography].

    Science.gov (United States)

    van Leeuwen, P

    1997-09-01

    Fetal magnetocardiography is a new, alternative method for prenatal surveillance. The fetal magnetocardiogram (FMCG) registers the magnetic field produced by conduction currents in the fetal heart. Compared to the fetal electrocardiogram, the propagation of magnetic fields is relatively undisturbed by surrounding tissue. The FMCG thus has the advantage of a higher signal-to-noise ratio and can be acquired earlier pregnancy. Also, the high temporal resolution of the signal permits a significantly more precise determination of fetal heart rate parameters than fetal ultrasound. FMCG registration using a biomagnetometer is noninvasive and can be performed as of the second trimeter. It can be used to examine signal morphology, cardiac time intervals, heart rate variability as well as cardiac magnetic fields. To date, arrhythmic activity has been observed in the form of supraventricular and ventricular ectopies as well as atrial flutter, atrio-ventricular block, atrial tachycardia and Torsades de Pointes tachycardia. We also report here on the presence of short episodes of bradycardia in the second trimester of normal pregnancy. Measurement of the magnetic field strength at various locations above the abdomen has allowed the reconstruction of the fetal cardiac magnetic field and the determination of its relation to the position of the fetus. Signal averaging has permitted the precise examination of signal amplitude and cardiac time intervals and has shown that they increase in the course of pregnancy. Heart rate variability could be quantified in the time and frequency domain as well as using parameters of nonlinear dynamics. The results demonstrated an increase of variability and complexity over gestational age. Furthermore spectral analysis of fetal heart arte data could be associated with sympathetic and parasympathetic activity as well as, with respiration. Although the studies presenting these results have involved only limited numbers of observations, they

  7. Transplantation of fetal liver tissue suspension into the spleens of adult syngenic rats: inducibility of cytochrome P450 dependent monooxygenase functions by beta-naphthoflavone, phenobarbital and dexamethasone.

    Science.gov (United States)

    Lupp, A; Lau, K; Trautmann, A K; Krausse, T; Klinger, W

    1999-01-01

    In the present study the effects of beta-naphthoflavone (BNF), phenobarbital (PB) and dexamethasone (DEX) on cytochrome P450 (P450) dependent monooxygenase functions were investigated in intrasplenic liver cell explants in comparison to adult liver. Fetal liver tissue suspensions were transplanted into the spleens of 60-90 days old adult male syngenic Fisher 344 inbred rats. 2, 4 or 6 months after surgery, transplant recipients and age matched controls were orally treated with BNF (1x50 mg/kg body weight (b.wt.)), PB (1x50 mg/kg b.wt.), DEX (for 3 days 4 mg/kg b.wt. per day), or the respective solvents (dimethylsulfoxide or 0.9% NaCl). The animals were sacrificed 24 (BNF, DEX) or 48 (PB) hours after the last treatment. P450 mediated monooxygenase functions were measured in spleen and liver 9000 g supernatants by three model reactions for different P450 subtypes: ethoxyresorufin O-deethylation (EROD; 1A), ethoxycoumarin O-deethylation (ECOD; 1A, 2A, 2B), and ethylmorphine N-demethylation (END; 3A). Spleen weights were significantly higher in transplanted rats, compared to controls, at all three time points after surgery. Induction with PB or DEX, and in some cases also with BNF, lead to a significant increase in liver weights of transplant recipients and control rats independent of the time after transplantation. In contrast, there was no influence on spleen weights due to BNF or PB. At all time points after surgery, with DEX a marked decrease in body weights, weights of adrenal glands and of lymphatic organs like thymus glands and spleens was observed, with the weights of the transplant containing spleens being still higher in comparison to control organs. Spleens of control animals displayed nearly no P450 mediated monooxygenase functions neither without nor with induction. After transplantation, however, significant EROD and ECOD, but hardly any END activities were seen in the host organs at all three time points after surgery. In transplant containing spleens

  8. Regulation of pulmonary surfactant synthesis in fetal rat type II alveolar epithelial cells by microRNA-26a.

    Science.gov (United States)

    Zhang, Xiao-Qun; Zhang, Pan; Yang, Yang; Qiu, Jie; Kan, Qin; Liang, Hong-Lu; Zhou, Xiao-Yu; Zhou, Xiao-Guang

    2014-09-01

    Pulmonary surfactant, a unique developmentally regulated, phospholipid-rich lipoprotein, is synthesized by the type II epithelial cells (AECII) of the pulmonary alveolus, where it is stored in organelles termed lamellar bodies. The synthesis of pulmonary surfactant is under multifactorial control and is regulated by a number of hormones and factors, including glucocorticoids, prolactin, insulin, growth factors, estrogens, androgens, thyroid hormones, and catecholamines acting through beta-adrenergic receptors, and cAMP. While there is increasing evidence that microRNAs (miRNAs) are involved in the regulation of almost every cellular and physiological process, the potential role of miRNAs in the regulation of pulmonary surfactant synthesis remains unknown. miRNA-26a (miR-26a) has been predicted to target SMAD1, one of the bone morphogenetic protein (BMP) receptor downstream signaling proteins that plays a key role in differentiation of lung epithelial cells during lung development. In this study, we explored the regulation role of miR-26a in the synthesis of pulmonary surfactant. An adenoviral miR-26a overexpression vector was constructed and introduced into primary cultured fetal AECII. GFP fluorescence was observed to determinate the transfection efficiency and miR-26a levels were measured by RT-PCR. MTT was performed to analyze AECII viability. qRT-PCR and Western blotting were used to determine the mRNA and protein level of SMAD1 and surfactant-associated proteins. The results showed that miR-26a in fetal AECII was overexpressed after the transfection, and that the overexpression of miR-26a inhibited pulmonary surfactant synthesis in AECII. There was no significant change in cell proliferation. Our results further showed that overexpression of miR-26a reduced the SMAD1 expression both in mRNA and protein level in fetal AECII. These findings indicate that miR-26a regulates surfactant synthesis in fetal AECII through SMAD1.

  9. Epidemiology and Diagnosis of Testis Cancer.

    Science.gov (United States)

    Stevenson, Scott M; Lowrance, William T

    2015-08-01

    Testis cancer is the most commonly diagnosed cancer in young men. Most cases represent sporadic occurrences. Most commonly it presents at an early stage (clinical stage I) and is highly curable with radical orchiectomy. Even more advanced stages of testicular cancer are curable with a multimodality treatment approach. There are no widely accepted screening strategies for germ cell tumors. This article discusses the known risk factors and epidemiology of testis cancer, the presentation, and work up for new patients, and the prognosis and cure rates based on the staging and current treatment modalities for testis cancer patients.

  10. Selenium-vitamin E combination and melatonin modulates diabetes-induced blood oxidative damage and fetal outcomes in pregnant rats.

    Science.gov (United States)

    Guney, Mehmet; Erdemoglu, Evrim; Mungan, Tamer

    2011-11-01

    Oxidative stress is considered to be the main cause of diabetic complications. In the current study, we investigated the effect of selenium-vitamin E combination and melatonin on lipid peroxidation (LPO) and scavenging enzyme activity in the blood of streptozocin (STZ)-induced diabetic pregnant rats. Forty female Wistar rats were randomly divided into five groups. The first and second groups were used as the non-pregnant control and pregnant control groups, respectively. The third group was the pregnant diabetic group. Vitamin E plus selenium and melatonin were administered to the diabetic pregnant rats consisting fourth and fifth groups, respectively. Diabetes was induced on day 0 of the study by STZ. Blood samples were taken from all animals on the 20th day of pregnancy. LPO level was higher in diabetic pregnant rats than in control, although superoxide dismutase, catalase, and glutathione peroxidase activities were lower in diabetic pregnant animals than in control. LPO levels were lower both in the two treatment groups than in the diabetic pregnant rats, whereas selenium-vitamin E combination and melatonin caused a significant increase in the activities of these antioxidant enzymes (pmelatonin in diabetic pregnant rats. Melatonin did not significantly affect the elevated glucose concentration of diabetic pregnant treated with melatonin group. Vitamin E plus selenium may play a role in preventing diabetes-related diseases of pregnant subjects.

  11. Morphological and functional aspects of acute kidney injury after fetal programing in the offspring of diabetic rats.

    Science.gov (United States)

    Pucci, Karla Roberta Martins; Pereira Júnior, Carlos Donizete; Idaló, Priscila Barbosa; Moreira, Ana Carolina Santana Pinheiro; Rocha, Laura Penna; Rodrigues, Aldo Rogélis Aquiles; Reis, Luiz Carlos Dos; Gomes, Roseli A da Silva; Rocha, Lenaldo Branco; Guimarães, Camila Souza de Oliveira; Reis, Marlene Antônia Dos; Câmara, Niels Olsen Saraiva; Corrêa, Rosana Rosa Miranda

    2015-03-01

    To evaluate the effects of folic acid (FA)-induced renal failure in young offspring of diabetic mothers. The offspring of streptozotocin-induced diabetic dams were divided into four groups: CC (controls receiving vehicle); DC (diabetics receiving vehicle); CA (controls receiving FA solution, 250 mg/kg) and DA (diabetics receiving FA solution, 250 mg/kg). Renal function tests and morphometry results were analyzed. An increase in creatinine and urea levels was observed in CA and DA groups at two and five months. FA administration caused a significant reduction in the number of glomeruli in the offspring of diabetic dams. The diabetes group treated with FA had fewer glomeruli compared to controls at two and five months. FA caused an increase in the area of the urinary space both in controls and offspring of diabetic dams at two and five months. The number of glomeruli and area of the urinary space at two months were negatively correlated. Fetal programing promotes remarkable changes in kidney morphology and function in offspring. We suggest that the morphological changes in the kidneys are more pronounced when fetal programing is associated with newly acquired diseases, e.g. renal failure induced by FA.

  12. Development of the insulin secretion mechanism in fetal and neonatal rat pancreatic B-cells: response to glucose, K+, theophylline, and carbamylcholine

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    A.C. Mendonça

    1998-06-01

    Full Text Available We studied the development of the insulin secretion mechanism in the pancreas of fetal (19- and 21-day-old, neonatal (3-day-old, and adult (90-day-old rats in response to stimulation with 8.3 or 16.7 mM glucose, 30 mM K+, 5 mM theophylline (Theo and 200 µM carbamylcholine (Cch. No effect of glucose or high K+ was observed on the pancreas from 19-day-old fetuses, whereas Theo and Cch significantly increased insulin secretion at this age (82 and 127% above basal levels, respectively. High K+ also failed to alter the insulin secretion in the pancreas from 21-day-old fetuses, whereas 8.3 mM and 16.7 mM glucose significantly stimulated insulin release by 41 and 54% above basal levels, respectively. Similar results were obtained with Theo and Cch. A more marked effect of glucose on insulin secretion was observed in the pancreas of 3-day-old rats, reaching 84 and 179% above basal levels with 8.3 mM and 16.7 mM glucose, respectively. At this age, both Theo and Cch increased insulin secretion to close to two-times basal levels. In islets from adult rats, 8.3 mM and 16.7 mM glucose, Theo, and Cch increased the insulin release by 104, 193, 318 and 396% above basal levels, respectively. These data indicate that pancreatic B-cells from 19-day-old fetuses were already sensitive to stimuli that use either cAMP or IP3 and DAG as second messengers, but insensitive to stimuli such as glucose and high K+ that induce membrane depolarization. The greater effect of glucose on insulin secretion during the neonatal period indicates that this period is crucial for the maturation of the glucose-sensing mechanism in B-cells.

  13. Study on the expression of annexin 5 in rat testis under acute pain stress%急性疼痛应激状态下SD大鼠睾丸内膜联蛋白A5的表达变化

    Institute of Scientific and Technical Information of China (English)

    韩雪峰; 卢坤刚; 张艳梅; 时姗姗; 柳海燕; 陶晓倩; 姚兵

    2009-01-01

    目的 观察急性疼痛应激状态下,睾丸中annexin 5表达变化.方法 福尔马林注射建立急性疼痛模型,分别在注射后1 h,6 h,24 h,72 h取睾丸,免疫组织化学和western b10t分析annexin 5免疫定位和蛋向表达,荧光定量PCR方法检测annexin 5 mRNA水平变化.结果 免疫组化显示,annexin 5在急性应激组和对照组中定位在间质细胞、支持细胞,应激组与对照组相比定位无明显的变化.Westem b1ot分析发现疼痛应激1 h和6 h后,annexin 5的表达分别降低16.9%和12.8%,而在疼痛应激24 h和72 h后,annexin 5的表达分别升高33.7%和25%.组间比较发现,在l h和24 h时annexjn 5表达较对照组差异有统计学意义(P<0.05).荧光定量方法检测annexin 5 mRNA水平变化,发现疼痛应激1h和6 h annexin 5 mRNA相对含量降低,随后在24 h和72 h升高,但各组间差异均无统计学意义.结论 急性疼痛应激主要影响annexin 5蛋白的表达,而不影响annexin 5的转录.Annexin 5作为睾丸应激因子之一可能介导了应激对生殖功能的抑制作用.%Objective To study on the expression of annexin 5 expression in rat testis under acute pain stress. Methods SD rat models with acute pain stress were established by injection of formalin, and their testis were collected respectively at 1 h ,6 h ,24 h and 72 h after injection. The distribution and expression of annexin 3 protein were detected by Immunohistochemistry and western blot. The level of annexin 5 mRNA was measured by quantitative RT-PCR. Results Immunohistochemistry staining showed that annexin 5 was mainly distributed in Sertoli cell and Leydig cells of rat testis. Analysis of western blot exhibited that the expression of annexin 5 decreased about 16.9 % and 12. 8% respectively at lh and 6h after injection of formalin, whereas increased 33.7% and 25% at 24 h and 72 h after injecting formalin. Compared with that of control group, statistical difference were found in the expression of annexin 5 at

  14. Seminoma in the testis presenting as hemospermia

    DEFF Research Database (Denmark)

    Beji, Sami; Hoejgaard, Martin; Lyngdorf, Peter

    2012-01-01

    Hemospermia is often considered idiopathic. We report a case of a patient who presented with hemospermia. Scrotal examination and ultrasonography found a testis tumor. This case underscores the importance of scrotal examination and eventually ultrasound in patients presenting with hemospermia....

  15. Molecular cloning of a novel nuclear factor, TDRP1, in spermatogenic cells of testis and its relationship with spermatogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xuanchun [Department of Endocrinology, Huashan Hospital, Institute of Endocrinology and Diabetology at Fudan University, Shanghai Medical College, Fudan University, Shanghai 200040 (China); Jiang, Haowen [Department of Urology, Huashan Hospital, Institute of Urology at Fudan University, Shanghai Medical College, Fudan University, Shanghai 200040 (China); Zhou, Wenbai; Zhang, Zhaoyun; Yang, Zhihong [Department of Endocrinology, Huashan Hospital, Institute of Endocrinology and Diabetology at Fudan University, Shanghai Medical College, Fudan University, Shanghai 200040 (China); Lu, Yong [Department of Urology, Huashan Hospital, Institute of Urology at Fudan University, Shanghai Medical College, Fudan University, Shanghai 200040 (China); Lu, Bin [Department of Endocrinology, Huashan Hospital, Institute of Endocrinology and Diabetology at Fudan University, Shanghai Medical College, Fudan University, Shanghai 200040 (China); Wang, Xiang [Department of Urology, Huashan Hospital, Institute of Urology at Fudan University, Shanghai Medical College, Fudan University, Shanghai 200040 (China); Ding, Qiang, E-mail: dingqiangd@hotmail.com [Department of Urology, Huashan Hospital, Institute of Urology at Fudan University, Shanghai Medical College, Fudan University, Shanghai 200040 (China); Hu, Renming, E-mail: renminghu@fudan.edu.cn [Department of Endocrinology, Huashan Hospital, Institute of Endocrinology and Diabetology at Fudan University, Shanghai Medical College, Fudan University, Shanghai 200040 (China)

    2010-03-26

    We reported the identification of a novel gene termed TDRP (encoding testis development-related protein) that might be involved in spermatogenesis. The human TDRP gene had two distinct transcripts, TDRP1 and TDRP2, which encoded proteins of 183 aa and 198 aa respectively. Tdrp mRNA was predominantly expressed in testis tissue. We generated rabbit polyclonal antibodies specific against human TDRP1. Immunohistochemistry analysis showed TDRP1 was expressed in spermatogenic cells, especially with high expression in spermatocytes. We provided evidence that TDRP1 distributed in both cytoplasm and nuclei of spermatogenic cells. Expression patterns of Tdrp1 mRNA and its protein were investigated in the rat testis tissues of different developmental stages. Both Tdrp1 mRNA and its protein were barely detected in the testis of neonatal rats, increased remarkably at 3 weeks postpartum, and peaked at 2 months postpartum. We also investigated TDRP1 expressions in testis tissues of azoospermic men with defective spermatogenesis. Western blot analysis showed that TDRP1 expressions were significantly lower in the testis tissues of azoospermic men compared with normal controls. These current data demonstrated that as a nuclear factor, TDRP1 might play an important role in spermatogenesis.

  16. UNDESCENDED TESTIS, DIAGNOSIS AND TREATMENT

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    Winarta Lesmana Handrea

    2013-05-01

    Full Text Available Normal 0 false false false EN-US X-NONE X-NONE Undescended testis (UDT or cryptorchidism is one of the commonest abnormalities in male infants. In this anomaly, testes are not located normally in the scrotum. The incidence of UDT is 4-5% of term male infants, and 20-33% of premature male infants. The occurrence of abnormalities of hormones control or anatomy process that is required in the normal process of lowering the testes can cause UDT. UDT can be differentiated into palpable and nonpalpable. The diagnosis of UDT can be known through physical examination. However, if the testes are impalpable, laparoscopy can be done to determine the position of the testis. Hormonal therapy to overcome UDT is still under controversy. The action that often done is surgery, called orchidopexy. The most serious complication of orchidopexy is testicular atrophy. It occurs in a small percentage, which is about 5-10%. Infertility may occur in 1 to 3 of 4 adult males and the risk of occurrence of malignancies is increased by as much as 5-10 times higher in men with a history of UDT. /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin-top:0in; mso-para-margin-right:0in; mso-para-margin-bottom:10.0pt; mso-para-margin-left:0in; line-height:115%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

  17. Metastasis of Prostate Adenocarcinoma to the Testis

    Science.gov (United States)

    Campara, Zoran; Simic, Dejan; Aleksic, Predrag; Spasic, Aleksandar; Milicevic, Snjezana

    2016-01-01

    Introduction: Prostate carcinoma is the most frequently diagnosed carcinoma in the male population. The most typical places of the metastases are pelvic lymphatic glands, bones and lungs, and very rarely it metastasizes into a testis. The prognostic importance of testicular metastasis of prostate cancer is not yet well-known, due to a very few published cases. According to the known facts, it is certain that a metastasis of the prostate carcinoma into a testis is a sign of an advanced disease. Case report: This work presents a 48-year-old patient, to whom an adenocarcinoma of the prostate has been proven by the pathohistological finding of transrectal biopsy, performed due to the elevated level of prostate-specific antigen (PSA). Nine years after the initial diagnosis, due to a gradual rise of PSA and tumorous enlargement of the left testis, left inguinal orchectomy and right orchectomy were performed. Metastatic dissemination of prostate adenocarcinoma into a testis was determined by a pathohistological analysis of the left testis. Conclusion: The metastasis of the prostate carcinoma into a testis, as a rare localization of the metastatic dissemination, after additionally performed orchectomy along with further oncological therapy, can provide a continuation of a good life quality as well as a control of the disease in a longer time period. PMID:27703299

  18. Mitochondrial Respiration Is Decreased in Rat Kidney Following Fetal Exposure to a Maternal Low-Protein Diet

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    Sarah Engeham

    2012-01-01

    Full Text Available Maternal protein restriction in rat pregnancy is associated with impaired renal development and age-related loss of renal function in the resulting offspring. Pregnant rats were fed either control or low-protein (LP diets, and kidneys from their male offspring were collected at 4, 13, or 16 weeks of age. Mitochondrial state 3 and state 4 respiratory rates were decreased by a third in the LP exposed adults. The reduction in mitochondrial function was not explained by complex IV deficiency or altered expression of the complex I subunits that are typically associated with mitochondrial dysfunction. Similarly, there was no evidence that LP-exposure resulted in greater oxidative damage to the kidney, differential expression of ATP synthetase β-subunit, and ATP-ADP translocase 1. mRNA expression of uncoupling protein 2 was increased in adult rats exposed to LP in utero, but there was no evidence of differential expression at the protein level. Exposure to maternal undernutrition is associated with a decrease in mitochondrial respiration in kidneys of adult rats. In the absence of gross disturbances in respiratory chain protein expression, programming of coupling efficiency may explain the long-term impact of the maternal diet.

  19. Spreading the clinical window for diagnosing fetal-onset hypogonadism in boys

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    Rodolfo eRey

    2014-05-01

    Full Text Available In early fetal development, the testis secretes –independently of pituitary gonadotropins– androgens and anti-Müllerian hormone (AMH which are essential for male sex differentiation. In the second half of fetal life, the hypothalamic-pituitary axis gains control of testicular hormone secretion. FSH controls Sertoli cell proliferation, responsible for testis volume increase and AMH and inhibin B secretion, whereas LH regulates Leydig cell androgen and INSL3 secretion, involved in the growth and trophism of male external genitalia and in testis descent. This differential regulation of testicular function between early and late fetal periods underlies the distinct clinical presentations of fetal-onset hypogonadism in the newborn male: primary hypogonadism results in ambiguous or female genitalia when early fetal-onset whereas it becomes clinically undistinguishable from central hypogonadism when established later in fetal life. The assessment of the hypothalamic-pituitary-gonadal axis in the male has classically relied on the measurement of gonadotropin and testosterone levels in serum. These hormone levels normally decline 3-6 months after birth, thus constraining the clinical evaluation window for diagnosing male hypogonadism. The advent of new markers of gonadal function has spread this clinical window beyond the first 6 months of life. In this review, we discuss the advantages and limitations of old and new markers used for the functional assessment of the hypothalamic-pituitary-testicular axis in boys suspected of fetal-onset hypogonadism.

  20. Fetal pain

    NARCIS (Netherlands)

    Adama van Scheltema, Phebe

    2011-01-01

    Recent studies have suggested that the fetus is capable of exhibiting a stress response to intrauterine needling, resulting in alterations in fetal stress hormone levels. Intrauterine transfusions are performed by inserting a needle either in the umbilical cord root at the placental surface (PCI), o

  1. Alterations in male rats following in utero exposure to betamethasone suggests changes in reproductive programming.

    Science.gov (United States)

    Borges, Cibele S; Dias, Ana Flávia M G; Rosa, Josiane Lima; Silva, Patricia V; Silva, Raquel F; Barros, Aline L; Sanabria, Marciana; Guerra, Marina T; Gregory, Mary; Cyr, Daniel G; De G Kempinas, Wilma

    2016-08-01

    Antenatal betamethasone is used for accelerating fetal lung maturation for women at risk of preterm birth. Altered sperm parameters were reported in adult rats after intrauterine exposure to betamethasone. In this study, male rat offspring were assessed for reproductive development after dam exposure to betamethasone (0.1mg/kg) or vehicle on Days 12, 13, 18 and 19 of pregnancy. The treatment resulted in reduction in the offspring body weight, delay in preputial separation, decreased seminal vesicle weight, testosterone levels and fertility, and increased testicular weight. In the testis, morphologically abnormal seminiferous tubules were observed, characterized by an irregular cell distribution with Sertoli cell that were displaced towards the tubular lumen. These cells expressed both Connexin 43 (Cx43) and Proliferative Nuclear Cell Antigen (PCNA). In conclusion, intrauterine betamethasone treatment appears to promote reproductive programming and impairment of rat sexual development and fertility due to, at least in part, unusual testicular disorders.

  2. Maternal iron deficiency worsens the associative learning deficits and hippocampal and cerebellar losses in a rat model of fetal alcohol spectrum disorders.

    Science.gov (United States)

    Huebner, Shane M; Tran, Tuan D; Rufer, Echoleah S; Crump, Peter M; Smith, Susan M

    2015-11-01

    Gestational alcohol exposure causes lifelong physical and neurocognitive deficits collectively referred to as fetal alcohol spectrum disorders (FASDs). Micronutrient deficiencies are common in pregnancies of alcohol-abusing women. Here we show the most common micronutrient deficiency of pregnancy-iron deficiency without anemia-significantly worsens neurocognitive outcomes following perinatal alcohol exposure. Pregnant rats were fed iron-deficient (ID) or iron-sufficient diets from gestational day 13 to postnatal day (P) 7. Pups received alcohol (0, 3.5, 5.0 g/kg) from P 4 to P 9, targeting the brain growth spurt. At P 32, learning was assessed using delay or trace eyeblink classical conditioning (ECC). Cerebellar interpositus nucleus (IPN) and hippocampal CA1 cellularity was quantified using unbiased stereology. Global analysis of variance revealed that ID and alcohol separately and significantly reduced ECC learning with respect to amplitude (ps ≤ 0.001) and conditioned response [CR] percentage (ps ≤ 0.001). Iron and alcohol interacted to reduce CR percentage in the trace ECC task (p = 0.013). Both ID and alcohol significantly reduced IPN (ps learning impairments persisted even though the offsprings' iron status had normalized. Supporting our previous work, gestational ID exacerbates the associative learning deficits in this rat model of FASD. This is strongly associated with cellular reductions within the ECC neurocircuitry. Significant learning impairments in FASD could be the consequence, in part, of pregnancies in which the mother was also iron inadequate. Copyright © 2015 by the Research Society on Alcoholism.

  3. De verworven niet-scrotale testis bij jongens: Een onderschat fenomeen [Acquired undescended testis in boys

    NARCIS (Netherlands)

    Hack, W.W.M.; Hirasing, R.A.

    1996-01-01

    Objective. To differentiate undescended testis into a congenital and an acquired form using earlier information on testis position. Design. Descriptive. Setting. Paediatric outpatients' clinic, Medical Centre Alkmaar, the Netherlands. Method. In a 3-year period (1991-1994), 77 boys were referred to

  4. Effects of lead on ultrastructural charactristics of sinusoidal endothelial cell of fetal rat's spleen

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    Heydari Z

    1997-08-01

    Full Text Available Amount of environmental lead pollution is increased with progression of industry. This pollution is able to damage the living beings in many ways. Blood and Immune systems are more sensitive to toxic effects of lead. 30 female and 6 male rats from Sprague dawley race are chosen by simple random sampling. After copulation and vaginal plug observation, expectant rats are calssified in test and control groups. Since the first day of pregnancy, test group is given a drink containing lead acetate 0.13% in distilled water and control group is given distilled water. After delivery, for ultrastrectural studies, spleen specimens of newborn rats are fixed in glutaraldehyde solution 2% and after processing are studied by T.E.M. Sinusoidal endothelial cell show: morphological changes in mitochondria, appearance of primary & secondary lysosomes and multivesicular bodies and swelling in ER. It seems that these changes are caused by interaction of lead with enzymathic functions or lead accumulation in these cellular organels.

  5. Man is not a big rat: concerns with traditional human risk assessment of phthalates based on their anti-androgenic effects observed in the rat foetus.

    Science.gov (United States)

    Habert, René; Livera, Gabriel; Rouiller-Fabre, Virginie

    2014-01-01

    Phthalates provide one of the most documented example evidencing how much we must be cautious when using the traditional paradigm based on extrapolation of experimental data from rodent studies for human health risk assessment of endocrine disruptors (EDs). Since foetal testis is known as one of the most sensitive targets of EDs, phthalate risk assessment is routinely based on the capacity of such compounds to decrease testosterone production by the testis or to impair masculinization in the rat during foetal life. In this paper, the well-established inhibiting effects of phthalates of the foetal Leydig cells function in the rat are briefly reviewed. Then, data obtained in humans and other species are carefully analysed. Already in January 2009, using the organotypic culture system named Fetal Testis Assay (FeTA) that we developed, we reported that phthalates might not affect testosterone production in human foetal testes. Several recent experimental studies using xenografts confirm the absence of detectable anti-androgenic effect of phthalates in the human foetal testes. Epidemiological studies led to contradictory results. Altogether, these findings suggest that phthalates effects on foetal Leydig cells are largely species-specific. Consequently, the phthalate threshold doses that disturb foetal steroidogenesis in rat testes and that are presently used to define the acceptable daily intake levels for human health protection must be questioned. This does not mean that phthalates are safe because these compounds have many deleterious effects upon germ cell development that may be common to the different studied species including human. More generally, the identification of common molecular, cellular or/and phenotypic targets in rat and human testes should precede the choice of the toxicological endpoint in rat to accurately assess the safety threshold of any ED in humans.

  6. Flunarizine and lamotngine propnyiaxis effects on neuron-specific enolase,S-100,and brain-specific creatine kinase in a fetal rat model of hypoxic-ischemic brain damage

    Institute of Scientific and Technical Information of China (English)

    Li He; Jingyi Deng; Wendan He

    2008-01-01

    BACKGROUND:Calcium antagonists may act as neuroprotectants,diminishing the influx of calcium ions through voltage-sensitive calcium channels. When administered prophylactically,they display neuroprotective effects against hypoxic-ischemic brain damage in newborn rats.OBJECTIVE:To investigate the neuroprotective effects of flunarizine(FNZ),lamotrigine (LTG)and the combination of both drugs,on hypoxic-ischemic brain damage in fetal rats.DESIGN AND SETTING:This randomized,complete block design was performed at the Department of Pediatrics.Shenzhen Fourth People's Hospital,Guangdong Medical College.MATERIALS:Forty pregnant Wistar rats,at gestational day 20,were selected for the experiment and were randomly divided into FNZ,LTG,FNZ+LTG,and model groups,with 10 rats in each group.METHODS:Rats in the FNZ.LTG,and FNZ+LTG groups received intragastric injections of FNZ (0.5 mg/kg/d),LTG(10 mg/kg/d),and FNZ(0.5 mg/kg/d)+LTG(10 mg/kg/d),respectively.Drugs were administered once a day for 3 days prior to induction of hypoxia-ischemia.Rats in the modeJ group were not administered any drugs.Three hours after the final administration,eight pregnant rats from each group underwent model establishment hypoxia-ischemia brain damage to the fetal rats.Cesareans were performed at 6,12,24,and 48 hours later;and 5 fetal rats were removed from each mother and kept warm.Twe fetuses without model establishment were removed by planned cesarean at the same time and served as controls.A total of 0.3 mL serum was collected from fetal rats at 6,12,24,and 48 hours,respectively,following birth.MAIN OUTCOME MEASURES:Serum protein concentrations of neuron-specific enolase and S-100 were measured by ELISA.Serum concentrations of brain-specific creatine kinase were measured using an electrogenerated chemiluminescence method.RESULTS:Serum concentrations of neuron-specific enolase,S-100,and brain-specific creatine kinase were significantly higher in the hypoxic-ischemic fetal rats.compared with the non

  7. An experimental model for the transplantation of fetal central nervous system cells to the injured spinal cord in rats Modelo experimental de transplante de células do sistema nervoso central fetal para lesão de medula espinal em ratos

    Directory of Open Access Journals (Sweden)

    Tarcísio Eloy Pessoa de Barros Filho

    2002-01-01

    Full Text Available INTRODUCTION: Traumatic spinal cord injury is one of the most disabling conditions occurring in man and thus stimulates a strong interest in its histopathological, biochemical, and functional changes, primarily as we search for preventive and therapeutic methods. PURPOSE: To develop an experimental model for transplantation of cells from the fetal rat central nervous system to the site of an injured spinal cord of an adult rat in which the transplanted cells survive and become integrated. This experimental model will facilitate investigations of factors that promote regeneration and functional recovery after spinal cord trauma. MATERIAL AND METHODS: Fifteen adult Wistar rats underwent laminectomy, and an spinal cord lesion was made with microdissection. Fetal spinal cord tissue was then transplanted to the site of the injury. The rats were monitored over a 48-hour period, and then their vertebral column was completely removed for histological analysis. RESULTS: In 60% of transplanted rats, the fetal tissue at the injured site remained viable in the site of the lesion.INTRODUÇÃO: A lesão traumática da medula espinal consiste numa das mais incapacitantes lesões que o ser humano pode sofrer e tem despertado grande interesse no conhecimento das alterações histopatológicas, bioquímicas, funcionais e principalmente na busca de métodos de prevenção e tratamento. OBJETIVO: Propor um modelo experimental de transplante de células do sistema nervoso fetal de ratos para o sítio de lesão medular de ratos adultos que permitisse sua sobrevivência e integração para possibilitar protocolos de pesquisa para identificar outros fatores de regeneração e recuperação funcional pós trauma raquimedular. MATERIAL E MÉTODOS: Utilizaram-se 15 ratos adultos que foram submetidos a laminectomia e lesão de 5mm de hemimelula realizada com auxílio de microscópio óptico. Os ratos tiveram seu sítio de lesão medular transplantado com células do

  8. Human fetal brain-derived neural stem/progenitor cells grafted into the adult epileptic brain restrain seizures in rat models of temporal lobe epilepsy.

    Science.gov (United States)

    Lee, Haejin; Yun, Seokhwan; Kim, Il-Sun; Lee, Il-Shin; Shin, Jeong Eun; Park, Soo Chul; Kim, Won-Joo; Park, Kook In

    2014-01-01

    Cell transplantation has been suggested as an alternative therapy for temporal lobe epilepsy (TLE) because this can suppress spontaneous recurrent seizures in animal models. To evaluate the therapeutic potential of human neural stem/progenitor cells (huNSPCs) for treating TLE, we transplanted huNSPCs, derived from an aborted fetal telencephalon at 13 weeks of gestation and expanded in culture as neurospheres over a long time period, into the epileptic hippocampus of fully kindled and pilocarpine-treated adult rats exhibiting TLE. In vitro, huNSPCs not only produced all three central nervous system neural cell types, but also differentiated into ganglionic eminences-derived γ-aminobutyric acid (GABA)-ergic interneurons and released GABA in response to the depolarization induced by a high K+ medium. NSPC grafting reduced behavioral seizure duration, afterdischarge duration on electroencephalograms, and seizure stage in the kindling model, as well as the frequency and the duration of spontaneous recurrent motor seizures in pilocarpine-induced animals. However, NSPC grafting neither improved spatial learning or memory function in pilocarpine-treated animals. Following transplantation, grafted cells showed extensive migration around the injection site, robust engraftment, and long-term survival, along with differentiation into β-tubulin III+ neurons (∼34%), APC-CC1+ oligodendrocytes (∼28%), and GFAP+ astrocytes (∼8%). Furthermore, among donor-derived cells, ∼24% produced GABA. Additionally, to explain the effect of seizure suppression after NSPC grafting, we examined the anticonvulsant glial cell-derived neurotrophic factor (GDNF) levels in host hippocampal astrocytes and mossy fiber sprouting into the supragranular layer of the dentate gyrus in the epileptic brain. Grafted cells restored the expression of GDNF in host astrocytes but did not reverse the mossy fiber sprouting, eliminating the latter as potential mechanism. These results suggest that human fetal

  9. Induction of pancreatic duct cells of neonatal rats into insulin-producing cells with fetal bovine serum: A natural protocol and its use for patch clamp experiments

    Institute of Scientific and Technical Information of China (English)

    San-Hua Leng; Fu-Er Lu

    2005-01-01

    AIM: To induce the pancreatic duct cells into endocrine cells with a new natural protocol for electrophysiological study.METHODS: The pancreatic duct cells of neonatal rats were isolated, cultured and induced into endocrine oells with 15% fetal bovine serum for a period of 20 d. During this period, insulin secretion, MTT value, and morphological change of neonatal and adult pancreatic islet cells were comparatively investigated. Pancreatic β-cells were identified by morphological and electrophysiological characteristics, while ATP sensitive potassium channels(KATP), voltage-dependent potassium channels (KV), and voltage-dependent calcium channels (KCA) in β-cells were identified by patch clamp technique.RESULTS: After incubation with fetal bovine serum, the neonatal duct cells budded out, changed from duct-like cells into islet clusters. In the first 4 d, MTT value and insulin secretion increased slowly (MTT value from 0.024±0.003 to0.028±0.003, insulin secretion from 2.6±0.6to 3.1±0.8 mIU/L). Then MTT value and insulin secretion increased quickly from d 5 to d 10 (MTT value from 0.028±0.003 to 0.052±0.008, insulin secretion from 3.1±0.8to 18.3±2.6 mIU/L), then reached high plateau (MTT value >0.052±0.008, insulin secretion >18.3±2.6 mIU/L).In contrast, for the isolated adult pancreatic islet cells,both insulin release and MTT value were stable in the first 4 d (MTT value from 0.029±0.01 to 0.031±0.011,insulin secretion from 13.9±3.1 to 14.3±3.3 mIU/L), but afterwards they reduced gradually (MTT value <0.031±0.011, insulin secretion <8.2±1.5 mIU/L), and the pancrearic islet cells became dispersed, broken or atrophied correspondingly. The differentiated neonatal cells were identified as pancreatic islet cells by dithizone staining method, and pancreatic β-cells were further identified by both morphological features and electrophysiological characteristics, i.e. the existence of recording currents from KATP KV, and KCA.CONCLUSION: Islet

  10. Regulation of germ cell meiosis in the fetal ovary.

    Science.gov (United States)

    Spiller, Cassy M; Bowles, Josephine; Koopman, Peter

    2012-01-01

    Fertility depends on correct regulation of meiosis, the special form of cell division that gives rise to haploid gametes. In female mammals, germ cells enter meiosis during fetal ovarian development, while germ cells in males avoid entering meiosis until puberty. Decades of research have shown that meiotic entry, and germ cell sex determination, are not initiated intrinsically within the germ cells. Instead, meiosis is induced by signals produced by the surrounding somatic cells. More recently, retinoic acid (RA), the active derivative of vitamin A, has been implicated in meiotic induction during fetal XX and postnatal XY germ cell development. Evidence for an intricate system of RA synthesis and degradation in the fetal ovary and testis has emerged, explaining past observations of infertility in vitamin A-deficient rodents. Here we review how meiosis is triggered in fetal ovarian germ cells, paying special attention to the role of RA in this process.

  11. Cloning of the Eukaryotic Expression Vector with Nerve Growth Factor in Rats and Its Effects on Proliferation and Differentiation of Mesencephal Neural Stem Cells of Fetal Rats

    Institute of Scientific and Technical Information of China (English)

    Minhua LIN; Lin YANG; Rong FU; Hongyang ZHAO

    2008-01-01

    Summary: The eukaryotic expression vector containing full-length cDNA sequence of rate nerve growth factor (NGF) β subunit was constructed and its effects on proliferation and differentiation of neural stem cells were observed. By using PCR, full-length cDNA sequence of NGF β subunit in rats was cloned and ligated into the eukaryotic expression vector pEGFP-N1-NGE The recombinant plasmid pEGFP-N1-NGF was transfected into the mesencephal neural stem cells of embryonic rats by Lipofectamin and transiently expressed. MTT method was used to determine the effects of NGF on proliferation of neural stem cells, and under phase-contrast microscopy, the effects of NGF on growth of nervous processes following differentiation of neural stem cells were observed. Sequence analysis indicated that the cloned full-length cDNA sequence of rat NGF β was identical to that of published sequence encoding NGF in gene GeneBank. The transfection of recombinant plasmid pEGFP-N1-NGF into mesencephal neural stem cells of embryonic rats could obviously promote proliferation of neural stem cells and faciliate the growth of neural stem cells-derived nerve cells. It was suggested that neural stem cells could be used as a vehicle of gene transfer, and the expression of NGF β subunit in the neural stem cells could promote the growth of nerve cells derived from neural stem cells.

  12. Placental Protein 13 Administration to Pregnant Rats Lowers Blood Pressure and Augments Fetal Growth and Venous Remodeling.

    Science.gov (United States)

    Gizurarson, Sveinbjorn; Sigurdardottir, Elisabet Run; Meiri, Hamutal; Huppertz, Berthold; Sammar, Marei; Sharabi-Nov, Adi; Mandalá, Maurizio; Osol, George

    2016-01-01

    Reduced first-trimester concentrations of placental protein 13 (PP13) are associated with subsequent development of preeclampsia, a major pregnancy disorder. We previously showed that PP13 has a vasodilatory effect, reduces blood pressure and augments expansive remodeling of the uteroplacental vasculature in pregnant rats. In this study, slow-release osmotic pumps were implanted in gravid rats (on day 8) to provide 1 week of PP13 supplementation. Treatment was associated with a reversible blood pressure reduction that returned to normal on day 15. In addition, PP13 caused venous expansion that is larger in the venous branches closer to the placenta. Then, it increased placental and pup weights. Similar administration of a truncated PP13 variant (DelT221) that is unable to bind carbohydrates (a rare spontaneous mutation associated with a high frequency of severe early preeclampsia among Blacks in South Africa) produced a hypotensive effect similar to the full-length molecule, but without venous remodeling and increased placental and pup weights. These results indicate the importance of PP13 carbohydrate binding for inducing vascular remodeling and improving reproductive outcome. Future studies are needed to determine whether beneficial effects would be evident in animal models of preeclampsia or in women predisposed to the development of preeclampsia.

  13. 硝基还原酶结构域蛋白1在大鼠睾丸组织中特异性高表达在人类睾丸癌中表达下调%Testis Selective Expression of NOR1 Gene in Rat and Down Regulation of NOR1 Protein in Human Testicular Germ Cell Tumors

    Institute of Scientific and Technical Information of China (English)

    王卫; 李小玲; 李文娟; 易梅; 唐珂; 郑盼; 向波; 李桂源

    2013-01-01

    Rat oxidored nitro domain containing protein 1 (rNOR1) was identified and characterized.Isolated rNOR1 cDNA consisted of 1 418 base pairs that encoded a 379-amino acid protein,and the amino acid sequence was 89% and 93% identical to that of human NOR1 (hNOR1) and mouse NOR1 (mNOR1),respectively.The rat NOR1 protein contained a putative conserved domain belong to OSCP1 superfamily.The message for rNOR1 is highly detected in rat testis.Furthermore,human NOR1 homologue is enriched in testis.By immunostaining human NOR1 protein was detected in human testicular tumors of different subtypes on tissue microarray.NOR1 was strongly immunostained in non-cancerous testicular tissues and embryonal carcinomas,while seminomatous tumour cells and differentiated nonseminomatous derivatives (teratoma,yolk sac tumor) stained less intensely.These data suggested that rNOR1 might serve as a testis-selective gene,and that altered NOR1 expression in testicular cancer may help us to elucidate the functions of NOR1 protein in germ line cells carcinogenesis.%通过克隆分离鉴定得到大鼠硝基还原酶结构域蛋白1(rNOR1),发现rNOR1 cDNA含有1 418个碱基,编码含379个氨基酸残基的rNOR1蛋白.rNOR1与人类NOR1 (hNOR1)和小鼠NOR1 (mNOR1)的同源性分别为89%和93%,这三种同源蛋白都含有OSCP1家族的保守结构域.rNOR1基因在大鼠睾丸中选择性高表达,而且与之同源的人类hNOR1也选择性高表达于睾丸中.通过免疫组化检测人类不同睾丸癌中的hNOR1蛋白表达,发现hNOR1蛋白在非癌变睾丸组织和胚胎性癌组织中高表达,而在精原细胞癌和分化型非精原细胞癌(畸胎瘤,卵黄囊瘤)中低表达.这些数据表明,hNOR1可能是一种睾丸选择性表达基因,睾丸癌hNOR1表达的改变或许可以帮助我们阐明hNOR1蛋白在生殖细胞系肿瘤发生中的功能.

  14. Synchronous rhabdomyosarcoma of the testis and kidney: A case ...

    African Journals Online (AJOL)

    Babatunde M. Duduyemi

    2015-04-15

    Apr 15, 2015 ... involvement of the paratesticular tissue, testis and the kidney are ... coma of the left testis, paratesticular tissue and right kidney was made by histology and .... ated muscles.1,9 Histologically, the embryonal and alveolar.

  15. Activin receptor subunits in normal and dysfunctional adult human testis

    DEFF Research Database (Denmark)

    Dias, V; Meachem, S; Rajpert-De Meyts, E

    2008-01-01

    The cellular sites of activin action and its regulation in the normal and dysfunctional adult human testis are unknown.......The cellular sites of activin action and its regulation in the normal and dysfunctional adult human testis are unknown....

  16. Plasma concentrations and placental immunostaining of interleukin-10 and tumornecrosis factor-α as predictors of alterations in the embryo-fetal organism and the placental development of diabetic rats

    Directory of Open Access Journals (Sweden)

    Y.K. Sinzato

    2011-03-01

    Full Text Available Interleukin-10 (IL-10 appears to be the key cytokine for the maintenance of pregnancy and inhibits the secretion of inflammatory cytokines such as tumor necrosis factor-α (TNF-α. However, there are no studies evaluating the profile of these cytokines in diabetic rat models. Thus, our aim was to analyze IL-10 and TNF-α immunostaining in placental tissue and their respective concentrations in maternal plasma during pregnancy in diabetic rats in order to determine whether these cytokines can be used as predictors of alterations in the embryo-fetal organism and in placental development. These parameters were evaluated in non-diabetic (control; N = 15 and Wistar rats with streptozotocin (STZ-induced diabetes (N = 15. At term, the dams (100 days of life were killed under anesthesia and plasma and placental samples were collected for IL-10 and TNF-α determinations by ELISA and immunohistochemistry, respectively. The reproductive performance was analyzed. Plasma IL-10 concentrations were reduced in STZ rats compared to controls (7.6 ± 4.5 vs 20.9 ± 8.1 pg/mL. The placental scores of immunostaining intensity did not differ between groups (P > 0.05. Prevalence analysis showed that the IL-10 expression followed TNF-α expression, showing a balance between them. STZ rats also presented impaired reproductive performance and reduced plasma IL-10 levels related to damage during early embryonic development. However, the increased placental IL-10 as a compensatory mechanism for the deficit of maternal regulation permitted embryo development. Therefore, the data suggest that IL-10 can be used as a predictor of changes in the embryo-fetal organism and in placental development in pregnant diabetic rats.

  17. Effects of Post-coital Administration of Alkaloids from Senna alata (Linn. Roxb) Leaves on some Fetal and Maternal Outcomes of Pregnant Rats.

    Science.gov (United States)

    Yakubu, Musa Toyin; Musa, Isa Fakai

    2012-10-01

    The abortifacient claim of Senna alata (S. alata) was scientifically validated recently with alkaloids speculated to be the bioactive agent. This speculation is yet to be substantiated or refuted by scientific evidence. The present study was aimed to investigate the pregnancy terminating effects of the alkaloids from S. alata leaves. Twenty four Pregnant rats (143.99±1.21 g) allocated randomly to four groups: A, B, C and D respectively received, 0.5 ml of distilled water, 250, 500 and 1000 mg/kg body weight of the S. alata extracted alkaloids orally, once daily from day 10 until day 18 post-coitum. The indices of abortifacient were evaluated at the end of the exposure period. The results were analyzed by both the analysis of variance and Duncan's multiple range test and p < 0.05 was considered as statistically significant. Thin-layer chromatographic separation produced five spots with Rf values of 0.28, 0.33, 0.39, 0.47 and 0.55 which gave positive reaction with Meyer's and Wagner's reagents, respectively. The number of implantation sites and corpora lutea, as well as the concentrations of FSH, LH, progesterone, weight of uterus, uterine/ body weight ratio, glucose and cholesterol decreased significantly (p < 0.05) whereas the resorption index, pre- and post-implantation losses, uterine protein content and alkaline phosphatase activity increased significantly. None of the alkaloid treated animals presented with provoked vaginal opening or bleeding except fetal deaths. The alkaloid decreased the maternal weight gain, as well as feed and water intake. Overall, the alkaloids from S. alata leaves exhibited anti-implantation, anti-gonadotropic, anti-progesteronic, embryonic resorptive, feto-maternal toxic activities but not complete abortifacient. The alkaloids alone may not be the sole abortifacient bioactive agent in the leaf extract.

  18. Assessment of the Protective Role of Prenatal Zinc versus Insulin Supplementation on Fetal Cardiac Damage Induced by Maternal Diabetes in Rat Using Caspase-3 and KI67 Immunohistochemical Stains

    Directory of Open Access Journals (Sweden)

    Ahmed S. Shams

    2016-01-01

    Full Text Available Maternal diabetes mellitus (DM affects early organogenesis. Metabolic disorders of DM are associated with a depleted zinc status. This study evaluated the effect of maternal DM on cardiac development of rat fetuses and protective roles of prenatal zinc versus insulin supplementation. Pregnant rats were divided into 4 groups ((I control, (II STZ-induced DM, (III STZ-induced DM treated with Zn, and (IV STZ induced DM treated with insulin, all sacrificed on GD 20. Fetal heart weight of diabetic rats showed significant decrease compared to controls (P<0.05. H&E stained section of controls had normal appearance of the myocardium, compared to diabetics that showed myocardial disarray with characteristic degenerative changes. Sections of zinc treated group showed restored architecture of normal myofibrils with minimal degenerative changes, while those of insulin treated group show partial restoration of the normal architecture of cardiomyocytes with focal improvement of cardiac tissue. Caspase-3 immunostained slides showed positive cytoplasmic immunoreactivity in diabetic group. But KI67 immunostained slides revealed negative nuclear immunoreaction in diabetics. We observed that gestational diabetes was associated with increased risk of fetal myocardial damage that might be caused by increased apoptotic level. Treating diabetic pregnant subjects with zinc and insulin was associated with improvement in myocardial integrity.

  19. Cloning the promoter for transforming growth factor-beta type III receptor. Basal and conditional expression in fetal rat osteoblasts

    Science.gov (United States)

    Ji, C.; Chen, Y.; McCarthy, T. L.; Centrella, M.

    1999-01-01

    Transforming growth factor-beta binds to three high affinity cell surface molecules that directly or indirectly regulate its biological effects. The type III receptor (TRIII) is a proteoglycan that lacks significant intracellular signaling or enzymatic motifs but may facilitate transforming growth factor-beta binding to other receptors, stabilize multimeric receptor complexes, or segregate growth factor from activating receptors. Because various agents or events that regulate osteoblast function rapidly modulate TRIII expression, we cloned the 5' region of the rat TRIII gene to assess possible control elements. DNA fragments from this region directed high reporter gene expression in osteoblasts. Sequencing showed no consensus TATA or CCAAT boxes, whereas several nuclear factors binding sequences within the 3' region of the promoter co-mapped with multiple transcription initiation sites, DNase I footprints, gel mobility shift analysis, or loss of activity by deletion or mutation. An upstream enhancer was evident 5' proximal to nucleotide -979, and a silencer region occurred between nucleotides -2014 and -2194. Glucocorticoid sensitivity mapped between nucleotides -687 and -253, whereas bone morphogenetic protein 2 sensitivity co-mapped within the silencer region. Thus, the TRIII promoter contains cooperative basal elements and dispersed growth factor- and hormone-sensitive regulatory regions that can control TRIII expression by osteoblasts.

  20. Effects of engrafted neural stem cells derived from fetal rat on model rat with Parkinson's diseases%鼠胚神经干细胞移植对帕金森模型大鼠的治疗作用

    Institute of Scientific and Technical Information of China (English)

    蒋明; 陈新成; 吴旻; 邓引生; 陶轶

    2011-01-01

    背景:干细胞移植是治疗帕金森的有潜力的方法之一.目的:观察神经干细胞纹状体移植对帕金森模型大鼠旋转行为及脑内多巴胺含量的影响.方法:采用6-羟基多巴胺定点注射毁损黑质纹状体的方法构建帕金森大鼠模型;向造模成功的大鼠纹状体内分别移植1×106(共计20 μL)的第3代胚鼠神经干细胞或等量生理盐水.结果与结论:神经干细胞移植后,帕金森大鼠的旋转行为明显改善.干细胞移植后3周,免疫组化检测发现移植干细胞的帕金森大鼠脑黑质部位酪氨酸羟化酶阳性细胞数增多,纹状体内可见酪氨酸羟化酶阳性细胞;荧光显微镜下观察发现Hoechst 33324d标记神经干细胞在移植针道附近最为密集,并向远隔部位迁徙.干细胞移植后8周,高效液相色谱检测显示移植干细胞的帕金森大鼠纹状体内多巴胺含量明显增高(P < 0.01).说明神经干细胞脑内移植能够减轻6-羟基多巴胺引起的大鼠中脑黑质多巴胺能神经元的损伤,改善大鼠的旋转行为.%BACKGROUND: Stem cells transplantation is one of the potential methods for the treatment of Parkinson's diseases (PD). OBJECTIVE: To investigate the effect of neural stem cells engrafted into the striatum on rotational behavior and dopamine concentration of rat model with PD.METHODS: Rat models of PD were established by point injection with 6-hydroxy dopamine to damage nigrostriatal. The 1×106 (total 20 μL) passage 3 fetal rat neural stem cells or normal saline were injected into the striatum of the established rat model. RESULTS AND CONCLUSION: After neural stem cells were transplanted into the striatum. The rotational behavior of the PD rat was improved obviously. Three weeks later, the results of immun oh isto chemistry detection showed that the number of tyros in e hydroxylase-positive cells in the substantia nigra of transfected PD rat was increased obviously, and the tyrosine hydroxylase

  1. Expression, biosynthesis and release of preadipocyte factor-1/ delta-like protein/fetal antigen-1 in pancreatic -cells

    DEFF Research Database (Denmark)

    Friedrichsen, B N; Carlsson, C; Møldrup, A

    2003-01-01

    Preadipocyte factor-1 (Pref-1)/delta-like protein/fetal antigen-1 (FA1) is a member of the epidermal growth factor-like family. It is widely expressed in embryonic tissues, whereas in adults it is confined to the adrenal gland, the anterior pituitary, the endocrine pancreas, the testis and the ov......Preadipocyte factor-1 (Pref-1)/delta-like protein/fetal antigen-1 (FA1) is a member of the epidermal growth factor-like family. It is widely expressed in embryonic tissues, whereas in adults it is confined to the adrenal gland, the anterior pituitary, the endocrine pancreas, the testis...

  2. Carcinoma in situ in the testis

    DEFF Research Database (Denmark)

    Rørth, M; Rajpert-De Meyts, E; Andersson, L

    2000-01-01

    Carcinoma in situ (CIS) of the testis is a common precursor of germ-cell tumours in adults and adolescents, with the exception of spermatocytic seminoma. This article reviews existing knowledge on the pathobiology, genetic aspects and epidemiology of CIS, discusses current hypotheses concerning...

  3. Free radicals in adolescent varicocele testis.

    Science.gov (United States)

    Romeo, Carmelo; Santoro, Giuseppe

    2014-01-01

    We examine the relationship between the structure and function of the testis and the oxidative and nitrosative stress, determined by an excessive production of free radicals and/or decreased availability of antioxidant defenses, which occur in the testis of adolescents affected by varicocele. Moreover, the effects of surgical treatment on oxidative stress were provided. We conducted a PubMed and Medline search between 1980 and 2014 using "adolescent," "varicocele," "free radicals," "oxidative and nitrosative stress," "testis," and "seminiferous tubules" as keywords. Cross-references were checked in each of the studies, and relevant articles were retrieved. We conclude that increased concentration of free radicals, generated by conditions of hypoxia, hyperthermia, and hormonal dysfunction observed in adolescent affected by varicocele, can harm germ cells directly or indirectly by influencing nonspermatogenic cells and basal lamina. With regard to few available data in current literature, further clinical trials on the pre- and postoperative ROS and RNS levels together with morphological studies of the cellular component of the testis are fundamental for complete comprehension of the role played by free radicals in the pathogenesis of adolescent varicocele and could justify its pharmacological treatment with antioxidants.

  4. Alteration of marker enzymes in adenine-induced impaired testis and the interference of total flavonoids of herba epimedii in rats%腺嘌呤致大鼠睾丸损伤中标志酶的变化及淫羊藿总黄酮的干预作用

    Institute of Scientific and Technical Information of China (English)

    张作涛; 谢高宇; 陈凯; 齐敏友; 刘浩然

    2012-01-01

    目的 研究淫羊藿总黄酮(TFE)对腺嘌呤致大鼠睾丸损伤中标志酶的干预作用.方法 将70只Sprague Dawley雄性大鼠随机分为5组:正常对照组(蒸馏水灌胃)、模型组(蒸馏水灌胃)、TFE组(TFE 100 mg/kg灌胃)、维生素E组(维生素E 10 mg/kg灌胃)和甲基睾酮组(甲基睾酮5 mg/kg灌胃),每组14只.除正常对照组外,其余每组大鼠均予腺嘌呤150 mg/kg灌胃14 d建立大鼠睾丸病变模型,第15天开始各组大鼠分别给予相应处理.30 d后处死大鼠,称量睾丸、附睾、精囊腺及大鼠质量,计算脏器指数;检测血清睾酮、卵泡刺激素(FSH)、黄体生成素(LH);睾丸中乳酸脱氢酶(LDH)、酸性磷酸酶(ACP)、谷氨酰转肽酶(γ-GT)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力及丙二醛(MDA)含量.结果 与正常对照组比较,模型组各性腺脏器指数下降,血清睾酮下降,睾丸中LDH、ACP及γ-GT活力降低,MDA含量升高,差异有统计学意义(P<0.05).与模型组比较,TFE组大鼠脏器指数、血清睾酮水平及特异性酶类活力提高(P<0.05).结论 TFE可能通过促进睾酮释放及抗氧化作用而显著提高腺嘌呤致大鼠睾丸损伤中标志酶活力.%Objective To study the interference effect of total flavonoids of herba epimedii(TFE) on marker enzymes in adenine-induced impaired testis in rats. Methods 70 Sprague Dawley male rats were randomly divided into 5 groups of 14 rats each; normal control group(intravenous infusion of distilled water) ,model groupCgastric perfusion of distilled water) ,TFE groupCgastric perfu-sion of TFE 100 mg/kg) , Vitamin E groupCgastric perfusion of vitamin E 10 mg/kg) and methyl testosterone group (gastric perfusion of methyl-testosterone 5 mg/kg) ,Except rats in normal group,those in the rest groups were subjected to gastric perfusion of adenine 150 mg/kg for 14 days to establish the rat models of testicular lesion. Rats in each group were accepted corresponding

  5. Fetal syringomyelia.

    Science.gov (United States)

    Guo, Anne; Chitayat, David; Blaser, Susan; Keating, Sarah; Shannon, Patrick

    2014-08-06

    We explored the prevalence of syringomyelia in a series of 113 cases of fetal dysraphism and hindbrain crowding, of gestational age ranging from 17.5 to 34 weeks with the vast majority less than 26 weeks gestational age. We found syringomyelia in 13 cases of Chiari II malformations, 5 cases of Omphalocele/Exostrophy/Imperforate anus/Spinal abnormality (OEIS), 2 cases of Meckel Gruber syndrome and in a single pair of pyopagus conjoined twins. Secondary injury was not uncommon, with vernicomyelia in Chiari malformations, infarct like histology, or old hemorrhage in 8 cases of syringomyelia. Vernicomyelia did not occur in the absence of syrinx formation. The syringes extended from the sites of dysraphism, in ascending or descending patterns. The syringes were usually in a major proportion anatomically distinct from a dilated or denuded central canal and tended to be dorsal and paramedian or median. We suggest that fetal syringomyelia in Chiari II malformation and other dysraphic states is often established prior to midgestation, has contributions from the primary malformation as well as from secondary in utero injury and is anatomically and pathophysiologically distinct from post natal syringomyelia secondary to hindbrain crowding.

  6. Effective analysis on treatment of rat acute liver failure by human fetal hepatocyte transplantation%人胚胎肝细胞移植治疗大鼠急性肝衰竭的效果分析

    Institute of Scientific and Technical Information of China (English)

    刘凯歌; 尚红利; 赵慧; 牛春燕; 汪雯

    2011-01-01

    目的 探讨人胚胎肝细胞移植治疗急性肝衰竭(ALF)的疗效及能否成为移植细胞源.方法 采用四甲基偶氮唑盐法检测人胚胎肝细胞增殖情况;免疫细胞化学检测其ALB、细胞角蛋白-18(CK-18)的表达; D-氨基半乳糖(D-gal)药物诱导ALF的实验动物模型;人胚胎肝细胞移植治疗ALF的动物模型,包括移植组与对照组在肝功能指标[ALT、AST、碱性磷酸酶(ALP)、总胆红素(TBIL)]的差异性比较.免疫组织化学法检测植入脾脏中的人胚胎肝细胞ALB及CK-18的表达.结果 培养第5天左右细胞数量达到最高峰,每天完成4~5次分裂,胚胎肝细胞的生长曲线呈抛物线型.免疫细胞化学检测提示其具有表达ALB、CK-18的功能; D-gal 1.6 g/kg腹腔注射72 h后大鼠ALF模型制备成功;移植第3~5天后,移植组与对照组比较,肝功能(ALT、AST、ALP、TBIL)指标差异有统计学意义(P<0.01).植入脾内的肝细胞具有分泌并表达CK-18、ALB的功能.结论 人胚胎肝细胞脾内移植能有效治疗ALF,并可能成为肝细胞移植的靶细胞源.%Objective To investigate the effect of treating rat acute liver failure and alternative sources of cells for transplantation by human fetal hepatocyte transplantation Methods The proliferation,expression of albumin and cytokeratin-18 of human fetal hepatocyte were detected by MTT and immunocytochemistry.The animal models of rat acute liver failure were made by D-galactosamine.Hepatic functions.such as alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and total bilirubin were measured between the treated and the control groups.The expression of albumin and cytokeratin-18 of human fetal hepatocyte transplanted in spleen were detected by immunohistochemistry.Results The cell population reached a peak, when human fetal hepatocyte were cultivated for 5 d.The cell division had 4 - 5 times per day,its growth curve present parabola.Immunocytochemistry revealed the

  7. Expression of 5α-Reductase Type 2 Gene in Human Testis, Epididymis and Vas Deferens

    Institute of Scientific and Technical Information of China (English)

    刘德瑜; 吴燕婉; 罗宏志; 张桂元

    2002-01-01

    Objectives To study the expression pattern of 5α-reductase type 2 gene in human malereproductive organsMethods The expression level of 5α-reductase type 2 gene inhuman testis, epididymisand vas deferens tissues was determined by in situ hybridization using Digoxin labeled5α-reductase type 2 cRNA probe.Results The brown granules of hybridizing signals distributed in the cytoplasm ofSertoli and Leydig cells of the testis, the principle cells of epididymis and the epithe-lial cells of vas deferens, but there was no pos