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Sample records for adult ovarian granulosa

  1. Ovarian juvenile granulosa cell tumor associated with Maffucci's syndrome:case report

    Institute of Scientific and Technical Information of China (English)

    袁键群; 林小娜; 许敬尧; 祝佳; 郑伟良

    2004-01-01

    @@ Granulosa cell tumors (GCTs) are the most common ovarian sex-cord stromal tumors. Two histopathologically well defined patterns of GCTs are known: adult granulosa cell tumor (AGCT) and juvenile granulosa cell tumor (JGCT). JGCTs are rare and those associated with enchondromatosis are much rarer. A review of the literature revealed four previous cases of JGCT were associated with Maffucci ' s syndrome (MS),1-4 and nine with Ollier ' s disease (OD). This report describes ovarian JGCT with MS in a 21-year-old woman, and reviews the clinicopathological causes of both disorders.

  2. Adult granulosa cell tumor of the testis masquerading as hydrocele

    Directory of Open Access Journals (Sweden)

    Archana George Vallonthaiel

    2015-12-01

    Full Text Available Adult testicular granulosa cell tumor is a rare, potentially malignant sex cord-stromal tumor, of which 30 cases have been described to date. We report the case of a 43-year-old male who complained of a left testicular swelling. Scrotal ultrasound showed a cystic lesion, suggestive of hydrocele. However, due to a clinical suspicion of a solid-cystic neoplasm, a high inguinal orchidectomy was performed, which, on pathological examination, was diagnosed as adult granulosa cell tumor. Adult testicular granulosa cell tumors have aggressive behaviour as compared to their ovarian counterparts. They may rarely be predominantly cystic and present as hydrocele. Lymph node and distant metastases have been reported in few cases. Role of MIB-1 labelling index in prognostication is not well defined. Therefore, their recognition and documentation of their behaviour is important from a diagnostic, prognostic and therapeutic point of view.

  3. File list: Oth.Utr.50.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  4. File list: Unc.Utr.20.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. File list: Unc.Utr.50.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  6. File list: Pol.Utr.20.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  7. File list: Pol.Utr.10.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  8. File list: Unc.Utr.05.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Utr.05.AllAg.Ovarian_granulosa_cells hg19 Unclassified Uterus Ovarian granulosa... cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Unc.Utr.05.AllAg.Ovarian_granulosa_cells.bed ...

  9. File list: His.Utr.20.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  10. File list: ALL.Utr.50.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  11. File list: ALL.Utr.10.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  12. File list: ALL.Utr.20.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  13. File list: DNS.Utr.10.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Utr.10.AllAg.Ovarian_granulosa_cells hg19 DNase-seq Uterus Ovarian granulosa ce...lls http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Utr.10.AllAg.Ovarian_granulosa_cells.bed ...

  14. File list: His.Utr.50.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  15. File list: Pol.Utr.05.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  16. File list: DNS.Utr.05.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  17. File list: ALL.Utr.05.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Utr.05.AllAg.Ovarian_granulosa_cells hg19 All antigens Uterus Ovarian granulosa... cells SRX610672,SRX610673,SRX610674 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/ALL.Utr.05.AllAg.Ovarian_granulosa_cells.bed ...

  18. File list: DNS.Utr.20.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Utr.20.AllAg.Ovarian_granulosa_cells hg19 DNase-seq Uterus Ovarian granulosa ce...lls http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Utr.20.AllAg.Ovarian_granulosa_cells.bed ...

  19. File list: Oth.Utr.20.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Utr.20.AllAg.Ovarian_granulosa_cells hg19 TFs and others Uterus Ovarian granulo...sa cells SRX610674,SRX610673,SRX610672 http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Oth.Utr.20.AllAg.Ovarian_granulosa_cells.bed ...

  20. File list: His.Utr.05.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: Pol.Utr.50.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Utr.50.AllAg.Ovarian_granulosa_cells hg19 RNA polymerase Uterus Ovarian granulo...sa cells http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/Pol.Utr.50.AllAg.Ovarian_granulosa_cells.bed ...

  2. File list: His.Utr.10.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Utr.10.AllAg.Ovarian_granulosa_cells hg19 Histone Uterus Ovarian granulosa cell...s http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/His.Utr.10.AllAg.Ovarian_granulosa_cells.bed ...

  3. File list: DNS.Utr.50.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Utr.50.AllAg.Ovarian_granulosa_cells hg19 DNase-seq Uterus Ovarian granulosa ce...lls http://dbarchive.biosciencedbc.jp/kyushu-u/hg19/assembled/DNS.Utr.50.AllAg.Ovarian_granulosa_cells.bed ...

  4. File list: Oth.Utr.10.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  5. Flow cytometric DNA ploidy analysis of ovarian granulosa cell tumors

    NARCIS (Netherlands)

    D. Chadha; C.J. Cornelisse; A. Schabert (A.)

    1990-01-01

    textabstractAbstract The nuclear DNA content of 50 ovarian tumors initially diagnosed as granulosa cell tumors was measured by flow cytometry using paraffin-embedded archival material. The follow-up period of the patients ranged from 4 months to 19 years. Thirty-eight tumors were diploid or near-dip

  6. Extracellular matrix of the bovine ovarian membrana granulosa.

    Science.gov (United States)

    Rodgers, R J; Irving Rodgers, H F

    2002-05-31

    Much is known about the control of the development of ovarian follicles by growth factors and hormones. The study of extracellular matrix in the ovary, though, is a relatively new area. To date much research has focused on identifying the matrix components present, and more recently, its production and the physiological roles. In this review we focus on the changes that occur in the follicular basal lamina from primordial follicles through to ovulation and formation of the corpus luteum, the changes that occur during follicular atresia, and we discuss our observations of a novel matrix which forms in the membrana granulosa. The follicular basal lamina changes considerably during follicular development in its expression pattern of type IV collagens. Of the laminin chains examined, there appears only to be an increase in amount, except for laminin alpha2. It is expressed only in a small proportion of healthy antral follicles and in the majority of atretic antral follicles. Call-Exner bodies have the same composition as the basal lamina, except they do not contain laminin alpha2, even when the follicular basal lamina does. The novel matrix that develops within the membrana granulosa is similar in composition to Call-Exner bodies which occur predominantly in preantral follicles, except that it is far more common in large antral follicles, does not induce polarization of the surrounding granulosa cells, and does not contain follicular fluid-like material as the Call-Exner bodies of some species do. The expression of this matrix occurs prior to and during the time when granulosa cells express steroidogenic enzymes. It does not exist in corpora lutea. In addition large luteal cells, derived from granulosa cells, do not appear to have a basal lamina. These findings suggest that the maturational changes in the membrana granulosa are accompanied by changes in the matrix. PMID:12044919

  7. [Hormonal therapy of advanced or relapsed ovarian granulosa cell tumor].

    Science.gov (United States)

    Sun, H; Bai, P

    2016-07-01

    Ovarian granulosa cell tumor is a rare gynecologic malignancy with hormonal activity. Surgical excision is the standard treatment for this disease. Most patients present excellent short term prognosis, however, late relapse often occurs, even after many years. Viable treatments of advanced or relapsed granulosa cell tumor are still limited, and the optimal therapy method has not been established. Compared with chemotherapy and radiotherapy, hormonal therapy is a well-tolerated treatment which can be administrated over a long period of time without serious side effects, and the combined application of hormones may achieve a better outcome. Therefore, hormonal therapy has been suggested as a potential treatment option for patients with advanced or relapsed granulosa cell tumor, and to extend the tumor-free interval and attenuate the disease progression. Future researches should be focused on the identification of the hormonal therapy which may provide the greatest clinical benefit, comparing and analyzing the effects of different combined therapeutic regimens of hormone drugs, and on the synthesis of drugs highly activating estrogen receptor β expressed in the granulosa cell tumor cells. PMID:27531259

  8. File list: NoD.Utr.50.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  9. File list: InP.Utr.20.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  10. File list: NoD.Utr.05.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  11. File list: NoD.Utr.10.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  12. File list: InP.Utr.10.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  13. File list: InP.Utr.05.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  14. File list: NoD.Utr.20.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  15. File list: InP.Utr.50.AllAg.Ovarian_granulosa_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  16. A rare case of ovarian granulosa cell tumour in an adolescent girl with secondary amenorrhea and virilisation

    Directory of Open Access Journals (Sweden)

    Arun Nayak

    2015-10-01

    Full Text Available Sex cord stromal ovarian tumors account for about 5-8% of all ovarian malignancies. Granulosa cell tumor is an estrogen secreting low grade malignant tumor and is seen in women of all ages with 2% bilaterality. Based upon histology, these neoplasms can be classified as adult and juvenile Granulosa cell tumors. Pre-pubertal lesions present clinically with sexual pseudo precocity whereas post-pubertal lesions present with menstrual irregularities or secondary amenorrhea or postmenopausal bleeding. This case report presents a rare case of Granulosa cell tumor with clinical presentation mimicking virilizing ovarian neoplasm in a 19 year old girl with history of abdominal swelling, secondary amenorrhea and virilization since one year duration. Clinical examination revealed a 20-22 weeks size abdominal mass, cystic in consistency, arising from pelvis and CT scan suggested presence of mucinous cystadenoma with solid areas with suspected malignancy. Exploratory laparotomy with right salpingo-oophorectomy was performed with staging as tumor was found confined to ovary with no involvement of other ovary or any other pelvic organ or peritoneum. Therefore, disease was staged as stage 1A. Histopathological examination confirmed the presence of Granulosa cell tumor with fibrothecomatous areas. [Int J Reprod Contracept Obstet Gynecol 2015; 4(5.000: 1653-1656

  17. Dynamics of the membrana granulosa during expansion of the ovarian follicular antrum.

    Science.gov (United States)

    Rodgers, R J; Irving-Rodgers, H F; van Wezel, I L; Krupa, M; Lavranos, T C

    2001-01-22

    As an endocrine organ, the ovary has some unique characteristics. The formation, the maturation and the regression of the hormone producing cells really determine the timing, the amount and the type of hormone secreted. Here, we focus on the granulosa cells of ovarian follicles which express 17beta-hydroxysteroid dehydrogenase type 1 and cytochrome P450 aromatase. Follicles only produce estradiol late in follicular development before either ovulation or atresia ensues. We discuss the evidence that the membrana granulosa has many characteristics in common with other epithelia, including that it arises from stem cells. The corollary of this is that individual cells within the membrana granulosa are of different ages or stages of specialization. This is evident as regional differences across the membrana granulosa in terms of cell ages, shapes, gene expression, and even behaviour on cell death. We discuss theoretical considerations of the effects of antrum formation on the behavior of the membrana granulosa, and show evidence for differences between follicles in cell shapes, basal lamina phenotypes and location of younger cells, which we speculate is due to different rates of antrum expansion. Clearly, the membrana granulosa is dynamic, and this could explain much about the differences in the behaviors of cells from within the membrana granulosa, and between ovarian follicles. PMID:11165009

  18. Apoptosis and Expression of Protein TRAIL in Granulosa Cells of Rats with Polycystic Ovarian Syndrome

    Institute of Scientific and Technical Information of China (English)

    ZHANG Juan; ZHU Guijin; WANG Xinrong; XU Bei; HU Linli

    2007-01-01

    The relationship between apoptosis of granulosa cells and follicle development arrest in polycystic ovarian syndrome (PCOS) rats, and the contribution of tumor necrosis factor related apoptosis inducing ligand (TRAIL) in apoptosis of granulosa cells were explored. By using sodium prasterone sulfate rat PCOS model was induced. The apoptosis of granulosa cells in ovaries of rats was observed by TdT-mediated dUTP-biotin nick end-labeling (TUNEL), and the expression of TRAIL protein and mRNA in granulosa cells was detected by using immunhistochemical staining and reverse transcription polymerase chain reaction (RT-PCR) respectively. The apoptotic rate and the expression of protein TRAIL in granulosa cells were significantly higher in antral follicles from the PCOS rats than in those from the control rats (P<0.01, P<0.05). There was no significant difference in apoptotic rate and the expression of TRAIL protein in granulosa cells of preantral follicles between the PCOS rats and the control rats (P>0.05). No apoptosis and the expression of TRAIL protein in granulosa cells of primordial follicles were found in the two groups. The expression of TRAIL mRNA was significantly stronger in granulosa cells from the PCOS rats than in those from the control rats (P<0.01). It was suggested that the apoptotic rate in granulosa cells was significantly higher in antral follicle from the PCOS rats than in those from the control rats. TRAIL played a role in regulating the apoptosis of granulosa cells in PCOS rats.

  19. Defective CFTR-regulated granulosa cell proliferation in polycystic ovarian syndrome.

    Science.gov (United States)

    Chen, Hui; Guo, Jing Hui; Zhang, Xiao Hu; Chan, Hsiao Chang

    2015-05-01

    Polycystic ovarian syndrome (PCOS) is one of the most frequent causes of female infertility, featured by abnormal hormone profile, chronic oligo/anovulation, and presence of multiple cystic follicles in the ovary. However, the mechanism underlying the abnormal folliculogenesis remains obscure. We have previously demonstrated that CFTR, a cAMP-dependent Cl(-) and HCO3 (-) conducting anion channel, is expressed in the granulosa cells and its expression is downregulated in PCOS rat models and human patients. In this study, we aimed to investigate the possible involvement of downregulation of CFTR in the impaired follicle development in PCOS using two rat PCOS models and primary culture of granulosa cells. Our results indicated that the downregulation of CFTR in the cystic follicles was accompanied by reduced expression of proliferating cell nuclear antigen (PCNA), in rat PCOS models. In addition, knockdown or inhibition of CFTR in granulosa cell culture resulted in reduced cell viability and downregulation of PCNA. We further demonstrated that CFTR regulated both basal and FSH-stimulated granulosa cell proliferation through the HCO3 (-)/sAC/PKA pathway leading to ERK phosphorylation and its downstream target cyclin D2 (Ccnd2) upregulation. Reduced ERK phosphorylation and CCND2 were found in ovaries of rat PCOS model compared with the control. This study suggests that CFTR is required for normal follicle development and that its downregulation in PCOS may inhibit granulosa cell proliferation, resulting in abnormal follicle development in PCOS.

  20. Markers of stem cells in human ovarian granulosa cells: is there a clinical significance in ART?

    Directory of Open Access Journals (Sweden)

    Varras Michail

    2012-11-01

    Full Text Available Abstract Background The purpose of the study was to determine the incidence of gene expression of Oct-4 and DAZL, which are typical markers for stem cells, in human granulosa cells during ovarian stimulation in women with normal FSH levels undergoing IVF or ICSI and to discover any clinical significance of such expression in ART. Methods Twenty one women underwent ovulation induction for IVF or ICSI and ET with standard GnRH analogue-recombinant FSH protocol. Infertility causes were male and tubal factor. Cumulus–mature oocyte complexes were denuded separately and granulosa cells were analyzed for each patient separately using quantitative reverse-transcription–polymerase chain reaction analysis for Oct-4 and DAZL gene expression with G6PD gene as internal standard. Results G6PD and Oct-4 mRNA was detected in the granulosa cells in 47.6% (10/21. The median of Oct-4 mRNA/G6PD mRNA was 1.75 with intra-quarteral range from 0.10 to 98.21. The OCT-4 mRNA expression was statistically significantly correlated with the number of oocytes retrieved; when the Oct-4 mRNA expression was higher, then more than six oocytes were retrieved (p=0.037, Wilcoxon rank-sum. No detection of DAZL mRNA was found in granulosa cells. There was no additional statistically significant correlation between the levels of Oct-4 expression and FSH basal levels or estradiol peak levels or dosage of FSH for ovulation induction. No association was found between the presence or absence of Oct-4 mRNA expression in granulosa cells and ovarian response to gonadotropin stimulation. Also, no influence on pregnancy was observed between the presence or absence of Oct-4 mRNA expression in granulosa cells or to its expression levels accordingly. Conclusions Expression of OCT-4 mRNA, which is a typical stem cell marker and absence of expression of DAZL mRNA, which is a typical germ cell marker, suggest that a subpopulation of luteinized granulosa cells in healthy ovarian follicles (47

  1. Effect of the methoxychlor metabolite HPTE on the rat ovarian granulosa cell transcriptome in vitro.

    Science.gov (United States)

    Harvey, Craig N; Esmail, Mahmoud; Wang, Qi; Brooks, Andrew I; Zachow, Rob; Uzumcu, Mehmet

    2009-07-01

    Ovarian granulosa cells play a central role in steroidogenesis, which is critical for female reproduction. Follicle-stimulating hormone (FSH) promotes cyclic adenosine monophosphate (cAMP)-mediated signaling to regulate granulosa cell steroidogenesis. We have shown previously that 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE) inhibits FSH- and dibutyryl cAMP-stimulated steroidogenesis and affects the messenger RNA levels of steroidogenic pathway enzymes in rat granulosa cells. However, HPTE showed a differential effect in FSH- and cAMP-stimulated cells in that HPTE more completely blocked FSH- when compared to cAMP-driven steroidogenesis. The objective of this study was to analyze the effects of HPTE on global gene expression profiles in untreated granulosa cells and those challenged with FSH or cAMP. Granulosa cells from immature rats were cultured with 0, 1, 5, or 10 microM HPTE in the presence or absence of either 3 ng FSH/ml or 1mM cAMP for 48 h. Total RNA was isolated for real-time quantitative PCR and microarray analysis using the GeneChip Rat Genome 230 2.0 and ArrayAssist Microarray Suite. An investigation of changes in gene expression across all HPTE treatments showed that HPTE altered more genes in FSH- (approximately 670 genes) than in cAMP-stimulated cells (approximately 366 genes). Analysis confirmed that HPTE more effectively inhibited FSH- than cAMP-induced steroid pathway gene expression and steroidogenesis. Furthermore, expression patterns of novel genes regulating signal transduction, transport, cell cycle, adhesion, differentiation, motility and growth, apoptosis, development, and metabolism were all altered by HPTE. This study further established that HPTE exerts differential effects within the granulosa cell steroidogenic pathway and revealed that these effects include broader changes in gene expression.

  2. DOSE-RESPONSE OF PORCINE OVARIAN GRANULOSA CELLS TO AMYGDALIN TREATMENT COMBINED WITH DEOXYNIVALENOL

    Directory of Open Access Journals (Sweden)

    Marek Halenár

    2014-02-01

    Full Text Available Amygdalin is one of many nitrilosides, which are natural cyanide-containing substances abundant in the seeds of apricots, almond, peaches, apples, and other rosaceous plants. It is a controversial anti-tumor natural product that has been used as an alternative cancer drug for many years. On the other hand, one of the most widely distributed mycotoxin contaminating food and animal feed is deoxynivalenol (DON. Deoxynivalenol has adverse effects on humans, animals, and crops that result in illnesses. The aim of the in vitro study was to investigated the effect of natural substance amygdalin at the selected doses (1, 10, 100, 1000, 10 000 µg/mL in combination with deoxynivalenol (1000 ng/mL on secretion of steroid hormones (progesterone and estradiol by ovarian granulosa cells (GCs from cyclic pigs. Our results showed that the releasing of progesterone and estradiol by ovarian granulosa cells was affected by amygdalin plus DON addition. The secretion of progesterone by ovarian GCs was significantly (P≤0.05 affected by administration of both compounds in all experimental groups. Similarly, estradiol releasing by GCs was significantly (P≤0.05 increased in experimental groups with amygdalin (10, 100 and 10 000 µg/mL plus DON (1000 ng/mL addition. Amygdalin treatment combined with DON caused increase of steroid hormones release by ovarian granulosa cells. Our findings suggest possible involvement of these natural substances (amygdalin and deoxynivalenol in the regulation process of steroidogenesis. In conclusion, results from this experiment contribute to knowledge about interaction between two different natural compounds and their positive or negative interferences with ovarian functions.

  3. Effects of leptin and neuropeptide Y on function of human ovarian granulosa cells in vitro

    Institute of Scientific and Technical Information of China (English)

    Song Qing; Chen Xiao-yan; Cao Zuan-sun; Mao Wen-jun

    2006-01-01

    Objective: To investigate the effects of leptin and neuropeptide Y on steroidogenesis of human ovarian granulosa cells in vitro. Methods: Human ovarian granulosa cells were isolated from follicular fluid obtained during oocyte retrieval of in vitro fertilization-embryo transfer program and cultured for 2 days with various concentration of leptin(1,10,100 ng/ml) or neuropeptide Y (1×10-6, 1×10-7, 1×10-8 mol/L) alone or both,or with the combination of human chorionic gonadotropin (hCG 0, 20 IU/L). The medium was collected for estradiol (E2) and progesterone (P) measurements. Results: (1)Whether hCG existed or not, the adding of leptin did not alter estradiol and progesterone production by human granulosa cells (P>0.05).(2) Only when the concentration of neuropeptide Y was at 1×10-7mol/L,estradiol level was lower than that in the control (P<0.05).(3) The levels of estradiol in neuropeptide Y (1×10-7mol/L) plus hCG group were significantly higher than those with neuropeptide Y alone(P<0.05). (4) In the absence of hCG, the levels of estradiol in neuropeptide Y (1×10-7mol/L)plus leptin (10 ng/ml) group were significantly higher than those with neuropeptide Y(1×10-7mol/L)alone(P<0.05).Conclusions: (1)Leptin alone produced no direct effect on secretion of E2 and P from granulosa cells in vitro.(2)Neuropeptide Y alone may inhibit the secretion of E2, but the inhibition would probably be blocked with the presentation of hCG.(3)Leptin probably blocked the inhibition of neuropeptide Y on E2 secretion, and this may indicate that there were some coordination between leptin and neuropeptid Y on the level of ovarian function.

  4. ANTIOXIDANT STATUS AND EXPRESSION OF HEAT SHOCK PROTEIN OF COBALT-TREATED PORCINE OVARIAN GRANULOSA CELLS

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    Marcela Capcarová

    2013-02-01

    Full Text Available The aim of this study was to determine the activity of superoxide dismutase (SOD, total antioxidant status (TAS and expression of heat shock protein 70 (Hsp70 of porcine ovarian granulosa cells cultured in vitro after cobalt (Co administrations. Ovarian granulosa cells were incubated with cobalt sulphate administrations as follows: group E1 (0.09 mg.ml-1, group E2 (0.13 mg.ml-1, group E3 (0.17 mg.ml-1, group E4 (0.33 mg.ml-1, group E5 (0.5 mg.ml-1 and the control group without any additions for 18 h. Co administration developed stress reaction and promoted accumulation of Hsp70 what resulted in increasing activity of SOD. TAS of granulosa cells increased with higher doses of Co whereas low doses had no effect on this parameter. Trace elements can adversely affect animal female reproductive system and its functions, through either direct or indirect effects on oxidative stress induction.

  5. miR-22 inhibits mouse ovarian granulosa cell apoptosis by targeting SIRT1

    Science.gov (United States)

    Xiong, Fang; Hu, Lingqing; Zhang, Yun; Xiao, Xiao; Xiao, Juxia

    2016-01-01

    ABSTRACT Granulosa cell (GC) apoptosis has been shown to be involved in follicular atresia, which is a degenerative process in ovarian follicles of mammals. However, the mechanism underlying the regulation of follicular atresia, particularly by microRNAs, is not well known. Real-time PCR (RT-PCR) was used to detect the expression level of miR-22 in healthy follicles (HF), early atretic follicles (EAF), and progressively atretic follicles (PAF). Flow cytometry was performed to assess the apoptosis of mouse granulosa cells (mGCs) treated with miR-22 mimics or negative control (NC) mimics. Regulation of the expression of SIRT1 by miR-22 was evaluated using a luciferase reporter assay system. To investigate the roles of SIRT1 in mGC apoptosis, the endogenous SIRT1 gene in mGCs was knocked down using an siRNA specific for SIRT1. miR-22 was increased during follicular atresia and suppressed granulosa cell apoptosis. The results of the luciferase reporter assay indicated that SIRT1 was a target gene of miR-22. In addition, knockdown of SIRT1 attenuated apoptosis in mGCs. miR-22 inhibits mGC apoptosis by downregulating SIRT1 directly in vitro. This study provides important insights into understanding the regulation mechanism of ovarian follicle atresia. PMID:26912776

  6. Evidence for Existence of Immunoglobulins that Block Ovarian Granulosa Cell Growth in Vitro. A Putative Role in Resistant Ovary Syndrome?

    NARCIS (Netherlands)

    WEISSENBRUCH, MIRJAM M. van; HOEK, ANNEMIEKE; VLIET-BLEEKER, INGRID van; SCHOEMAKER, JOOP; DREXHAGE, HEMMO

    1991-01-01

    The sera of 26 patients with premature ovarian failure were examined in order to detect immunoglobulin-G (IgGs) that can block FSH-induced in vitro granulosa cell DNA synthesis via, a Feulgen cytochemical bioassay system. The IgGs of four patients with polycystic ovary-like disease, five postmenopau

  7. The effect of yucca on proliferation, apoptosis, and steroidogenesis of porcine ovarian granulosa cells

    Directory of Open Access Journals (Sweden)

    Aneta Štochmaľová

    2014-02-01

    Full Text Available Yucca shidigera is a medicinal plant native to Mexico. Is a plant widely used in folk medicine to treat a variety of ailmentary disorders, but its action on reproductive processes and possible mechanisms of such action remains unknown. Yucca schidigera extract contains a number of steroidal saponins that, because of their biological activity, have attracted attention from the food industry for many years. Yucca extract is used as a natural feed additive with positive effect to microflora, digestion, metabolism and to improve animal muscle growth. Its extract has been used as a foodstuff and folk medicine to treat a wide variety of diseases for many years. Nevertheless, it remaines unknown, whether consumption of yucca can affect reproductive system. The aim of this study was to examine the effects of yucca on basic ovarian cell functions - proliferation, apoptosis and steroidogenesis. Porcine ovarian granulosa cells were cultured with and without yucca extract (added at doses 0; 1; 10 and 100 μg.mL-1 of medium. Markers of proliferation (% of PCNA-positive cells and apoptosis (% cells containing bax were analysed by immunocytochemistry. Release of steroid hormones (progesterone and testosterone was measured by EIA. It was observed, that addition of yucca inhibited proliferation (expression of PCNA, increased apoptosis (expression of bax, stimulated progesterone and inhibited testosterone release. The ability of yucca to reduce ovarian cell proliferation, to promote ovarian cell apoptosis and affect steroidogenesis demonstrates the direct influence of yucca on female gonads. Furthermore, our observations suggest the multiple sites of action (proliferation, apoptosis, steroidogenesis of yucca on porcine ovarian cell functions. It is not to be excluded, that consumption of yucca can suppress female reproductive functions.

  8. Molecular cloning, expression analysis, and function of decorin in goat ovarian granulosa cells.

    Science.gov (United States)

    Peng, J Y; Gao, K X; Xin, H Y; Han, P; Zhu, G Q; Cao, B Y

    2016-10-01

    Decorin (DCN), a component of the extracellular matrix (ECM), participates in ECM assembly and influences cell proliferation and apoptosis in many mammalian tissues and cells. However, expression and function of DCN in the ovary remain unclear. This study cloned the full-length cDNA of goat DCN obtained from the ovary of an adult goat. Sequence analysis revealed that the putative DCN protein shared a highly conserved amino acid sequence with known mammalian homologs. The tissue distribution of DCN mRNA expression was evaluated by real-time PCR, and the results showed that DCN was widely expressed in the tissues of adult goat. Immunohistochemistry results suggested that DCN protein existed in the granulosa cells and oocytes from all types of follicles and theca cells of antral follicles. Moreover, hCG-induced DCN mRNA expression was significantly reduced by the inhibitors of protein kinase A, PI3K, or p38 kinase (P 0.05). These findings suggested that DCN regulates the apoptosis and cell cycle of granulosa cells. PMID:27565237

  9. Effects of ghrelin and its analogues on chicken ovarian granulosa cells.

    Science.gov (United States)

    Sirotkin, A V; Grossmann, R

    2008-02-01

    The aim of these in vitro experiments was (1) to examine the effects of ghrelin on the basic functions of ovarian cells (proliferation, apoptosis, secretory activity); (2) to determine the possible involvement of the GHS-R1a receptor and PKA- and MAPK-dependent post-receptor intracellular signalling cascades; (3) to identify the active part of the 28-amino acid molecule responsible for the effects of ghrelin on ovarian cells. We compared the effect of full-length ghrelin 1-28, a synthetic activator of GHS-R1a, GHRP6, and ghrelin molecular fragments 1-18 and 1-5 on cultured chicken ovarian cells. Indices of cell apoptosis (expression of the apoptotic peptide bax and the anti-apoptotic peptide bcl-2), proliferation (expression of proliferation-associated peptide PCNA), and expression of protein kinases (PKA and MAPK) within ovarian granulosa cells were analysed by immunocytochemistry. The secretion of progesterone (P(4)), testosterone (T), estradiol (E(2)) and arginine-vasotocin (AVT) by isolated ovarian follicular fragments was evaluated by RIA/EIA. It was observed that accumulation of bax was increased by ghrelin 1-28, GHRP6 and ghrelin 1-18, but not by ghrelin 1-5. Expression of bcl-2 was suppressed by addition of ghrelin 1-28, GHRP6 and ghrelin 1-5, but promoted by ghrelin 1-18. The occurrence of PCNA was reduced by ghrelin 1-28, GHRP6, ghrelin 1-18 and ghrelin 1-5. An increase in the expression of MAPK/ERK1, 2 was observed after addition of ghrelin 1-28, GHRP6 and ghrelin 1-18, but not ghrelin 1-5. The accumulation of PKA decreased after treatment with ghrelin 1-28 and increased after treatment with GHRP6 and ghrelin 1-18 but not ghrelin 1-5. Secretion of P(4) by ovarian follicular fragments was decreased after addition of ghrelin 1-28 or ghrelin 1-5 but stimulated by GHRP6 and ghrelin 1-18. Testosterone secretion was inhibited by ghrelins 1-28 and 1-18, but not by GHRP6 or ghrelin 1-5. Estradiol secretion was reduced after treatment with ghrelin 1-28 but

  10. Antioxidant status and selected biochemical parameters of porcine ovarian granulosa cells exposed to lead in vitro.

    Science.gov (United States)

    Capcarová, Marcela; Kolesárová, Adriana; Lukác, Norbert; Sirotkin, Alexander; Roychoudhury, Shubhadeep

    2009-12-01

    The objective of this study was to determine the activity of superoxide dismutase (SOD), total antioxidant status (TAS) and release of calcium, phosphorus, magnesium, sodium, potassium, total lipids, totals proteins, glucose, cholesterol and triglycerides by porcine ovarian granulosa cells cultured in vitro after lead acetate administration. The parameters were analyzed using semi-automated clinical chemistry analyzer Microlab 300, microprocessor-controlled analyzer EasyLite and spectrophotometer Genesys 10. Cells were cultured with lead acetate trihydrate [Pb(CH(3)COO)(2).3H(2)O] as follows: group Max (5 mg Pb(CH(3)COO)(2).3H(2)O/10 mL), group A (2.5 mg/10 mL), group B (0.83 mg/10 mL), group C (0.625 mg/10 mL), group D (0.455 mg/10 mL) and the control group without lead exposure for 18 hrs. The highest TAS was estimated in the control group without lead treatment in comparison with other groups (MAX, A, B, C, D). Statistical analyses showed significantly lower value (P 0.05) were detected in concentration of other studied parameters among observed groups, too.

  11. Adult granulosa cell tumor associated with endometrial carcinoma: a case report

    Directory of Open Access Journals (Sweden)

    Eke Ahizechukwu C

    2011-08-01

    Full Text Available Abstract Introduction If strict criteria for the diagnosis of carcinoma are used and all patients with granulosa cell tumors are considered, the best estimate of the incidence of associated endometrial carcinomas is under 5%. In patients with granulosa cell tumors, estrogen-dependent endometrial cancers are rarely found, and most of these endometrial cancers are well-differentiated endometrioid adenocarcinomas that carry a good prognosis when detected early. Case presentation We report the case of a 65-year-old post-menopausal Nigerian woman of the Igbo tribe with an adult granulosa cell tumor that was initially treated as endometrial carcinoma. She underwent a total abdominal hysterectomy and a bilateral salpingo-oophorectomy after histopathologic confirmation of a well-differentiated granulosa cell tumor of the ovary and a nuclear grade 1 adenocarcinoma of the endometrium (International Federation of Obstetricians and Gynecologists stage 1B. She had a good post-operative recovery and was discharged 10 days after treatment. Conclusion The association between adult granulosa cell tumors of the ovary and endometrial carcinomas is rare. A high index of suspicion as well as good imaging and histopathologic analyses are important in making this diagnosis.

  12. Phosphoramide mustard exposure induces DNA adduct formation and the DNA damage repair response in rat ovarian granulosa cells

    Energy Technology Data Exchange (ETDEWEB)

    Ganesan, Shanthi, E-mail: shanthig@iastate.edu; Keating, Aileen F., E-mail: akeating@iastate.edu

    2015-02-01

    Phosphoramide mustard (PM), the ovotoxic metabolite of the anti-cancer agent cyclophosphamide (CPA), destroys rapidly dividing cells by forming NOR-G-OH, NOR-G and G-NOR-G adducts with DNA, potentially leading to DNA damage. A previous study demonstrated that PM induces ovarian DNA damage in rat ovaries. To investigate whether PM induces DNA adduct formation, DNA damage and induction of the DNA repair response, rat spontaneously immortalized granulosa cells (SIGCs) were treated with vehicle control (1% DMSO) or PM (3 or 6 μM) for 24 or 48 h. Cell viability was reduced (P < 0.05) after 48 h of exposure to 3 or 6 μM PM. The NOR-G-OH DNA adduct was detected after 24 h of 6 μM PM exposure, while the more cytotoxic G-NOR-G DNA adduct was formed after 48 h by exposure to both PM concentrations. Phosphorylated H2AX (γH2AX), a marker of DNA double stranded break occurrence, was also increased by PM exposure, coincident with DNA adduct formation. Additionally, induction of genes (Atm, Parp1, Prkdc, Xrcc6, and Brca1) and proteins (ATM, γH2AX, PARP-1, PRKDC, XRCC6, and BRCA1) involved in DNA repair were observed in both a time- and dose-dependent manner. These data support that PM induces DNA adduct formation in ovarian granulosa cells, induces DNA damage and elicits the ovarian DNA repair response. - Highlights: • PM forms ovarian DNA adducts. • DNA damage marker γH2AX increased by PM exposure. • PM induces ovarian DNA double strand break repair.

  13. Ultrastructure of the basal lamina of bovine ovarian follicles and its relationship to the membrana granulosa.

    Science.gov (United States)

    Irving-Rodgers, H F; Rodgers, R J

    2000-03-01

    Different morphological phenotypes of follicular basal lamina and of membrana granulosa have been observed. Ten preantral follicles (basal lamina and membrana granulosa. Within each antral follicle, the shape of the basal cells of the membrana granulosa was uniform, and either rounded or columnar. There were equal proportions of follicles basal cells and with rounded basal cells. Larger follicles had only rounded basal cells. Conventional basal laminae of a single layer adjacent to the basal granulosa cells were observed in healthy follicles at the preantral and antral stages. However, at the preantral stage, the conventional types of basal lamina were enlarged or even partially laminated. A second type of basal lamina, described as 'loopy', occurred in about half the preantral follicles and in half the antral follicles basal laminae were not observed in larger follicles. 'Loopy' basal laminae were composed of basal laminae aligning the basal surface of basal granulosa cells, but with additional layers or loops often branching from the innermost layer. Each loop was usually Basal cellular processes were also common, and vesicles could be seen budding off from these processes. In antral follicles, conventional basal laminae occurred in follicles with rounded basal granulosa cells. Other follicles with columnar cells, and atretic follicles, had the 'loopy' basal lamina phenotype. Thus, follicles have different basal laminae that relate to the morphology of the membrana granulosa. PMID:10864785

  14. Specific disruption of Tsc1 in ovarian granulosa cells promotes ovulation and causes progressive accumulation of corpora lutea.

    Directory of Open Access Journals (Sweden)

    Lin Huang

    Full Text Available Tuberous sclerosis complex 1 (Tsc1 is a tumor suppressor negatively regulating mammalian target of rapamycin complex 1 (mTORC1. It is reported that mice lacking Tsc1 gene in oocytes show depletion of primordial follicles, resulting in premature ovarian failure and subsequent infertility. A recent study indicated that deletion of Tsc1 in somatic cells of the reproductive tract caused infertility of female mice. However, it is not known whether specific disruption of Tsc1 in granulosa cells influences the reproductive activity of female mice. To clarify this problem, we mated Tsc1(flox/flox mice with transgenic mice strain expressing cyp19-cre which exclusively expresses in granulosa cells of the ovary. Our results demonstrated that Tsc1(flox/flox; cyp19-cre mutant mice were fertile, ovulating more oocytes and giving birth to more pups than control Tsc1(flox/flox mice. Progressive accumulation of corpora lutea occurred in the Tsc1(flox/flox; cyp19-cre mutant mice with advanced age. These phenotypes could be explained by the elevated activity of mTORC1, as indicated by increased phosphorylation of rpS6, a substrate of S6 in the Tsc1(flox/flox; cyp19-cre mutant granulosa cells. In addition, rapamycin, a specific mTORC1 inhibitor, effectively rescued the phenotype caused by increased mTORC1 activity in the Tsc1(cko ovaries. Our data suggest that conditional knockout of Tsc1 in granulosa cells promotes reproductive activity in mice.

  15. Evidence for ovarian granulosa stem cells: telomerase activity and localization of the telomerase ribonucleic acid component in bovine ovarian follicles.

    Science.gov (United States)

    Lavranos, T C; Mathis, J M; Latham, S E; Kalionis, B; Shay, J W; Rodgers, R J

    1999-08-01

    We have previously postulated that granulosa cells of developing follicles arise from a population of stem cells. Stem cells and cancer cells can divide indefinitely partly because they express telomerase. Telomerase is a ribonucleoprotein enzyme that repairs the ends of telomeres that otherwise shorten progressively upon each successive cell division. In this study we carried out cell cycle analyses and examined telomerase expression to examine our hypothesis. Preantral (60-100 microm) and small (1 mm) follicles, as well as granulosa cells from medium-sized (3 mm) and large (6-8 mm) follicles, were isolated. Cell cycle analyses and expression of Ki-67, a cell cycle-related protein, were undertaken on follicles of each size (n = 3) by flow cytometry; 12% to 16% of granulosa cells in all follicles were in the S phase, and less than 2% were in the G(2)/M phase. Telomerase activity (n = 3) was highest in the small preantral follicles, declining at the 1-mm stage and even further at the 3-mm stage. In situ hybridization histochemistry was carried out on bovine ovaries, and telomerase RNA was detected in the granulosa cells of growing follicles but not primordial follicles. Two major patterns of staining were observed in the membrana granulosa of antral follicles: staining in the middle and antral layers, and staining in the middle and basal layers. No staining was detected in oocytes. Our results strongly support our hypothesis that granulosa cells arise from a population of stem cells. PMID:10411512

  16. EVIDENCE FOR EXISTENCE OF IMMUNOGLOBULINS THAT BLOCK OVARIAN GRANULOSA-CELL GROWTH-INVITRO - A PUTATIVE ROLE IN RESISTANT OVARY SYNDROME

    NARCIS (Netherlands)

    VANWEISSENBRUCH, MM; HOEK, A; VAN VLIET BLEEKER, I.; SCHOEMAKER, J; DREXHAGE, H

    1991-01-01

    The sera of 26 patients with premature ovarian failure were examined in order to detect immunoglobulin-G (IgGs) that can block FSH-induced in vitro granulosa cell DNA synthesis via, a Feulgen cytochemical bioassay system. The IgGs of four patients with polycystic ovary-like disease, five postmenopau

  17. Circadian Clock genes Per2 and clock regulate steroid production, cell proliferation, and luteinizing hormone receptor transcription in ovarian granulosa cells

    Energy Technology Data Exchange (ETDEWEB)

    Shimizu, Takashi, E-mail: shimizut@obihiro.ac.jp [Graduate School of Animal and Food Hygiene, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555 (Japan); Hirai, Yuko; Murayama, Chiaki; Miyamoto, Akio [Graduate School of Animal and Food Hygiene, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555 (Japan); Miyazaki, Hitoshi [Gene Research Center, University of Tsukuba, Tsukuba, Ibaraki 305-8572 (Japan); Miyazaki, Koyomi [Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST) Central 6, 1-1-1, Higashi, Tsukuba, Ibaraki 305-8566 (Japan)

    2011-08-19

    Highlights: {yields} Treatment with Per2 and Clock siRNAs decreased the number of granulosa cells and LHr expression. {yields}Per2 siRNA treatment did not stimulate the production of estradiol and expression of P450arom. {yields} Clock siRNA treatment inhibited the production of estradiol and expression of P450arom mRNA. {yields}Per2 and Clock siRNA treatment increased and unchanged, respectively, progesterone production in FSH-treated granulosa cells. {yields} The expression of StAR mRNA was increased by Per2 siRNA and unchanged by Clock siRNA. -- Abstract: Circadian Clock genes are associated with the estrous cycle in female animals. Treatment with Per2 and Clock siRNAs decreased the number of granulosa cells and LHr expression in follicle-stimulating hormone FSH-treated granulosa cells. Per2 siRNA treatment did not stimulate the production of estradiol and expression of P450arom, whereas Clock siRNA treatment inhibited the production of estradiol and expression of P450arom mRNA. Per2 and Clock siRNA treatment increased and unchanged, respectively, progesterone production in FSH-treated granulosa cells. Similarly, expression of StAR mRNA was increased by Per2 siRNA and unchanged by Clock siRNA. Our data provide a new insight that Per2 and Clock have different action on ovarian granulosa cell functions.

  18. Growth Hormone Releasing Peptide-2 Attenuation of Protein Kinase C-Induced Inflammation in Human Ovarian Granulosa Cells

    Science.gov (United States)

    Chao, Yi-Ning; Sun, David; Peng, Yen-Chun; Wu, Yuh-Lin

    2016-01-01

    Cyclooxygenase-2 (COX-2) and interleukin-8 (IL-8) are two important inflammatory mediators in ovulation. Ghrelin may modulate inflammatory signaling via growth hormone secretagogue receptors. We investigated the role of ghrelin in KGN human ovarian granulosa cells using protein kinase C (PKC) activator phorbol 12, 13-didecanoate (PDD) and synthetic ghrelin analog growth hormone releasing peptide-2 (GHRP-2). GHRP-2 attenuated PDD-induced expression of protein and mRNA, the promoter activity of COX-2 and IL-8 genes, and the secretion of prostaglandin E2 (PGE2) and IL-8. GHRP-2 promoted the degradation of PDD-induced COX-2 and IL-8 proteins with the involvement of proteasomal and lysosomal pathways. PDD-mediated COX-2 production acts via the p38, c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways; PDD-mediated IL-8 production acts via the p38, JNK and ERK pathways. GHRP-2 reduced the PDD-induced phosphorylation of p38 and JNK and activator protein 1 (AP-1) reporter activation and PDD-induced NF-κB nuclear translocation and reporter activation. The inhibitors of mitogen-activated protein kinase phosphatase-1 (MKP-1) and protein phosphatase 2 (PP2A) reduced the inhibitory effect of GHRP-2 on PDD-induced COX-2 and IL-8 expression. Our findings demonstrate an anti-inflammatory role for ghrelin (GHRP-2) in PKC-mediated inflammation of granulosa cells, at least in part, due to its inhibitory effect on PKC-induced activation of p38, JNK and NF-κB, possibly by targeting to MKP-1 and PP2A. PMID:27548147

  19. Diagnosis and treatment of ovarian granulosa cell tumors%卵巢粒层细胞瘤的诊治

    Institute of Scientific and Technical Information of China (English)

    邓继华; 尤勇

    2013-01-01

    目的 探讨卵巢粒层细胞瘤的临床表现及辅助检查特点、诊断及治疗要点,以提高对该肿瘤的诊治水平.方法 收集大竹县人民医院1995年3月至2009年5月经病理学确诊为卵巢粒层细胞瘤的13例患者的临床资料,总结分析其临床、影像、病理特点.结果 13例患者年龄47 ~68岁(平均53岁),临床表现为月经异常或绝经后阴道出血2d~7个月余,伴或不伴腹胀腹痛.术中见肿决位于盆腔卵巢,活动度尚可,表面光滑或微突结节状.超声及CT提示囊实性混合性肿块.病理特征为细胞核有核沟呈咖啡豆样外观,且围绕嗜酸性物质排列成Call-Exner小体结构.免疫组化可表达CD99、inhibin、calretinin、Vimentin.经手术治疗并辅以化疗,12例成人型患者5年、10年生存率分别为100%、91.7%.结论 卵巢粒层细胞瘤是好发于中老年女性的低度恶性肿瘤,临床多表现为月经异常或绝经后阴道出血,其诊断主要靠病理学,治疗以手术为主,辅以化疗,预后较好.掌握上述各特征,施以恰当治疗并长期随访有重要临床意义.%Objective To investigate the clinical and pathological features and auxiliary examination of ovarian granulosa cell tumors,and to improve the diagnostic and therapeutic levels.Methods The clinical data of 13 cases who were diagnosed by pathology in Dazhu people's hospital from March 1995 to May 2009 were collected and their clinical findings,image shows and pathlogical features were analyzed.Results The patients were 47 to 75 years old(mean 53 years old),and their clinical manefestations were abnormal menstruation or postmenopause vaginal bleeding for 2 days to 7 months and some patients were complicated with abdominal distention and stomachache.The tumors located in the ovarium with mobility and their surface were smooth or with small nodosity.Their imagings on the ultrosound and CT showed cystica-solid mixed tumors.The nuclear grooves made the nuclei like

  20. Autocrine/paracrine proliferative effect of ovarian GH and IGF-I in chicken granulosa cell cultures.

    Science.gov (United States)

    Ahumada-Solórzano, S Marisela; Martínez-Moreno, Carlos G; Carranza, Martha; Ávila-Mendoza, José; Luna-Acosta, José Luis; Harvey, Steve; Luna, Maricela; Arámburo, Carlos

    2016-08-01

    It is known that growth hormone (GH) and its receptor (GHR) are expressed in granulosa cells (GC) and thecal cells during the follicular development in the hen ovary, which suggests GH is involved in autocrine/paracrine actions in the female reproductive system. In this work, we show that the knockdown of local ovarian GH with a specific cGH siRNA in GC cultures significantly decreased both cGH mRNA expression and GH secretion to the media, and also reduced their proliferative rate. Thus, we analyzed the effect of ovarian GH and recombinant chicken GH (rcGH) on the proliferation of pre-hierarchical GCs in primary cultures. Incubation of GCs with either rcGH or conditioned media, containing predominantly a 15-kDa GH isoform, showed that both significantly increased proliferation as determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, proliferating cell nuclear antigen (PCNA) quantification and ((3)H)-thymidine incorporation ((3)H-T) assays in a dose response fashion. Both, locally produced GH and rcGH also induced the phosphorylation of Erk1/2 in GC cultures. Furthermore, GH increased IGF-I synthesis and its release into the GC culture incubation media. These results suggest that GH may act through local IGF-I to induce GC proliferation, since IGF-I immunoneutralization completely abolished the GH-induced proliferative effect. These data suggest that GH and IGF-I may play a role as autocrine/paracrine regulators during the follicular development in the hen ovary at the pre-hierarchical stage. PMID:27174747

  1. Androgen receptor and miRNA-126* axis controls follicle-stimulating hormone receptor expression in porcine ovarian granulosa cells.

    Science.gov (United States)

    Du, Xing; Li, Qiqi; Pan, Zengxiang; Li, Qifa

    2016-08-01

    Androgen, which acts via the androgen receptor (AR), plays crucial roles in mammalian ovarian function. Recent studies showed that androgen/AR signaling regulates follicle-stimulating hormone receptor (FSHR) expression in follicles; however, the detailed mechanism underlying this regulation remained unknown. Here, we demonstrate that AR and miR-126* cooperate to inhibit FSHR expression and function in pig follicular granulosa cells (pGCs). In pGCs, overexpression of AR decreased, whereas knockdown increased, FSHR mRNA and protein expression; however, neither manipulation affected FSHR promoter activity. Using a dual-luciferase reporter assay, we found that the FSHR gene is a direct target of miR-126*, which inhibits FSHR expression and increases the rate of AR-induced apoptosis in pGCs. Collectively, our data show for the first time that the AR/miR-126* axis exerts synergetic effects in the regulation of FSHR expression and apoptosis in pGCs. Our findings thus define a novel pathway, AR/miR-126*/FSHR, that regulates mammalian GC functions. PMID:27222597

  2. Differences in gene expression of granulosa cells from women undergoing controlled ovarian hyperstimulation with either recombinant follicle-stimulating hormone or highly purified human menopausal gonadotropin

    DEFF Research Database (Denmark)

    Grøndahl, Marie Louise; Borup, Rehannah; Lee, Young Bae;

    2009-01-01

    OBJECTIVE: To investigate the differences in the gene expression profile of granulosa cells from preovulatory follicles after controlled ovarian hyperstimulation (COH) with recombinant follicle-stimulating hormone (FSH) or urinary human menopausal gonadotropin (hMG) FSH. DESIGN: Prospective...... randomized study. SETTING: University-based facilities for clinical services and research. PATIENT(S): Thirty women undergoing treatment with vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). INTERVENTION(S): Patients were randomly allocated to receive recombinant FSH or human (hMG) COH....... Granulosa cells were collected from follicular fluid after oocyte retrieval, and mRNA were isolated for gene expression analysis. MAIN OUTCOME MEASURE(S): General gene expression profile. RESULT(S): Ninety-six probe sets (85 genes) showed statistically significant differences in expression level in the two...

  3. Expression of antiapoptosis gene survivin in luteinized ovarian granulosa cells of women undergoing IVF or ICSI and embryo transfer: clinical correlations

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    Varras Michail

    2012-09-01

    Full Text Available Abstract Background The purpose of the study was to determine the incidence of survivin gene expression in human granulosa cells during ovarian stimulation in Greek women with normal FSH levels, undergoing IVF or ICSI and to discover any correlation between levels of gene expression and clinical parameters, efficacy of ovulation or outcomes of assisted reproduction. Methods Twenty nine women underwent ovulation induction for IVF or ICSI and ET with standard GnRH analogue-recombinant FSH protocol. Infertility causes were male and tubal factor. Cumulus–mature oocyte complexes were denuded and the granulosa cells were analyzed for each patient separately using quantitative reverse transcription polymerase chain reaction analysis for survivin gene expression with internal standard the ABL gene. Results The ABL and survivin mRNA were detected in granulosa cells in 93.1%. The expression levels of survivin were significantly lower in normal women (male infertility factor compared to women with tubal infertility factor (p = 0.007. There was no additional statistically significant correlation between levels of survivin expression and estradiol levels or dosage of FSH for ovulation induction or number of dominant follicles aspirated or number of retrieved oocytes or embryo grade or clinical pregnancy rates respectively. Conclusions High levels of survivin mRNA expression in luteinized granulosa cells in cases with tubal infertility seem to protect ovaries from follicular apoptosis. A subpopulation of patients with low levels of survivin mRNA in granulosa cells might benefit with ICSI treatment to bypass possible natural barriers of sperm-oocyte interactions.

  4. Impact of apigenin on ovarian granulosa cell apoptosis in female rats%芹菜素对雌性大鼠卵巢颗粒细胞凋亡影响

    Institute of Scientific and Technical Information of China (English)

    李伟红; 周丰; 庄笑梅; 姜恩魁; 姜岩

    2011-01-01

    目的 探讨芹菜素(apigenin,Api)对大鼠卵巢颗粒细胞凋亡的影响.方法 选情前期成年雌性SD大鼠20只,取卵巢颗粒细胞进行原代细菌培养,贴壁后随机分为4组(对照组、Api 10-4M组、Api 10-5M组、Api 10-6M组),加入处理因素.培养结束后,收集各组培养卵巢颗粒细胞,经苏木精-伊红染色和吖啶橙染色观察颗粒细胞形态,经MTT法及流式细胞仪检测颗粒细胞凋亡率,观察Api对大鼠卵巢颗粒细胞凋亡的影响.结果 MTT法检测对照组,Api 10-4M组、Api 10-5M组、Api 10-6M组A值分别为(0.87±0.059)、(0.29±0.057)(0.49±0.03)、(0.63±0.035);实验组与对照组比较差异有统计学意义(P<0.01),提示实验组颗粒细胞数量减少,出现凋亡细胞;流式细胞仪检测对月强组、Api 10-4M组、Api 10-5M组、Api 10-6M组的颗粒细胞凋亡率分别为(3.63±0.37)%、(36.37±2.28)%、(34.67±1.96)%、(30.92±1.65)%,实验组与对照组比较差异有统计学意义(P<0.01),提示实验组颗粒细胞凋亡率明显增高.结论 Api能抑制卵巢颗粒细胞的增殖,并促进其凋亡.%Objective To investigate the impact of apigenin(Api) on ovarian granulosa cell apoptosis in female rats.Methods Twenty adult female proestrus SD rats were selected and their granulosa cells were treated with primary cell culture. After adherence, the cells were randomly divided into four groups (control group, groups treated with 10-4M, 10-5 M, and 10-6M of Api ). After the treatment, all ovarian granulosa cells were gathered and stained with heamatoxylin-eosin (HE) and acridine orange(AO) to observe the form of granulosa cell. Granulosa cell apoptosis rate was detected by methyl thiazolyl tetrazolium(MTT) assay and flow cytometry to observe the effect of Api on apoptosis of ovarian granulosa cell.Results The A values for the control,10 -4M,10 -5M,and 10-6M Api groups were 0. 87 ±0. 059,0. 29 ±0. 057,0. 49 ±0. 03,and 0. 63 ± 0. 035, respectively, with significant

  5. Resveratrol promotes expression of SIRT1 and StAR in rat ovarian granulosa cells: an implicative role of SIRT1 in the ovary

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    Morita Yoshihiro

    2012-02-01

    Full Text Available Abstract Background Resveratrol is a natural polyphenolic compound known for its beneficial effects on energy homeostasis, and it also has multiple properties, including anti-oxidant, anti-inflammatory, and anti-tumor activities. Recently, silent information regulator genes (Sirtuins have been identified as targets of resveratrol. Sirtuin 1 (SIRT1, originally found as an NAD+-dependent histone deacetylase, is a principal modulator of pathways downstream of calorie restriction, and the activation of SIRT1 ameliorates glucose homeostasis and insulin sensitivity. To date, the presence and physiological role of SIRT1 in the ovary are not known. Here we found that SIRT1 was localized in granulosa cells of the human ovary. Methods The physiological roles of resveratrol and SIRT1 in the ovary were analyzed. Immunohistochemistry was performed to localize the SIRT1 expression. SIRT1 protein expression of cultured cells and luteinized human granulosa cells was investigated by Western blot. Rat granulosa cells were obtained from diethylstilbestrol treated rats. The cells were treated with increasing doses of resveratrol, and subsequently harvested to determine mRNA levels and protein levels. Cell viability was tested by MTS assay. Cellular apoptosis was analyzed by caspase 3/7 activity test and Hoechst 33342 staining. Results SIRT1 protein was expressed in the human ovarian tissues and human luteinized granulosa cells. We demonstrated that resveratrol exhibited a potent concentration-dependent inhibition of rat granulosa cells viability. However, resveratrol-induced inhibition of rat granulosa cells viability is independent of apoptosis signal. Resveratrol increased mRNA levels of SIRT1, LH receptor, StAR, and P450 aromatase, while mRNA levels of FSH receptor remained unchanged. Western blot analysis was consistent with the results of quantitative real-time RT-PCR assay. In addition, progesterone secretion was induced by the treatment of resveratrol

  6. Juvenile granulosa cell tumour: a rare clinical entity

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    Kaliki Hymavathi Reddy

    2014-08-01

    Full Text Available Ovarian cancer is the third most common neoplasm of the female genital tract. Based on the cell type of origin, primary ovarian malignancies are classified into surface epithelium, germ cell, and sex cord tumors. Sex cord tumors account for 1% to 2% of ovarian malignancies. They may contain granulosa cells, theca cells, sertoli cells, or fibroblasts of gonadal stromal origin. Granulosa Cell Tumours (GCTs account for approximately 2-5% of all ovarian tumors and can be divided into adult (95% and juvenile (5% types based on histologic findings. GCTs secrete estrogen thus resulting in menstrual irregularities in the affected individual. More serious estrogen effects can occur in various end organs such as uterus resulting in endometrial hyperplasia, endometrial adenocarcinomas and increased risk of breast cancers. Androgen production is also reported but rare and produces virilization in the affected women. Juvenile Granulosa Cell Tumours (JGCTs are clinically and histopathologically distinct from the GCTs. They are rarely encountered but mostly in youngsters. Surgery is the primary modality of treatment with chemotherapy being reserved for advanced or recurrent disease states. We herewith report an interesting case of JGCT in a young teenage girl. [Int J Reprod Contracept Obstet Gynecol 2014; 3(4.000: 1150-1154

  7. Novel effects of the cyclooxygenase-2-selective inhibitor NS-398 on IL-1β-induced cyclooxygenase-2 and IL-8 expression in human ovarian granulosa cells.

    Science.gov (United States)

    Ou, Hui-Ling; Sun, David; Peng, Yen-Chun; Wu, Yuh-Lin

    2016-08-01

    Ovulation is a critical inflammation-like event that is central to ovarian physiology. IL-1β is an immediate early pro-inflammatory cytokine that regulates production of several other inflammatory mediators, such as cyclooxygenase 2 (COX)-2 and IL-8. NS-398 is a selective inhibitor of COX-2 bioactivity and thus this drug is able to mitigate the COX-2-mediated production of downstream prostaglandins and the subsequent inflammatory response. Here we have investigated the action of NS-398 using a human ovarian granulosa cell line, KGN, by exploring IL-1β-regulated COX-2 and IL-8 expression. First, NS-398, instead of reducing inflammation, appeared to further enhance IL-1β-mediated COX-2 and IL-8 production. Using selective inhibitors targeting various signaling molecules, MAPK and NF-κB pathways both seemed to be involved in the impact of NS-398 on IL-1β-induced COX-2 and IL-8 expression. NS-398 also promoted IL-1β-mediated NF-κB p65 nuclear translocation but had no effect on IL-1β-activated MAPK phosphorylation. Flow cytometry analysis demonstrated that NS-398, in combination with IL-1β, significantly enhanced cell cycle progression involving IL-8. Our findings demonstrate a clear pro-inflammatory function for NS-398 in the IL-1β-mediated inflammatory response of granulosa cells, at least in part, owing to its augmenting effect on the IL-1β-induced activation of NF-κB. PMID:27312705

  8. Efficient differentiation of steroidogenic and germ-like cells from epigenetically-related iPSCs derived from ovarian granulosa cells.

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    Raymond Anchan

    Full Text Available To explore restoration of ovarian function using epigenetically-related, induced pluripotent stem cells (iPSCs, we functionally evaluated the epigenetic memory of novel iPSC lines, derived from mouse and human ovarian granulosa cells (GCs using c-Myc, Klf4, Sox2 and Oct4 retroviral vectors. The stem cell identity of the mouse and human GC-derived iPSCs (mGriPSCs, hGriPSCs was verified by demonstrating embryonic stem cell (ESC antigen expression using immunocytochemistry and RT-PCR analysis, as well as formation of embryoid bodies (EBs and teratomas that are capable of differentiating into cells from all three germ layers. GriPSCs' gene expression profiles associate more closely with those of ESCs than of the originating GCs as demonstrated by genome-wide analysis of mRNA and microRNA. A comparative analysis of EBs generated from three different mouse cell lines (mGriPSCs; fibroblast-derived iPSC, mFiPSCs; G4 embryonic stem cells, G4 mESCs revealed that differentiated mGriPSC-EBs synthesize 10-fold more estradiol (E2 than either differentiated FiPSC- or mESC-EBs under identical culture conditions. By contrast, mESC-EBs primarily synthesize progesterone (P4 and FiPSC-EBs produce neither E2 nor P4. Differentiated mGriPSC-EBs also express ovarian markers (AMHR, FSHR, Cyp19a1, ER and Inha as well as markers of early gametogenesis (Mvh, Dazl, Gdf9, Boule and Zp1 more frequently than EBs of the other cell lines. These results provide evidence of preferential homotypic differentiation of mGriPSCs into ovarian cell types. Collectively, our data support the hypothesis that generating iPSCs from the desired tissue type may prove advantageous due to the iPSCs' epigenetic memory.

  9. Menoprogen, a TCM Herbal Formula for Menopause, Increases Endogenous E2 in an Aged Rat Model of Menopause by Reducing Ovarian Granulosa Cell Apoptosis

    Science.gov (United States)

    Li, Yu; Ma, Hong; Lu, Ye; Tan, B. J.; Xu, L.; Lawal, Temitope O.; Mahady, Gail B.; Liu, Daniel

    2016-01-01

    The effect of Menoprogen (MPG) on ovarian granulosa cell (GC) apoptosis was investigated in vitro and in vivo in an aged rat model of menopause. Intragastric administration of Menoprogen or estradiol valerate to 14-month-old senile female rats for eight weeks increased plasma E2 levels, as well as the weight of both ovarian and uterine tissues. Flow cytometric (FCM) analysis of isolated GCs from MPG-treated aged rats showed reductions in the G0/G1 ratio and apoptotic peaks. Isolated GCs also exhibited an increase in cell size and the number of cytoplastic organelles and intracellular gap junctions, the reappearance of secretory granules, and a lack of apoptotic bodies as determined by TEM. Results from a TdT-mediated dUTP nick end-labeling (TUNEL) assay revealed a reduction in TUNEL-positive GCs after MPG treatment. Immunohistochemical analysis showed a downregulation of proapoptotic Bax proteins and an upregulation of antiapoptotic Bcl-2 proteins. The addition of MPG-medicated serum to the media of cultured GCs also reduced cadmium chloride-induced apoptosis and downregulated caspase-3 protein expression. This work demonstrates that Menoprogen inhibits GC apoptosis in aged female rats and thereby increases E2 production. This represents a novel mechanism of action for this herbal medicine in the treatment of menopausal symptoms. PMID:26981526

  10. Menoprogen, a TCM Herbal Formula for Menopause, Increases Endogenous E2 in an Aged Rat Model of Menopause by Reducing Ovarian Granulosa Cell Apoptosis

    Directory of Open Access Journals (Sweden)

    Yu Li

    2016-01-01

    Full Text Available The effect of Menoprogen (MPG on ovarian granulosa cell (GC apoptosis was investigated in vitro and in vivo in an aged rat model of menopause. Intragastric administration of Menoprogen or estradiol valerate to 14-month-old senile female rats for eight weeks increased plasma E2 levels, as well as the weight of both ovarian and uterine tissues. Flow cytometric (FCM analysis of isolated GCs from MPG-treated aged rats showed reductions in the G0/G1 ratio and apoptotic peaks. Isolated GCs also exhibited an increase in cell size and the number of cytoplastic organelles and intracellular gap junctions, the reappearance of secretory granules, and a lack of apoptotic bodies as determined by TEM. Results from a TdT-mediated dUTP nick end-labeling (TUNEL assay revealed a reduction in TUNEL-positive GCs after MPG treatment. Immunohistochemical analysis showed a downregulation of proapoptotic Bax proteins and an upregulation of antiapoptotic Bcl-2 proteins. The addition of MPG-medicated serum to the media of cultured GCs also reduced cadmium chloride-induced apoptosis and downregulated caspase-3 protein expression. This work demonstrates that Menoprogen inhibits GC apoptosis in aged female rats and thereby increases E2 production. This represents a novel mechanism of action for this herbal medicine in the treatment of menopausal symptoms.

  11. The methoxychlor metabolite, 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane, inhibits steroidogenesis in rat ovarian granulosa cells in vitro.

    Science.gov (United States)

    Zachow, Rob; Uzumcu, Mehmet

    2006-11-01

    The exquisitely balanced hormonal mechanisms that control female fertility can be affected by several internal and external factors including pathogens, genetic maladies, and environmental agents. In the latter group are natural and synthetic agents known as endocrine disruptors. One such compound, 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), is the predominant metabolite of the pesticide methoxychlor. The effects of HPTE on ovarian steroidogenesis have not been previously reported and were investigated in the present study. Granulosa cells harvested from immature rats were treated with follicle-stimulating hormone (FSH) or N(6),2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (db-cAMP) in the presence or absence of HPTE. After 48h, progesterone (P4) and estradiol-17beta (E2) concentrations were measured in the culture media. Steady-state levels of the mRNAs encoding steroidogenic acute regulatory protein (StAR), P450 side-chain cleavage (P450scc), 3beta-hydroxysteroid dehydrogenase type 1 (3beta-HSD), and P450 aromatase (P450arom) were examined using real-time PCR. Both FSH- and db-cAMP-stimulated P(4) accumulation were impaired by HPTE. In contrast, FSH-, but not db-cAMP-stimulated, E2 content was suppressed by HPTE. The FSH-dependent increase in the abundance of P450scc, 3beta-HSD, and P450arom mRNAs was blocked by HPTE; however, StAR expression was not altered. Although db-cAMP-dependent P450arom was moderately reduced by HPTE, the levels of db-cAMP-dependent StAR, P450scc, and 3beta-HSD mRNAs were increased in the presence of HPTE. These data collectively show that HPTE can disrupt P4 and E2 production in granulosa cells, with implications for sites of action both preceding and following the generation of cAMP. The steroid-modulatory effects of HPTE in granulosa cells appear to involve the general suppression of the FSH-dependent expression of mRNAs encoding steroid pathway proteins, whereas the disparate effects of HPTE on cAMP-dependent m

  12. Differential gene expression in human granulosa cells from recombinant FSH versus human menopausal gonadotropin ovarian stimulation protocols

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    Bietz Mandi G

    2010-03-01

    Full Text Available Abstract Background The study was designed to test the hypothesis that granulosa cell (GC gene expression response differs between recombinant FSH and human menopausal gonadotropin (hMG stimulation regimens. Methods Females Results After exclusions, 1736 genes exhibited differential expression between groups. Over 400 were categorized as signal transduction genes, ~180 as transcriptional regulators, and ~175 as enzymes/metabolic genes. Expression of selected genes was confirmed by RT-PCR. Differentially expressed genes included A kinase anchor protein 11 (AKAP11, bone morphogenetic protein receptor II (BMPR2, epidermal growth factor (EGF, insulin-like growth factor binding protein (IGFBP-4, IGFBP-5, and hypoxia-inducible factor (HIF-1 alpha. Conclusions Results suggest that major differences exist in the mechanism by which pure FSH alone versus FSH/LH regulate gene expression in preovulatory GC that could impact oocyte maturity and developmental competence.

  13. Hedgehog signaling pathway in small bovine ovarian follicles

    Science.gov (United States)

    The hedgehog signaling pathway is involved in the regulation of cell proliferation, differentiation, and turnover in a variety of mammalian embryonic and adult tissues including bovine ovarian granulosa and theca cells. Binding of hedgehog to the patch receptor derepresses smoothened resulting in t...

  14. Vascular endothelial growth factor induces anti‑Müllerian hormone receptor 2 overexpression in ovarian granulosa cells of in vitro fertilization/intracytoplasmic sperm injection patients.

    Science.gov (United States)

    Fang, Yanqiu; Lu, Xiaodan; Liu, Lei; Lin, Xiuying; Sun, Munan; Fu, Jianhua; Xu, Shufen; Tan, Yan

    2016-06-01

    Misregulation of vascular endothelial growth factor A (VEGF‑A) has been implicated in numerous types of ovarian disease, such as polycystic ovarian syndrome, ovarian hyperstimulation syndrome, endometriosis and ovarian cancer. VEGF regulates blood vessel permeability and angiogenesis. In our previous study, VEGF‑regulated gene expression was profiled in the uterus of a transgenic mouse model with repressed VEGF expression, which indicated that VEGF is an important regulator in controlling gene expression in the uterus. The anti‑Müllerian hormone (AMH) is expressed by ovarian granulosa cells (GCs) and acts through its type 2 receptor, AMH receptor 2 (AMHR2). Serum AMH levels are used to predict ovarian reserves and the small antral follicles contribute markedly to the serum AMH level. AMH recruits primordial follicles and inhibits excessive follicular development by follicular stimulating hormone (FSH). However, AMH may be influenced by suppression of gonadotrophin secretion and VEGF inhibition. In the current study, human primary ovarian GCs were isolated from ovarian follicle fluid of in vitro fertilization/intracytoplasmic sperm injection cycles (IVF/ICSI). It was identified that the FSH receptor was consistently expressed in the isolated cells. VEGF‑A treatment stimulated AMHR2 overexpression at the gene and protein levels. In addition, VEGF induced AMHR2 expression on the surface of the isolated GCs from mature follicles. The VEGF treatment was also performed in an ovarian granulosa‑like cell line, KGN. AMH and AMHR2 are co‑expressed in normal GCs; however, as a result of VEGF misregulation, AMHR2 overexpression increases AMH binding, which may attenuate follicular or oocyte maturation. However, the associated function and underlying mechanism requires further investigation. PMID:27109000

  15. Regulation of MicroRNAs, and the Correlations of MicroRNAs and Their Targeted Genes by Zinc Oxide Nanoparticles in Ovarian Granulosa Cells.

    Science.gov (United States)

    Zhao, Yong; Li, Lan; Min, Ling-Jiang; Zhu, Lian-Qin; Sun, Qing-Yuan; Zhang, Hong-Fu; Liu, Xin-Qi; Zhang, Wei-Dong; Ge, Wei; Wang, Jun-Jie; Liu, Jing-Cai; Hao, Zhi-Hui

    2016-01-01

    Zinc oxide (ZnO) nanoparticles (NPs) have been applied in numerous industrial products and personal care products like sunscreens and cosmetics. The released ZnO NPs from consumer and household products into the environment might pose potential health issues for animals and humans. In this study the expression of microRNAs and the correlations of microRNAs and their targeted genes in ZnO NPs treated chicken ovarian granulosa cells were investigated. ZnSO4 was used as the sole Zn2+ provider to differentiate the effects of NPs from Zn2+. It was found that ZnO-NP-5 μg/ml specifically regulated the expression of microRNAs involved in embryonic development although ZnO-NP-5 μg/ml and ZnSO4-10 μg/ml treatments produced the same intracellular Zn concentrations and resulted in similar cell growth inhibition. And ZnO-NP-5 μg/ml also specifically regulated the correlations of microRNAs and their targeted genes. This is the first investigation that intact NPs in ZnO-NP-5 μg/ml treatment specifically regulated the expression of microRNAs, and the correlations of microRNAs and their targeted genes compared to that by Zn2+. This expands our knowledge for biological effects of ZnO NPs and at the same time it raises the health concerns that ZnO NPs might adversely affect our biological systems, even the reproductive systems through regulation of specific signaling pathways. PMID:27196542

  16. Regulation of MicroRNAs, and the Correlations of MicroRNAs and Their Targeted Genes by Zinc Oxide Nanoparticles in Ovarian Granulosa Cells.

    Directory of Open Access Journals (Sweden)

    Yong Zhao

    Full Text Available Zinc oxide (ZnO nanoparticles (NPs have been applied in numerous industrial products and personal care products like sunscreens and cosmetics. The released ZnO NPs from consumer and household products into the environment might pose potential health issues for animals and humans. In this study the expression of microRNAs and the correlations of microRNAs and their targeted genes in ZnO NPs treated chicken ovarian granulosa cells were investigated. ZnSO4 was used as the sole Zn2+ provider to differentiate the effects of NPs from Zn2+. It was found that ZnO-NP-5 μg/ml specifically regulated the expression of microRNAs involved in embryonic development although ZnO-NP-5 μg/ml and ZnSO4-10 μg/ml treatments produced the same intracellular Zn concentrations and resulted in similar cell growth inhibition. And ZnO-NP-5 μg/ml also specifically regulated the correlations of microRNAs and their targeted genes. This is the first investigation that intact NPs in ZnO-NP-5 μg/ml treatment specifically regulated the expression of microRNAs, and the correlations of microRNAs and their targeted genes compared to that by Zn2+. This expands our knowledge for biological effects of ZnO NPs and at the same time it raises the health concerns that ZnO NPs might adversely affect our biological systems, even the reproductive systems through regulation of specific signaling pathways.

  17. Regulation of MicroRNAs, and the Correlations of MicroRNAs and Their Targeted Genes by Zinc Oxide Nanoparticles in Ovarian Granulosa Cells

    Science.gov (United States)

    Zhao, Yong; Li, Lan; Min, Ling-Jiang; Zhu, Lian-Qin; Sun, Qing-Yuan; Zhang, Hong-Fu; Liu, Xin-Qi; Zhang, Wei-Dong; Ge, Wei; Wang, Jun-Jie; Liu, Jing-Cai

    2016-01-01

    Zinc oxide (ZnO) nanoparticles (NPs) have been applied in numerous industrial products and personal care products like sunscreens and cosmetics. The released ZnO NPs from consumer and household products into the environment might pose potential health issues for animals and humans. In this study the expression of microRNAs and the correlations of microRNAs and their targeted genes in ZnO NPs treated chicken ovarian granulosa cells were investigated. ZnSO4 was used as the sole Zn2+ provider to differentiate the effects of NPs from Zn2+. It was found that ZnO-NP-5 μg/ml specifically regulated the expression of microRNAs involved in embryonic development although ZnO-NP-5 μg/ml and ZnSO4-10 μg/ml treatments produced the same intracellular Zn concentrations and resulted in similar cell growth inhibition. And ZnO-NP-5 μg/ml also specifically regulated the correlations of microRNAs and their targeted genes. This is the first investigation that intact NPs in ZnO-NP-5 μg/ml treatment specifically regulated the expression of microRNAs, and the correlations of microRNAs and their targeted genes compared to that by Zn2+. This expands our knowledge for biological effects of ZnO NPs and at the same time it raises the health concerns that ZnO NPs might adversely affect our biological systems, even the reproductive systems through regulation of specific signaling pathways. PMID:27196542

  18. Development of the ovarian follicular epithelium.

    Science.gov (United States)

    Rodgers, R J; Lavranos, T C; van Wezel, I L; Irving-Rodgers, H F

    1999-05-25

    A lot is known about the endocrine control of the development of ovarian follicles, but a key question now facing researchers is which molecular and cellular processes take part in control of follicular growth and development. The growth and development of ovarian follicles occurs postnatally and throughout adult life. In this review, we focus on the follicular epithelium (membrana granulosa) and its basal lamina. We discuss a model of how granulosa cells arise from a population of stem cells and then enter different lineages before differentiation. The structure of the epithelium at the antral stage of development is presented, and the effects that follicle growth has on the behavior of the granulosa cells are discussed. Finally, we discuss the evidence that during follicle development the follicular basal lamina changes in composition. This would be expected if the behavior of the granulosa cells changes, or if the permeability of the basal lamina changes. It will be evident that the follicular epithelium has similarities to other epithelia in the body, but that it is more dynamic, as gross changes occur during the course of follicle development. This basic information will be important for the development of future reproductive technologies in both humans and animals, and possibly for understanding polycystic ovarian syndrome in women. PMID:10411332

  19. Tissue localization of GM-CSF receptor in bovine ovarian follicles and its role on glucose uptake by mural granulosa cells.

    Science.gov (United States)

    Peralta, O A; Bucher, D; Angulo, C; Castro, M A; Ratto, M H; Concha, Il

    2016-07-01

    The granulocyte-macrophage colony stimulating factor (GM-CSF) is a multifunctional cytokine implicated in proliferation, differentiation, and activation of several cell types including those involved in hematopoiesis and reproduction. In the present study, the expression of the α- and β-subunit genes of GM-CSF receptor during follicular development in cattle was assessed. The spatial association of α- and β-subunits of GM-CSF with follicle stimulating hormone receptor (FSHR) and 3β-hydroxysteroid dehydrogenase (3β-HSD), and the temporal associations with gene expression of hexose transporters (GLUTs) in granulosa cells of cattle were also evaluated. The effect of GM-CSF on the functionality of hexose transporters was also determined in an in vitro primary culture of granulosa cells. The spatial association of subunits of the GM-CSF receptor with 3β-HSD and FSHR suggests a potential steroidogenic regulation of GM-CSF in granulosa cells. Immunodetection of GLUTs and uptake kinetic assays confirmed expression and functionality of these genes for hexose transporters in granulosa cells of cattle. Treatment of granulosa cells with GM-CSF, FSH or insulin- like growth factor-I (IGF-I) alone increased 2-deoxyglucose (DOG) or 3-0-methylglucose (OMG) uptake; however, when cells were treated with various combination of these factors there were no additive effect. Unexpectedly, the combination of GM-CSF and FSH decreased DOG uptake compared to FSH treatment alone. Thus, the expression pattern of GM-CSF receptor subunit genes during follicle development in cattle and promotion of DOG and OMG uptake in granulosa cells indicate a role for GM-CSF, FSH and/or IGF-I alone in regulating granulosa cell metabolic activity, specifically by promoting glucose uptake. PMID:27236376

  20. Disrupción de las uniones mediadas por caderinas. Su rol en la apoptosis de las células granulosas del ovario porcino Disruption of junctions mediated by cadherins. Role in apoptosis of porcine ovarian granulosa cells

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    DM Lombardo

    2010-06-01

    cuali y cuantitativamente por TUNEL e ICQ anti Bax.The normal physiology and the dynamics of the reproductive tissue depends in great measure of an appropriate contact cell to cell, which is mediated by proteins of the cadherins family, molecules Ca++ dependent such as the E and N Cadherin. In these circumstances, the atresia process for apoptosis of the granulosa cells (CG, it could be related with the loss of this cellular contacts. In this work, the objective was to establish the relationship among the loss of the contacts Ca++ dependent with the integrity and the apoptosis of the CG. Considering the importance of cadherin (E-CAM and N-CAM in the development and follicular atresia, which most of the follicles begin to degenerate in the early antral stage and considering the atresia as a stage-dependent process was raised identify and localize the expression of these molecules in the ovary of adult pig, trying to discriminate and relate the different stages of follicle genesis. En antral follicles, those cells with an apparent loss of integrity (lack of cohesion with neighboring cells or disaggregated antral cell layer, did not identify any other label for antibodies in question. In order to correlate the same process in vitro, the study model was a cellular primary culture of porcine CG obtained by aspiration of antrals follicles, which were treated with EGTA, to obtain the disruptión of the homophilic juntions. The treatments were made with EGTA 9 nM and 100 nM and without EGTA, both treatment at different times of induction 6, 12 and 24 hours. In each case, the apoptosis index (AI was determined by DAPI and TUNEL techniques. Also, was carried out a quantitative evaluation by analysis of images of the expression of Bax by inmuno cytochemical. To different concentration of the inductor, the treatments with serum demonstrated a bigger AI to 9 nM (1,27; 2,58 and 1,38 to 6, 12 and 24 hs respectively. The activation was significant in the treatments of 12 hs with serum

  1. Two natural products, trans-phytol and (22E)-ergosta-6,9,22-triene-3β,5α,8α-triol, inhibit the biosynthesis of estrogen in human ovarian granulosa cells by aromatase (CYP19)

    International Nuclear Information System (INIS)

    Aromatase is the only enzyme in vertebrates to catalyze the biosynthesis of estrogens. Although inhibitors of aromatase have been developed for the treatment of estrogen-dependent breast cancer, the whole-body inhibition of aromatase causes severe adverse effects. Thus, tissue-selective aromatase inhibitors are important for the treatment of estrogen-dependent cancers. In this study, 63 natural products with diverse structures were examined for their effects on estrogen biosynthesis in human ovarian granulosa-like KGN cells. Two compounds—trans-phytol (SA-20) and (22E)-ergosta-6,9,22-triene-3β,5α,8α-triol (SA-48)—were found to potently inhibit estrogen biosynthesis (IC50: 1 μM and 0.5 μM, respectively). Both compounds decreased aromatase mRNA and protein expression levels in KGN cells, but had no effect on the aromatase catalytic activity in aromatase-overexpressing HEK293A cells and recombinant expressed aromatase. The two compounds decreased the expression of aromatase promoter I.3/II. Neither compound affected intracellular cyclic AMP (cAMP) levels, but they inhibited the phosphorylation or protein expression of cAMP response element-binding protein (CREB). The effects of these two compounds on extracellular regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinases (MAPKs), and AKT/phosphoinositide 3-kinase (PI3K) pathway were examined. Inhibition of p38 MAPK could be the mechanism underpinning the actions of these compounds. Our results suggests that natural products structurally similar to SA-20 and SA-48 may be a new source of tissue-selective aromatase modulators, and that p38 MAPK is important in the basal control of aromatase in ovarian granulosa cells. SA-20 and SA-48 warrant further investigation as new pharmaceutical tools for the prevention and treatment of estrogen-dependent cancers. - Highlights: • Two natural products inhibited estrogen biosynthesis in human ovarian granulosa cells. • They inhibited

  2. Two natural products, trans-phytol and (22E)-ergosta-6,9,22-triene-3β,5α,8α-triol, inhibit the biosynthesis of estrogen in human ovarian granulosa cells by aromatase (CYP19)

    Energy Technology Data Exchange (ETDEWEB)

    Guo, Jiajia [Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu (China); Yuan, Yun [Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu (China); School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang (China); Lu, Danfeng; Du, Baowen [Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu (China); Xiong, Liang; Shi, Jiangong [State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing (China); Yang, Lijuan [Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu (China); Liu, Wanli [MOE Key Laboratory of Protein Science, School of Life Sciences, Tsinghua University, Beijing 100084 (China); Yuan, Xiaohong [School of Life Science and Engineering, Southwest University of Science and Technology, Mianyang (China); Zhang, Guolin, E-mail: zhanggl@cib.ac.cn [Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu (China); Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu (China); Wang, Fei, E-mail: wangfei@cib.ac.cn [Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu (China); Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu (China)

    2014-08-15

    Aromatase is the only enzyme in vertebrates to catalyze the biosynthesis of estrogens. Although inhibitors of aromatase have been developed for the treatment of estrogen-dependent breast cancer, the whole-body inhibition of aromatase causes severe adverse effects. Thus, tissue-selective aromatase inhibitors are important for the treatment of estrogen-dependent cancers. In this study, 63 natural products with diverse structures were examined for their effects on estrogen biosynthesis in human ovarian granulosa-like KGN cells. Two compounds—trans-phytol (SA-20) and (22E)-ergosta-6,9,22-triene-3β,5α,8α-triol (SA-48)—were found to potently inhibit estrogen biosynthesis (IC{sub 50}: 1 μM and 0.5 μM, respectively). Both compounds decreased aromatase mRNA and protein expression levels in KGN cells, but had no effect on the aromatase catalytic activity in aromatase-overexpressing HEK293A cells and recombinant expressed aromatase. The two compounds decreased the expression of aromatase promoter I.3/II. Neither compound affected intracellular cyclic AMP (cAMP) levels, but they inhibited the phosphorylation or protein expression of cAMP response element-binding protein (CREB). The effects of these two compounds on extracellular regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinases (MAPKs), and AKT/phosphoinositide 3-kinase (PI3K) pathway were examined. Inhibition of p38 MAPK could be the mechanism underpinning the actions of these compounds. Our results suggests that natural products structurally similar to SA-20 and SA-48 may be a new source of tissue-selective aromatase modulators, and that p38 MAPK is important in the basal control of aromatase in ovarian granulosa cells. SA-20 and SA-48 warrant further investigation as new pharmaceutical tools for the prevention and treatment of estrogen-dependent cancers. - Highlights: • Two natural products inhibited estrogen biosynthesis in human ovarian granulosa cells. • They

  3. Expression and localization of fibroblast growth factor (FGF) family in buffalo ovarian follicle during different stages of development and modulatory role of FGF2 on steroidogenesis and survival of cultured buffalo granulosa cells.

    Science.gov (United States)

    Mishra, S R; Thakur, N; Somal, A; Parmar, M S; Reshma, R; Rajesh, G; Yadav, V P; Bharti, M K; Bharati, Jaya; Paul, A; Chouhan, V S; Sharma, G T; Singh, G; Sarkar, M

    2016-10-01

    The present study investigated the expression and localization of FGF and its functional receptors in the follicle of buffalo and the treatment of FGF2 on mRNA expression of CYP19A1 (aromatase), PCNA, and BAX (BCL-2 associated X protein) in cultured buffalo granulosa cells (GCs). Follicles were classified into four groups based on size and E2 level in follicular fluid (FF): F1, 4-6mm diameter, E214mm, E2>180ng/ml. The qPCR studies revealed that the mRNA expression of FGF1, FGF2 and FGF7 were maximum (Pfamily members are expressed in a regulated manner in buffalo ovarian follicles during different stages of development where FGF2 may promote steroidogenesis and GC survival through autocrine and paracrine manner. PMID:27663377

  4. Effects of BMAL1-SIRT1-positive cycle on estrogen synthesis in human ovarian granulosa cells: an implicative role of BMAL1 in PCOS.

    Science.gov (United States)

    Zhang, Jiaou; Liu, Jiansheng; Zhu, Kai; Hong, Yan; Sun, Yun; Zhao, Xiaoming; Du, Yanzhi; Chen, Zi-Jiang

    2016-08-01

    Brain and muscle ARNT-like protein 1 (BMAL1) is necessary for fertility and has been found to be essential to follicle growth and steroidogenesis. Sirtuin1 (SIRT1) has been reported to interact with BMAL1 and function in a circadian manner. Evidence has shown that SIRT1 regulates aromatase expression in estrogen-producing cells. We aimed to ascertain if there is a relationship between polycystic ovary syndrome (PCOS) and BMAL1, and whether and how BMAL1 takes part in estrogen synthesis in human granulosa cells (hGCs). Twenty-four women diagnosed with PCOS and 24 healthy individuals undergoing assisted reproduction were studied. BMAL1 expression in their granulosa cells (GCs) was observed by quantitative real-time polymerase chain reaction (qRT-PCR). The level of expression in the PCOS group was lower than that of the group without PCOS (p PCOS. PMID:27117143

  5. Effects of BMAL1-SIRT1-positive cycle on estrogen synthesis in human ovarian granulosa cells: an implicative role of BMAL1 in PCOS.

    Science.gov (United States)

    Zhang, Jiaou; Liu, Jiansheng; Zhu, Kai; Hong, Yan; Sun, Yun; Zhao, Xiaoming; Du, Yanzhi; Chen, Zi-Jiang

    2016-08-01

    Brain and muscle ARNT-like protein 1 (BMAL1) is necessary for fertility and has been found to be essential to follicle growth and steroidogenesis. Sirtuin1 (SIRT1) has been reported to interact with BMAL1 and function in a circadian manner. Evidence has shown that SIRT1 regulates aromatase expression in estrogen-producing cells. We aimed to ascertain if there is a relationship between polycystic ovary syndrome (PCOS) and BMAL1, and whether and how BMAL1 takes part in estrogen synthesis in human granulosa cells (hGCs). Twenty-four women diagnosed with PCOS and 24 healthy individuals undergoing assisted reproduction were studied. BMAL1 expression in their granulosa cells (GCs) was observed by quantitative real-time polymerase chain reaction (qRT-PCR). The level of expression in the PCOS group was lower than that of the group without PCOS (p PCOS.

  6. Clinicopathological aspects and their relation to prognosis in adult-type granulosa cell tumor of the ovary Aspectos clinicopatológicos e sua relação com o prognóstico em tumor de células da granulosa do tipo adulto do ovário

    Directory of Open Access Journals (Sweden)

    Maurício De Angelo Andrade

    2009-10-01

    Full Text Available INTRODUCTION AND OBJECTIVE: The adult granulosa cell tumors (AGCT correspond to less than 5% of ovarian neoplasias. They are considered low malignant potential tumors and may recur after many years. The differential diagnosis must be made with other primary or metastatic ovarian neoplasias. The aim was to analyze clinical and pathological aspects of AGCT and relate them to its evolution. METHOD: in a 10- year (1995-2004 review of the files from University of Campinas Clinical Hospital, Brazil, 20 AGCT cases were found. The clinical records and slides were reviewed and age, symptoms, macro and microscopic aspects, diagnostic staging and recurrence were considered. When there was intraoperative biopsy, its accuracy was evaluated. RESULTS: Age ranged from 27 to 79 years (mean: 53 and the follow-up from 12 to 96 months (mean: 42. The main symptoms were post-menopause bleeding (45%, abdominal pain (35% and palpable mass (25%. Most tumors were yellowish (60% and the solid aspect (40% was more common than the cystic or solid-cystic. The histological patterns were 40% solid, 15% macrofollicular and 45% combined forms. All of them with low mitotic index. Only three out of nine intraoperative frozen sections were accurately diagnosed. The clinical staging was 13 cases in Ia (65%, one case Ic and 6 IIIc. In three out of 14 hysterectomies there was simple endometrial hyperplasia with no atypia. Only the disease staging was significantly associated with recurrence (p INTRODUÇÃO E OBJETIVO: O tumor de células da granulosa tipo adulto (TCGA corresponde a menos de 5% das neoplasias ovarianas. São de baixo potencial de malignidade, podem recorrer depois de muitos anos, e o diferencial deve ser feito com outras neoplasias primárias ou metastáticas. Analisamos os aspectos clínicos e patológicos do tumor, relacionando-os à evolução. MÉTODOS: Na revisão de 10 anos dos arquivos do laboratório de Anatomia Patológica do Hospital das Clínicas da

  7. Influência de diferentes concentrações de etileno glicol nO número de células da granulosa e morfometria de folículos pré-antrais inclusos em tecido ovariano de Bos taurus indicus, Linnaeus, 1758 Influence of different concentrations of the glycol in the number of granulosa cells and morphometry of the preantral ovarian follicles of Bos taurus indicus, Linnaeus, 1758

    Directory of Open Access Journals (Sweden)

    Hélder Silva e Luna

    2010-12-01

    Full Text Available A criopreservação de folículos ovarianos pré-antrais pode ajudar na conservação de muitas espécies domésticas e selvagens. Neste trabalho, objetivou-se verificar o efeito do etileno glicol, em diferentes concentrações, na morfometria e número de células da granulosa de folículos pré-antrais inclusos em tecido ovariano bovino. O teste de toxicidade foi realizado com fragmentos ovarianos expostos ao etileno glicol em concentrações de 10, 20 ou 40%. O tecido foi analisado por técnica histológica clássica. Os folículos primordiais expostos à concentração de 40% apresentaram redução do diâmetro folicular e ovocitário quando comparados ao grupo controle (sem exposição, 10% e 20% (P0,05. Esses resultados sugerem que folículos primários são mais resistentes aos efeitos do etileno glicol quando comparados aos primordiais.The cryopreservation of the ovarian preantral follicles could help the conservation of several domestic and wild animal species. The objective of this study was to verify the effect of different concentrations of ethylene glycol on the morphometry and number of granulosa cells of the preantral ovarian follicles. A toxicity test was conducted with strips of ovarian cortex using ethylene glycol (10, 20 or 40%. Tissue analysis was done using classical histology techniques. The primordial follicles expose at a concentration of 40% showed reduction of the follicular diameter and oocyte when compared to the control (non exposing, 10 and 20% groups (P0.05. These results suggest that primary follicles are more resistant to the effect of ethylene glycol when compared to primordial ones.

  8. Modulation of Steroidogenic Pathway in Rat Granulosa Cells with Subclinical Cd Exposure and Insulin Resistance: An Impact on Female Fertility

    Directory of Open Access Journals (Sweden)

    Muskaan Belani

    2014-01-01

    Full Text Available Changes in lifestyle lead to insulin resistance (IR in females ultimately predisposing them towards infertility. In addition, cadmium (Cd, an environmental endocrine disruptor, is reported for detrimental effects on granulosa cells, thus leading to ovarian dysfunction. A combination of these factors, lifestyle and environment, seems to play a role in etiology of idiopathic infertility that accounts for 50% amongst the total infertility cases. To address this issue, we made an attempt to investigate the extent of Cd impact on insulin-resistant (IR granulosa cells. We exposed adult female Charles Foster rats to dexamethasone and confirmed IR condition by fasting insulin resistance index (FIRI. On treatment of IR rats with Cd, the preliminary studies demonstrated prolonged estrous cyclicity, decrease in serum estradiol concentrations, abnormal histology of ovary, and increased granulosa cell death. Further gene and protein expression studies of steroidogenic acute regulatory (StAR protein, 17β-hydroxysteroid dehydrogenase (17β-HSD, and cytochrome P450 aromatase (CYP19A1 were performed. Protein expression studies demonstrated significant decrease in treated groups when compared with control. Study revealed that, in spite of the molecular parameters being affected at varied level, overall ovarian physiology is maximally affected in IR and Cd coexposed group, thus mimicking the condition similar to those prevailing in infertile females.

  9. Adult Type Granulosa Cell Tumor: A Very Rare Case of Sex-Cord Tumor of the Testis with Review of the Literature

    Directory of Open Access Journals (Sweden)

    Dimosthenis Miliaras

    2013-01-01

    Full Text Available Granulosa cell tumor (GST is a sex-cord/stromal neoplasm of the gonads, more commonly arising in the ovaries, while approximately 80 cases have been reported in the testes. Out of these, 30 cases were of the adult type, while the remainder 50 cases were of the juvenile type. The latter mostly concerned infants and followed a benign course. However, the adult type testicular GCTs may be potentially malignant as it also happens in female patients with such neoplasms. We present a case of an adult type GCT located at the left testis. The patient was subjected to total orchiectomy and received no further treatment. Histology showed typical GCT histomorphology with Call-Exner bodies in some places. The immunoprofile of the tumor was CD99 (+, calretinin (+, inhibin (+, alpha smooth muscle actin (+, vimentin (+, ER (−, PR (−, keratin AE1/AE3 (−, alpha fetoprotein (−, CD117 (−, and placental alkaline phosphatase (−. Two years after surgery, the patient is alive and well with no signs of recurrence.

  10. Identification of new ovulation-related genes in humans by comparing the transcriptome of granulosa cells before and after ovulation triggering in the same controlled ovarian stimulation cycle

    DEFF Research Database (Denmark)

    Wissing, M L; Kristensen, S G; Andersen, C Y;

    2014-01-01

    with ovarian cancer, while down-regulated genes mainly represented cell cycle and proliferation. WHAT IS KNOWN ALREADY: Radical changes occur in the follicle during final follicle maturation after the ovulatory trigger: these range from ensuring an optimal milieu for the oocyte in meiotic arrest to the release...... of a mature oocyte and remodeling into a corpus luteum. A wide range of mediators of final follicle maturation has been identified in rodents, non-human primates and cows. STUDY DESIGN, SIZE, DURATION: Prospective cohort study including 24 women undergoing ovarian stimulation with the long gonadotrophin-releasing...... hormone agonist protocol during 2010-2012 at Holbæk Fertility Clinic. Nine paired samples of GC and 24 paired samples of follicular fluid (FF) were obtained before and after recombinant human chorionic gonadotrophin (rhCG) administration. PARTICIPANTS/MATERIALS, SETTING, METHODS: Nine paired (nine arrays...

  11. Extraovarian granulosa cell tumor

    Directory of Open Access Journals (Sweden)

    Paul Prabir

    2009-04-01

    Full Text Available Extraovarian granulosa cell tumor (GCT is a very uncommon tumor, assumed to arise from the ectopic gonadal tissue along the embryonal route of the genital ridge. One such rare case of extraovarian GCT was encountered in a 58-year-old female who presented with a large intraabdominal lump. Computerized tomography revealed one large retroperitoneal mass measuring 15cm x 16cm and another mesenteric mass of 8cm x 5cm size. The patient had a history of hysterectomy with bilateral salpingooophorectomy 20 years ago for uterine leiomyoma. Ultrasonography-guided aspiration smears revealed cytological features suggestive of GCT. Histopathological examination of the excised masses showed features of adult-type GCT. Because metastatic epithelial tumors, particularly from the ovaries, may show identical morphology, immunostains for inhibin and epithelial membrane antigen (EMA were performed. The tumor showed positivity for inhibin while EMA was negative thus confirming the diagnosis of GCT. As this patient had no previous history of GCT and was oophorectomized 20 years ago, the tumor was considered as extraovarian. A diagnosis of extraovarian GCT should be carried out after excluding any previous history of GCT of the ovary. Immunostains help to differentiate GCTs from other neoplasms.

  12. Changes in brain ribonuclease (BRB) messenger RNA in granulosa cells (GCs) of dominant vs subordinate ovarian follicles of cattle and the regulation of BRB gene expression in bovine GCs.

    Science.gov (United States)

    Dentis, J L; Schreiber, N B; Gilliam, J N; Schutz, L F; Spicer, L J

    2016-04-01

    Brain ribonuclease (BRB) is a member of the ribonuclease A superfamily that is constitutively expressed in a range of tissues and is the functional homolog of human ribonuclease 1. This study was designed to characterize BRB gene expression in granulosa cells (GCs) during development of bovine dominant ovarian follicles and to determine the hormonal regulation of BRB in GCs. Estrous cycles of Holstein cows (n = 18) were synchronized, and cows were ovariectomized on either day 3 to 4 or day 5 to 6 after ovulation during dominant follicle growth and selection. Ovaries were collected, follicular fluid (FFL) was aspirated, and GCs were collected for RNA isolation and quantitative polymerase chain reaction. Follicles were categorized as small (1-5 mm; pooled per ovary), medium (5-8 mm; individually collected), or large (8.1-17 mm; individually collected) based on surface diameter. Estradiol (E2) and progesterone (P4) levels were measured by radioimmunoassay (RIA) in FFL. Abundance of BRB messenger RNA (mRNA) in GCs was 8.6- to 11.8-fold greater (P P4) follicles. In the largest 4 follicles, GCs BRB mRNA abundance was negatively correlated (P mRNA abundance, and tumor necrosis factor alpha decreased (P mRNA abundance in large-follicle GCs. In experiment 3 to 6, E2, follicle-stimulating hormone, fibroblast growth factor 9, cortisol, wingless 3A, or sonic hedgehog did not affect (P > 0.10) abundance of BRB mRNA in GCs; thyroxine and luteinizing hormone increased (P mRNA abundance in small-follicle GCs. Treatment of small-follicle GCs with recombinant human RNase1 increased (P < 0.05) GCs numbers and E2 production. In conclusion, BRB is a hormonally and developmentally regulated gene in bovine GCs and may regulate E2 production during follicular growth in cattle. PMID:26773365

  13. Sonographic Quantification of Ovarian Volumes in an adult Nigeria population

    Directory of Open Access Journals (Sweden)

    Dr. Nzotta Christian

    2009-01-01

    Full Text Available This study was conducted to establish the normal values of ovarian volumes in this locality. A convenience sample of 141 apparently and gynecologically healthy and non pregnant females was studied using transabdominal sonography. The length, width and anteroposterior dimensions of both the right and left ovaries were measured. Volumes of the ovaries were determined using the prolate ellipsoid formula. The mean ovarian volumes were found to be a 9.5cm3 and 10.cm3 for the right and left ovaries respectively. A mean ovarian volume (Right and left was 9.9cm3. A mean (right and left range of 5.3cm3 to 13.9cm3 was also established. Significant correlations were noted between ovarian volumes and age (r=0.93, p<0.05 and between ovarian volumes and body weight (r=0.73, p<0.05. This study has established a nomogram for ovarian sizes in this locality which would offer a valid method of evaluating ovarian volumes in clinical practice.

  14. Sonographic Quantification of Ovarian Volumes in an adult Nigeria population

    OpenAIRE

    Dr. Nzotta Christian; Ugwu Anthony Chukwuka; Mr. Eze Joseph

    2009-01-01

    This study was conducted to establish the normal values of ovarian volumes in this locality. A convenience sample of 141 apparently and gynecologically healthy and non pregnant females was studied using transabdominal sonography. The length, width and anteroposterior dimensions of both the right and left ovaries were measured. Volumes of the ovaries were determined using the prolate ellipsoid formula. The mean ovarian volumes were found to be a 9.5cm3 and 10.cm3 for the right and left ovari...

  15. Tumeur juvénile de la granulosa de l'ovaire: à propos d'un cas

    OpenAIRE

    Azahouani, Ahmed; Balahcen, Mohamed

    2015-01-01

    Ovarian sex cord tumors are rare tumors that develop at the expense of non-germ cell ovarian. The pathogenesis of these tumors remains undetermined and several cellular and molecular alterations may be involved in the development of juvenile granulosa cell tumors. For two decades, the individualization of juvenile granulosa cell tumors has been a major advance in the treatment of these children's tumors. However, their natural history is reported in the literature and through a short series a...

  16. Paclitaxel and Carboplatin or Bleomycin Sulfate, Etoposide Phosphate, and Cisplatin in Treating Patients With Advanced or Recurrent Sex Cord-Ovarian Stromal Tumors

    Science.gov (United States)

    2016-03-16

    Ovarian Granulosa Cell Tumor; Ovarian Gynandroblastoma; Ovarian Sertoli-Leydig Cell Tumor; Ovarian Sex Cord Tumor With Annular Tubules; Ovarian Sex Cord-Stromal Tumor; Ovarian Sex Cord-Stromal Tumor of Mixed or Unclassified Cell Types; Ovarian Steroid Cell Tumor

  17. Anti-Mullerian hormone and ovarian dysfunction

    NARCIS (Netherlands)

    Broekmans, Frank J.; Visser, Jenny A.; Laven, Joop S. E.; Broer, Simone L.; Themmen, Axel P. N.; Fauser, Bart C.

    2008-01-01

    Anti-Mullerian hormone (AMH) has important roles in postnatal ovarian function. Produced by ovarian granulosa cells, AMH is involved in initial follicle development. In fact, serum AMH level correlates with ovarian follicle number. In patients with polycystic ovary syndrome (PCOS), AMH levels are el

  18. Oocyte-granulosa-theca cell interactions during preantral follicular development

    Directory of Open Access Journals (Sweden)

    Orisaka Makoto

    2009-07-01

    Full Text Available Abstract The preantral-early antral follicle transition is the penultimate stage of follicular development in terms of gonadotropin dependence and follicle destiny (growth versus atresia. Follicular growth during this period is tightly regulated by oocyte-granulosa-theca cell interactions. Formation of the theca cell layer is a key event that occurs during this transitional stage. Granulosal factor(s stimulates the recruitment of theca cells from cortical stromal cells, while oocyte-derived growth differentiation factor-9 (GDF-9 is involved in the differentiation of theca cells during this early stage of follicular development. The preantral to early antral transition is most susceptible to follicular atresia. GDF-9 promotes follicular survival and growth during transition from preantral stage to early antral stage by suppressing granulosa cell apoptosis and follicular atresia. GDF-9 also enhances preantral follicle growth by up-regulating theca cell androgen production. Thecal factor(s promotes granulosa cell proliferation and suppress granulosa cell apoptosis. Understanding the intraovarian mechanisms in the regulation of follicular growth and atresia during this stage may be of clinical significance in the selection of the best quality germ cells for assisted reproduction. In addition, since certain ovarian dysfunctions, such as polycystic ovarian syndrome and gonadotropin poor-responsiveness, are consequences of dysregulated follicle growth at this transitional stage, understanding the molecular and cellular mechanisms in the control of follicular development during the preantral-early antral transition may provide important insight into the pathophysiology and rational treatment of these conditions.

  19. Animal models of ovarian cancer

    OpenAIRE

    Shaw Tanya J; Vanderhyden Barbara C; Ethier Jean-François

    2003-01-01

    Abstract Ovarian cancer is the most lethal of all of the gynecological cancers and can arise from any cell type of the ovary, including germ cells, granulosa or stromal cells. However, the majority of ovarian cancers arise from the surface epithelium, a single layer of cells that covers the surface of the ovary. The lack of a reliable and specific method for the early detection of epithelial ovarian cancer results in diagnosis occurring most commonly at late clinical stages, when treatment is...

  20. Ignored adult primary hypothyroidism presenting chiefly with persistent ovarian cysts: a need for increased awareness

    Directory of Open Access Journals (Sweden)

    Fang Suhua

    2011-08-01

    Full Text Available Abstract Background Ovarian cysts are a common cause for gynecological surgery. However, some cysts are a direct result of endocrine disorders and do not require surgery. This report describes an unusual case in which persistent ovarian cysts are associated with primary hypothyroidism in a young woman. The data were collected by history-taking, physical examination, laboratory tests, ultrasound, magnetic resonance imaging and a histo-pathological study. In addition, the exons of the gene encoding the human follicle-stimulating hormone receptor were sequenced. Discussion The patient had markedly elevated levels of thyroid-stimulating hormone and follicle-stimulating hormone and an enlarged pituitary gland. After treatment with thyroid hormone replacement, regression of the enlarged pituitary and the ovarian cysts was observed. The possible mechanisms of the pathophysiology are discussed below. Summary It is necessary to consider hypothyroidism and other endocrine disorders in the differential diagnosis of adult patients with ovarian multiple cyst formation in order to prevent inadvertent ovarian surgery.

  1. Effect of vitamin D3 on production of progesterone in porcine granulosa cells by regulation of steroidogenic enzymes.

    Science.gov (United States)

    Hong, So-Hye; Lee, Jae-Eon; Kim, Hong Sung; Jung, Young-Jin; Hwang, DaeYoun; Lee, Jae Ho; Yang, Seung Yun; Kim, Seung-Chul; Cho, Seong-Keun; An, Beum-Soo

    2016-05-01

    1,25-dihydroxyvitamin D3 (VD3), an active form of Vitamin D, is photosynthesized in the skin of vertebrates in response to solar ultraviolet B radiation (UV-B). VD3 deficiency can cause health problems such as immune disease, metabolic disease, and bone disorders. It has also been demonstrated that VD3 is involved in reproductive functions. Female sex hormones such as estrogen and progesterone are biosynthesized mainly in ovarian granulosa cells as the ovarian follicle develops. The functions of sex hormones include regulation of the estrus cycle and puberty as well as maintenance of pregnancy in females. In this study, we isolated granulosa cells from porcine ovaries and cultured them for experiments. To examine the effects of VD3 on ovarian granulosa cells, the mRNA and protein levels of genes were analyzed by Real-time PCR and Western blotting assay. Production of progesterone from granulosa cells was also measured by ELISA assay. As a result, transcriptional and translational regulation of progesterone biosynthesis-related genes in granulosa cells was significantly altered by VD3. Furthermore, progesterone concentrations in porcine granulosa cell-cultured media decreased in response to VD3. These results show that VD3 was a strong regulator of sex steroid hormone production in porcine granulosa cells, suggesting that vitamin D deficiency may result in inappropriate sexual development of industrial animals and eventually economic loss. PMID:27533930

  2. The fungicide mancozeb induces toxic effects on mammalian granulosa cells

    Energy Technology Data Exchange (ETDEWEB)

    Paro, Rita [Department of Health Sciences, University of L' Aquila, Via Vetoio, L' Aquila (Italy); Tiboni, Gian Mario [Department of Medicine and Aging, Section of Reproductive Sciences, University “G. D' Annunzio”, Chieti-Pescara (Italy); Buccione, Roberto [Tumor Cell Invasion Laboratory, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti (Italy); Rossi, Gianna; Cellini, Valerio [Department of Health Sciences, University of L' Aquila, Via Vetoio, L' Aquila (Italy); Canipari, Rita [Department of Anatomy, Histology, Forensic Medicine and Orthopedics, Section of Histology and Embryology, School of Pharmacy and Medicine, “Sapienza” University of Rome, Rome (Italy); Cecconi, Sandra, E-mail: sandra.cecconi@cc.univaq.it [Department of Health Sciences, University of L' Aquila, Via Vetoio, L' Aquila (Italy)

    2012-04-15

    The ethylene-bis-dithiocarbamate mancozeb is a widely used fungicide with low reported toxicity in mammals. In mice, mancozeb induces embryo apoptosis, affects oocyte meiotic spindle morphology and impairs fertilization rate even when used at very low concentrations. We evaluated the toxic effects of mancozeb on the mouse and human ovarian somatic granulosa cells. We examined parameters such as cell morphology, induction of apoptosis, and p53 expression levels. Mouse granulosa cells exposed to mancozeb underwent a time- and dose-dependent modification of their morphology, and acquired the ability to migrate but not to proliferate. The expression level of p53, in terms of mRNA and protein content, decreased significantly in comparison with unexposed cells, but no change in apoptosis was recorded. Toxic effects could be attributed, at least in part, to the presence of ethylenthiourea (ETU), the main mancozeb catabolite, which was found in culture medium. Human granulosa cells also showed dose-dependent morphological changes and reduced p53 expression levels after exposure to mancozeb. Altogether, these results indicate that mancozeb affects the somatic cells of the mammalian ovarian follicles by inducing a premalignant-like status, and that such damage occurs to the same extent in both mouse and human GC. These results further substantiate the concept that mancozeb should be regarded as a reproductive toxicant. Highlights: ► The fungicide mancozeb affects oocyte spindle morphology and fertilization rate. ► We investigated the toxic effects of mancozeb on mouse and human granulosa cells. ► Granulosa cells modify their morphology and expression level of p53. ► Mancozeb induces a premalignant-like status in exposed cells.

  3. 黄芪多糖对体外培养多囊卵巢综合征患者卵巢颗粒细胞雄激素分泌异常的影响%The effect of astragalus polysaccharides on androgen excess within ovarian granulosa cells of PCOS patients in vitro

    Institute of Scientific and Technical Information of China (English)

    张雅娟; 桑敏; 张洪秀; 李力男; 吕荟明; 安媛

    2011-01-01

    目的 探索多囊卵巢综合征(PCOS)患者卵巢颗粒细胞雄激素分泌的变化及黄芪多糖对其雄激素分泌变化的影响.方法 收集行IVF/ICSI-ET 17例PCOS患者的卵巢颗粒细胞进行体外培养,用浓度为50、100、200、500、1000 μg/ml的黄芪多糖分别作用于体外培养的PCOS患者卵巢颗粒细胞,检测其培养液中雌激素(E2)、孕激素(P)、雄激素(T)水平的变化.结果 PCOS患者卵巢颗粒细胞分泌T水平[(0.4716±0.03)nmol/L]明显高于对照组[(0.23 ±0.0162) nmol/L,P<0.05],两组E2、P水平比较差异均无统计学意义(P>0.05).给予不同浓度黄芪多糖处理后,PCOS组患者颗粒细胞培养液中T水平明显降低(P<0.01).黄芪多糖浓度分别为1000、500、200、100及50μg/ml的T水平与0μg/ml相比,其差异均有统计学意义(P<0.01).结论 黄芪多糖能抑制PCOS患者卵巢颗粒细胞体外培养中的睾酮分泌,降低睾酮分泌水平,可成为治疗PCOS患者的新途径.%Objective To study androgen excess within ovarian granulosa cells of PCOS patients in vitro,and the partial improvement by using astragalus polysaccharides.Methods Ovarian granulosa cells from the PCOS patients during IVF / ICSI - ET were isolated and cultured in vitro,then it was treated by different concentrations of astragalus polysaccharides.The levels of estradiol,progesterone and testosterone were determined.Results Androgen secretion within ovarian granulosa cells from PCOS patients was significantly increased [ ( 0.4716 ± 0.03 ) nmol/L,( 0.23 ± 0.0162 ) nmol/L,P < 0.05 ].The levels of estradiol and progesterone were not significantly different( P > 0.05 ).Different concentrations of astragalus polysaccharides may result from the alleviation of androgen secretion which was commonly found in PCOS treatment (concentration was 1000 μg/ml,100 μg/ml,50 μg/ml,P < 0.01 ;concentration was 500 μg/ml,P =0.002 ; concentration was 200 μg/ml,P =0.003).Conclusions Astragalus

  4. Fetal and neonatal exposure to the endocrine disruptor methoxychlor causes epigenetic alterations in adult ovarian genes.

    Science.gov (United States)

    Zama, Aparna Mahakali; Uzumcu, Mehmet

    2009-10-01

    Exposure to endocrine-disrupting chemicals during development could alter the epigenetic programming of the genome and result in adult-onset disease. Methoxychlor (MXC) and its metabolites possess estrogenic, antiestrogenic, and antiandrogenic activities. Previous studies showed that fetal/neonatal exposure to MXC caused adult ovarian dysfunction due to altered expression of key ovarian genes including estrogen receptor (ER)-beta, which was down-regulated, whereas ERalpha was unaffected. The objective of the current study was to evaluate changes in global and gene-specific methylation patterns in adult ovaries associated with the observed defects. Rats were exposed to MXC (20 microg/kgxd or 100 mg/kg.d) between embryonic d 19 and postnatal d 7. We performed DNA methylation analysis of the known promoters of ERalpha and ERbeta genes in postnatal d 50-60 ovaries using bisulfite sequencing and methylation-specific PCRs. Developmental exposure to MXC led to significant hypermethylation in the ERbeta promoter regions (P < 0.05), whereas the ERalpha promoter was unaffected. We assessed global DNA methylation changes using methylation-sensitive arbitrarily primed PCR and identified 10 genes that were hypermethylated in ovaries from exposed rats. To determine whether the MXC-induced methylation changes were associated with increased DNA methyltransferase (DNMT) levels, we measured the expression levels of Dnmt3a, Dnmt3b, and Dnmt3l using semiquantitative RT-PCR. Whereas Dnmt3a and Dnmt3l were unchanged, Dnmt3b expression was stimulated in ovaries of the 100 mg/kg MXC group (P < 0.05), suggesting that increased DNMT3B may cause DNA hypermethylation in the ovary. Overall, these data suggest that transient exposure to MXC during fetal and neonatal development affects adult ovarian function via altered methylation patterns.

  5. Extracellular matrix in ovarian follicles.

    Science.gov (United States)

    Rodgers, R J; Irving-Rodgers, H F; van Wezel, I L

    2000-05-25

    A lot is known about the control of the development of ovarian follicles by growth factors and hormones, but less is known about the roles of extracellular matrix in the control of follicular growth and development. In this review we focus on the specialized extracellular matrix of the basal laminas that are present in ovarian follicles. These include the follicular basal lamina itself, the Call-Exner bodies of the membrana granulosa, the subendothelial and arteriole smooth muscle basal laminas in the theca, and the basal lamina-like material of the thecal matrix. We discuss the evidence that during follicle development the follicular basal lamina changes in composition, that many of its components are produced by the granulosa cells, and that the follicular basal laminas of different follicles have different ultrastructural appearances, linked to the shape of the aligning granulosa cells. All these studies suggest that the follicular basal lamina is extremely dynamic during follicular development. PMID:10963877

  6. Genotoxicity of Superparamagnetic Iron Oxide Nanoparticles in Granulosa Cells

    Directory of Open Access Journals (Sweden)

    Marina Pöttler

    2015-11-01

    Full Text Available Nanoparticles that are aimed at targeting cancer cells, but sparing healthy tissue provide an attractive platform of implementation for hyperthermia or as carriers of chemotherapeutics. According to the literature, diverse effects of nanoparticles relating to mammalian reproductive tissue are described. To address the impact of nanoparticles on cyto- and genotoxicity concerning the reproductive system, we examined the effect of superparamagnetic iron oxide nanoparticles (SPIONs on granulosa cells, which are very important for ovarian function and female fertility. Human granulosa cells (HLG-5 were treated with SPIONs, either coated with lauric acid (SEONLA only, or additionally with a protein corona of bovine serum albumin (BSA; SEONLA-BSA, or with dextran (SEONDEX. Both micronuclei testing and the detection of γH2A.X revealed no genotoxic effects of SEONLA-BSA, SEONDEX or SEONLA. Thus, it was demonstrated that different coatings of SPIONs improve biocompatibility, especially in terms of genotoxicity towards cells of the reproductive system.

  7. Role of leptin receptors in granulosa cells during ovulation.

    Science.gov (United States)

    Dupuis, Lisa; Schuermann, Yasmin; Cohen, Tamara; Siddappa, Dayananda; Kalaiselvanraja, Anitha; Pansera, Melissa; Bordignon, Vilceu; Duggavathi, Raj

    2014-02-01

    Leptin is an important hormone influencing reproductive function. However, the mechanisms underpinning the role of leptin in the regulation of reproduction remain to be completely deciphered. In this study, our objective is to understand the mechanisms regulating the expression of leptin receptor (Lepr) and its role in ovarian granulosa cells during ovulation. First, granulosa cells were collected from superovulated mice to profile mRNA expression of Lepr isoforms (LeprA and LeprB) throughout follicular development. Expression of LeprA and LeprB was dramatically induced in the granulosa cells of ovulating follicles at 4 h after human chorionic gonadotropin (hCG) treatment. Relative abundance of both mRNA and protein of CCAAT/enhancer-binding protein β (Cebpβ) increased in granulosa cells from 1 to 7 h post-hCG. Furthermore, chromatin immunoprecipitation assay confirmed the recruitment of Cebpβ to Lepr promoter. Thus, hCG-induced transcription of Lepr appears to be regulated by Cebpβ, which led us to hypothesise that Lepr may play a role during ovulation. To test this hypothesis, we used a recently developed pegylated superactive mouse leptin antagonist (PEG-SMLA) to inhibit Lepr signalling during ovulation. I.p. administration of PEG-SMLA (10 μg/g) to superovulated mice reduced ovulation rate by 65% compared with control treatment. Although the maturation stage of the ovulated oocytes remained unaltered, ovulation genes Ptgs2 and Has2 were downregulated in PEG-SMLA-treated mice compared with control mice. These results demonstrate that Lepr is dramatically induced in the granulosa cells of ovulating follicles and this induction of Lepr expression requires the transcription factor Cebpβ. Lepr plays a critical role in the process of ovulation by regulating, at least in part, the expression of the important genes involved in the preovulatory maturation of follicles.

  8. Effect of follicle stimulating hormone on the secretion of anti-mullerian hormone in the granulosa cells in patients with polycystic ovarian syndrome%卵泡刺激素对多囊卵巢综合征患者卵巢颗粒细胞分泌抗苗勒管激素的影响

    Institute of Scientific and Technical Information of China (English)

    李轶; 梁晓燕

    2012-01-01

    目的 研究卵泡刺激素(FSH)对多囊卵巢综合征(PCOS)患者卵巢颗粒细胞分泌抗苗勒管激素(AMH)的影响.方法 选择2008年8月至2009年12月于中山大学附属第六医院生殖中心就诊的33例PCOS患者,从其直径为8~10 mm的窦卵泡中分离颗粒细胞,并分为以下3组进行培养:未经FSH刺激的颗粒细胞(未刺激组,n=12);外源性FSH刺激的颗粒细胞(体外刺激组,n=12),此组颗粒细胞来源同未刺激组;对患者行FSH促排卵治疗,采集FSH体内刺激的颗粒细胞(体内刺激组,n=21).分别采用ELISA法和实时荧光定量PCR技术检测培养液中颗粒细胞分泌的AMH水平,及AHM mRNA表达水平;构建AMH荧光报告载体,检测卵巢颗粒细胞中AMH启动子的活性.结果 培养液中颗粒细胞分泌的AMH水平,未刺激组为(11.4±4.0)μg/L,体外刺激组为(7.9±1.1)μg/L,体内刺激组为(5.6±1.7)μg/L,体内、体外刺激组分别与未刺激组比较,差异均有统计学意义(P均<0.05).AMH mRNA表达水平未刺激组为2.5±1.2,体外刺激组为1.5±0.5,体内刺激组为1.1±0.7,未刺激组高于体内、外刺激组,分别比较,差异均有统计学意义(P均<0.05).未刺激组颗粒细胞中AMH启动子的活性为11.5±2.3,体外刺激组为8.7±2.4,体内刺激组为6.8±2.4,未刺激组高于体内、外刺激组,分别比较,差异均有统计学意义(P均<0.05).结论 FSH可能通过抑制PCOS患者卵巢颗粒细胞中AMH的启动子活性及其mRNA表达,抑制AHM的过度分泌,促进卵泡的生长发育.%Objective To study the effect of follicle stimulating hormone(FSH)on the secretion of anti-mullerian hormone(AMH)in granulosa cells in patients with polycystic ovarian syndrome(PCOS).Methods From Aug.2008 to Dec.2009,33 patients with PCOS in Reproductive Medicine Research Center,Sixth Affiliated Hospital of Sun Yat-sen University were collected from 8-10 mm antral follicles and classified into the following three groups: FSH

  9. Proprotein convertase furin regulates apoptosis and proliferation of granulosa cells in the rat ovary.

    Directory of Open Access Journals (Sweden)

    Xiaokui Yang

    Full Text Available Folliculogenesis is tightly controlled by a series of hormones, growth factors and cytokines, many of which are secreted as proproteins and require processing by proteases before becoming functional. Furin is a member of the subtilisin-like proteases that activate large numbers of proprotein substrates and is ubiquitously expressed and implicated in many physiological and pathological processes. However, the precise role of furin during folliculogenesis has not been thoroughly investigated. The goal of the present work is to identify the role of furin in the development of granulosa cells during folliculogenesis, using immunohistochemistry, RT-PCR, Western blot and functional studies in primary cultured rat granulosa cells. Our results demonstrate that furin is highly expressed in granulosa cells and oocytes of the ovary with very limited expression in other ovarian cells such as the epithelial, stromal or theca cells. Furin siRNA significantly increases apoptosis of the granulosa cells from large antral/preovulatory follicles, in part via downregulation of the anti-apoptotic proteins, XIAP and p-AKT. On the contrary, furin siRNA markedly decreases proliferation of granulosa cells based on the downregulation of proliferation cell nuclear antigen (PCNA. Taken together, these data suggest that furin may play an important role in regulating apoptosis and proliferation of granulosa cells.

  10. Human granulosa-luteal cells initiate an innate immune response to pathogen-associated molecules.

    Science.gov (United States)

    Ibrahim, Laila A; Kramer, Joseph M; Williams, R Stan; Bromfield, John J

    2016-10-01

    The microenvironment of the ovarian follicle is key to the developmental success of the oocyte. Minor changes within the follicular microenvironment can significantly disrupt oocyte development, compromising the formation of competent embryos and reducing fertility. Previously described as a sterile environment, the ovarian follicle of women has been shown to contain colonizing bacterial strains, whereas in domestic species, pathogen-associated molecules are concentrated in the follicular fluid of animals with uterine infection. The aim of this study is to determine whether human granulosa-luteal cells mount an innate immune response to pathogen-associated molecules, potentially disrupting the microenvironment of the ovarian follicle. Human granulosa-luteal cells were collected from patients undergoing assisted reproduction. Cells were cultured in the presence of pathogen-associated molecules (LPS, FSL-1 and Pam3CSK4) for 24h. Supernatants and total RNA were collected for assessment by PCR and ELISA. Granulosa-luteal cells were shown to express the molecular machinery required to respond to a range of pathogen-associated molecules. Expression of TLR4 varied up to 15-fold between individual patients. Granulosa-luteal cells increased the expression of the inflammatory mediators IL1B, IL6 and CXCL8 in the presence of the TLR4 agonist E. coli LPS. Similarly, the TLR2/6 ligand, FSL-1, increased the expression of IL6 and CXCL8. Although no detectable changes in CYP19A1 or STAR expression were observed in granulosa-luteal cells following challenge, a significant reduction in progesterone secretion was measured after treatment with FSL-1. These findings demonstrate the ability of human granulosa-luteal cells to respond to pathogen-associated molecules and generate an innate immune response. PMID:27512120

  11. Developmental methoxychlor exposure affects multiple reproductive parameters and ovarian folliculogenesis and gene expression in adult rats.

    Science.gov (United States)

    Armenti, AnnMarie E; Zama, Aparna Mahakali; Passantino, Lisa; Uzumcu, Mehmet

    2008-12-01

    Methoxychlor (MXC) is an organochlorine pesticide with estrogenic, anti-estrogenic, and anti-androgenic properties. To investigate whether transient developmental exposure to MXC could cause adult ovarian dysfunction, we exposed Fischer rats to 20 microg/kg/day (low dose; environmentally relevant dose) or 100 mg/kg/day (high dose) MXC between 19 days post coitum and postnatal day 7. Multiple reproductive parameters, serum hormone levels, and ovarian morphology and molecular markers were examined from prepubertal through adult stages. High dose MXC accelerated pubertal onset and first estrus, reduced litter size, and increased irregular cyclicity (P<0.05). MXC reduced superovulatory response to exogenous gonadotropins in prepubertal females (P<0.05). Rats exposed to high dose MXC had increasing irregular estrous cyclicity beginning at 4 months of age, with all animals showing abnormal cycles by 6 months. High dose MXC reduced serum progesterone, but increased luteinizing hormone (LH). Follicular composition analysis revealed an increase in the percentage of preantral and early antral follicles and a reduction in the percentage of corpora lutea in high dose MXC-treated ovaries (P<0.05). Immunohistochemical staining and quantification of the staining intensity showed that estrogen receptor beta was reduced by high dose MXC while anti-Mullerian hormone was upregulated by both low- and high dose MXC in preantral and early antral follicles (P<0.05). High dose MXC significantly reduced LH receptor expression in large antral follicles (P<0.01), and down-regulated cytochrome P450 side-chain cleavage. These results demonstrated that developmental MXC exposure results in reduced ovulation and fertility and premature aging, possibly by altering ovarian gene expression and folliculogenesis.

  12. A study of glucose metabolism in the ovarian granulosa cells of obese patients with PCOS%肥胖型多囊卵巢综合征患者卵巢颗粒细胞中糖代谢的研究

    Institute of Scientific and Technical Information of China (English)

    庄明慧; 吕梁; 陆晓媛; 黄晓洁; 宋雪梅

    2015-01-01

    目的:研究酪氨酸216位点磷酸化糖原合成酶激酶-3β〔p -GSK -3β(Try216)〕在肥胖多囊卵巢综合征(PCOS)患者卵巢颗粒细胞中的表达。方法选择因 PCOS、不孕行体外受精/单精子卵胞浆内注射-胚胎移植(IVF/ICSI -ET)取卵的患者10例,其中 PCOS 肥胖组〔体质指数(BMI)≥28.0 kg/m2〕5例,PCOS 非肥胖组(18.5 kg/m 2<BMI≤23.9 kg/m 2)5例;另外选择因输卵管梗阻或男方因素行 IVF/ICSI -ET 取卵者5例作为非PCOS 对照组(18.5 kg/m 2<BMI≤23.9 kg/m 2)。取卵后收集颗粒细胞进行培养,葡萄糖氧化酶(GOD)法检测第48 h 细胞培养液葡糖糖含量,免疫印迹法检测 p -GSK -3β(Try216)表达。结果非 PCOS 对照组、PCOS 非肥胖组、PCOS 肥胖组中葡萄糖含量依次增高(P <0.05),p -GSK -3β(Try216)表达量依次增加(P <0.05),差异均有统计学意义。结论PCOS 患者卵巢颗粒细胞中糖代谢异常,肥胖加重 PCOS 患者糖代谢紊乱。 p -GSK -3β(Try216)在肥胖 PCOS 患者糖代谢紊乱中发挥重要作用。%Objective To investigate the level of p -GSK -3β(Try216) in the ovarian granulosa cells of obese pa-tients with polycystic ovarian syndrome (PCOS).Methods A total of ten patients were enrolled into the current study who underwent in vitro fertilization/intracytoplasmic sperm injection and embyro transfer (IVF/ICSI -ET) due to infertil-ity caused by PCOS.These patients were divided into two groups according to their conditions: an obese PCOS group (BMI≥28 kg/m 2 , n =5) and a non -obese PCOS group (18.5 kg/m 2 Granulosa cells were collected from patients during IVF/ICSI -ET

  13. MUTATIONAL SCREEN AT THE OEYTS-JEGHERS (LKB1) LOCUS IN SPORDIC COLON AND OVARIAN TUMORS

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To screen LKB1 mutation in sporadic colon and ovarian tumors. Methods: Using PCR-SSCP analysis, 72 colon cancer, 45 ovarian cancer, 14 granulosa cell tumor were screened for LKB1 mutation. Results: no mutation was in sporadic colon and ovarian adenocarcinomas. Two mutations were detected in one of the granulosa cell tumors: a mis-sense mutation affecting the putative start codon (ATG?ACG, MIT); and a silent change in erxon 7 (CTT?CTA, leucine). Conclusion: LKB1 mutations in sporadic colon and ovarian cancers are rare event and LKB1 is not the target gene lost on chromosome 19p13.3 in ovarian cancers.

  14. Trenbolone acetate metabolites promote ovarian growth and development in adult Japanese medaka (Oryzias latipes).

    Science.gov (United States)

    Forsgren, Kristy L; Qu, Shen; Lavado, Ramon; Cwiertny, David; Schlenk, Daniel

    2014-06-01

    Trenbolone acetate, a synthetic androgen, has been used as a growth promoter in beef cattle in the US since 1987. While several teleost studies have investigated the masculinization effects of the metabolite 17β-trenbolone, few have focused on the reproductive impacts of all three trenbolone acetate (TBA) metabolites including trendione. Adult female medaka (Oryzias latipes) were exposed to TBA metabolites (10, 100, and 1000ng/L) for 14days (n=3). Histological examination revealed that TBA metabolites (1000ng/L) significantly reduced the percentage of primary ovarian follicles and increased the percentage of vitellogenic follicles compared to control fish. 17α-Trenbolone significantly increased whereas trendione reduced whole body levels of estradiol-17β. Testosterone was significantly reduced by trendione treatment and only the highest dose of 17β-trenbolone and lowest dose of trendione altered 11-ketotestosterone. Additionally, TBA metabolites may be further broken down and/or metabolized or converted by the animal influencing both sex steroid levels and ovarian development. PMID:24780119

  15. Premature Thelarche and Precocious Puberty in a Three-Year-Old Girl with Granulosa Cell Tumor

    Directory of Open Access Journals (Sweden)

    Zahra Ghanbari

    2013-07-01

    Full Text Available Granulosa cell tumors (GCTs are tumors that arise from granulosa cells, occurring in women 50 to 55 years of age but may occur at any age whereas Juvenile granulosa cell tumors usually occur in children and adolescents. A three years old girl with breast development but without any significant past medical history was referred to the Pediatric Clinic in Children hospital(University of Medical Sciences, Tabriz, Iran in July 2011.We have reported this patient with premature thelarche and isosexual precocity in this paper. Pelvic ultrasonography showed a hypoechoic solid mass and abdominopelvic MRI showed left adnexal mass with cystic components. Microscopic features of the resected mass were characteristic of juvenile GCT. Although in most of girls with precocious puberty the etiology is idiopathic, some important causes, such as ovarian tumors must be considered because most common presenting manifestation of GCT in children is precocious puberty.

  16. Mutant Forkhead L2 (FOXL2) proteins associated with premature ovarian failure (POF) dimerize with wild-type FOXL2, leading to altered regulation of genes associated with granulosa cell differentiation.

    Science.gov (United States)

    Kuo, Fang-Ting; Bentsi-Barnes, Ikuko K; Barlow, Gillian M; Pisarska, Margareta D

    2011-10-01

    Premature ovarian failure in the autosomal dominant disorder blepharophimosis-ptosis-epicanthus inversus is due to mutations in the gene encoding Forkhead L2 (FOXL2), producing putative truncated proteins. We previously demonstrated that FOXL2 is a transcriptional repressor of the steroidogenic acute regulatory (StAR), P450SCC (CYP11A), P450aromatase (CYP19), and cyclin D2 (CCND2) genes, markers of ovarian follicle proliferation and differentiation. Furthermore, we found that mutations of FOXL2 may regulate wild-type FOXL2, leading to loss of transcriptional repression of CYP19, similar to StAR. However, the regulatory mechanisms underlying these premature ovarian failure-associated mutations remain largely unknown. Therefore, we examined the effects of a FOXL2 mutant protein on the transcriptional repression of the CYP19 promoter by the full-length protein. We found that mutant FOXL2 exerts a dominant-negative effect on the repression of CYP19 by wild-type FOXL2. Both wild-type and mutant FOXL2 and can form homo- and heterodimers. We identified a minimal -57-bp human CYP19 promoter containing two potential FOXL2-binding regions and found that both wild-type and mutant FOXL2 can bind to either of these regions. Mutational analysis revealed that either site is sufficient for transcriptional repression by wild-type FOXL2, and the dominant-negative effect of mutant FOXL2, but these are eliminated when both sites are mutated. These findings confirm that mutant FOXL2 exerts a dominant-negative effect on wild-type FOXL2's activity as a transcriptional repressor of key genes in ovarian follicle differentiation and suggest that this is likely due to heterodimer formation and possibly also competition for DNA binding.

  17. The GnRH analogue triptorelin confers ovarian radio-protection to adult female rats

    International Nuclear Information System (INIS)

    There is a controversy regarding the effects of the analogues of the gonadotrophin-releasing hormone (GnRH) in radiotherapy. This has led us to study the possible radio-protection of the ovarian function of a GnRH agonist analogue (GnRHa), triptorelin, in adult, female rats (Rattus norvegicus sp.). The effects of the X-irradiation on the oocytes of ovarian primordial follicles, with and without GnRHa treatment, were compared, directly in the female rats (F0) with reproductive parameters, and in the somatic cells of the resulting foetuses (F1) with cytogenetical parameters. In order to do this, the ovaries and uteri from 82 females were extracted for the reproductive analysis and 236 foetuses were obtained for cytogenetical analysis. The cytogenetical study was based on the data from 22,151 metaphases analysed. The cytogenetical parameters analysed to assess the existence of chromosomal instability were the number of aberrant metaphases (2234) and the number (2854) and type of structural chromosomal aberrations, including gaps and breaks. Concerning the reproductive analysis of the ovaries and the uteri, the parameters analysed were the number of corpora lutea, implantations, implantation losses and foetuses. Triptorelin confers radio-protection of the ovaries in front of chromosomal instability, which is different, with respect to the single and fractioned dose. The cytogenetical analysis shows a general decrease in most of the parameters of the triptorelin-treated groups, with respect to their controls, and some of these differences were considered to be statistically significant. The reproductive analysis indicates that there is also radio-protection by the agonist, although minor to the cytogenetical one. Only some of the analysed parameters show a statistically significant decrease in the triptorelin-treated groups.

  18. The GnRH analogue triptorelin confers ovarian radio-protection to adult female rats

    Energy Technology Data Exchange (ETDEWEB)

    Camats, N. [Institut de Biotecnologia i de Biomedicina (I.B.B.), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Garcia, F. [Institut de Biotecnologia i de Biomedicina (I.B.B.), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Parrilla, J.J. [Servicio de Ginecologia y Obstetricia, Hospital Universitario Virgen de la Arrixaca, 30120 El Palmar, Murcia (Spain); Calaf, J. [Servei de Ginecologia i Obstetricia, Hospital Universitari de la Santa Creu i Sant Pau, 08025 Barcelona (Spain); Martin-Mateo, M. [Departament de Pediatria, d' Obstetricia i Ginecologia i de Medicina Preventiva, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Caldes, M. Garcia, E-mail: Montserrat.Garcia.Caldes@uab.es [Institut de Biotecnologia i de Biomedicina (I.B.B.), Universitat Autonoma de Barcelona, 08193 Barcelona (Spain); Departament de Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autonoma de Barcelona, 08193 Barcelona (Spain)

    2009-10-02

    There is a controversy regarding the effects of the analogues of the gonadotrophin-releasing hormone (GnRH) in radiotherapy. This has led us to study the possible radio-protection of the ovarian function of a GnRH agonist analogue (GnRHa), triptorelin, in adult, female rats (Rattus norvegicus sp.). The effects of the X-irradiation on the oocytes of ovarian primordial follicles, with and without GnRHa treatment, were compared, directly in the female rats (F{sub 0}) with reproductive parameters, and in the somatic cells of the resulting foetuses (F{sub 1}) with cytogenetical parameters. In order to do this, the ovaries and uteri from 82 females were extracted for the reproductive analysis and 236 foetuses were obtained for cytogenetical analysis. The cytogenetical study was based on the data from 22,151 metaphases analysed. The cytogenetical parameters analysed to assess the existence of chromosomal instability were the number of aberrant metaphases (2234) and the number (2854) and type of structural chromosomal aberrations, including gaps and breaks. Concerning the reproductive analysis of the ovaries and the uteri, the parameters analysed were the number of corpora lutea, implantations, implantation losses and foetuses. Triptorelin confers radio-protection of the ovaries in front of chromosomal instability, which is different, with respect to the single and fractioned dose. The cytogenetical analysis shows a general decrease in most of the parameters of the triptorelin-treated groups, with respect to their controls, and some of these differences were considered to be statistically significant. The reproductive analysis indicates that there is also radio-protection by the agonist, although minor to the cytogenetical one. Only some of the analysed parameters show a statistically significant decrease in the triptorelin-treated groups.

  19. Expression of Wilms' tumor protein WT-1 ,AMH,ER and PR in ovarian granulosa cell tumor%卵巢颗粒细胞瘤中WT-1蛋白、AMH、ER和PR的表达及意义

    Institute of Scientific and Technical Information of China (English)

    张盈盈; 姚汉武

    2008-01-01

    目的 探讨WT-1蛋白在卵巢颗粒细胞瘤(granulosa cell tumor,GCT)发生发展中的作用,研究它和抗苗勒管激素(anti-mullerian hormone,AMH)、雌激素受体(ER)和孕激素受体(PR)在卵巢GCT中的表达及意义. 方法 用免疫组化方法 研究WT-1蛋白、AMH、ER和PR分别在37例卵巢GCT和10例正常卵巢组织中的表达情况. 结果 WT-1蛋白、AMH、ER在卵巢GCT中的表达都明显高于它们在正常组织中的表达(P<0.05),且随组织分化程度与临床分期提高而降低,而PR的表达在正常组、不同分化组与不同临床分期组之间差异无统计学意义.WT-1蛋白和AMH的表达呈正相关关系,ER和PR的表达亦呈正相关关系. 结论 WT-1蛋白与卵巢GCT的发生发展无直接关系.它和AMH、ER可以作为卵巢GCT的辅助诊断指标,测定它们的表达可为诊断及判定预后提供理论依据.

  20. Low birth weight may increase body fat mass in adult women with polycystic ovarian syndrome

    Science.gov (United States)

    Minooee, Sonia; Ramezani Tehrani, Fahimeh; Mirmiran, Parvin; Azizi, Fereidoun

    2016-01-01

    Background: Women engaged with polycystic ovarian syndrome (PCOS), as the commonest endocrine disorder, are known to have a specific type of adiposity. Birth weight is among different contributors reported to be responsible for this diversity. Objective: We aimed to compare the relation between birth weight and body fat mass (BFM)/ body lean mass (BLM) in PCOS and their age and body mass index (BMI) matched normal controls. Materials and Methods: In this case-control study, a total number of 70 reproductive aged women, diagnosed with PCOS and 70 age- BMI matched healthy women without hirsutism and/or ovulatory dysfunction were recruited., control group had no polycystic ovaries in ultrasonographic scans. A detailed history of birth weight was taken and was divided into the following categories: PCOS than in controls (19.3% (27) vs. 15.7% (22)). Also body fat and lean mass (BFM, BLM) have increased in adult women with PCOS who were born underweight compared to their normal (19.8±9.05 vs. 12.9±4.5, p=0.001 and 48.9±6.9 vs. 43.2±5.8, p=0.004 respectively). Conclusion: Fetal birth weight influences on the adulthood obesity, BFM and BLM. This impact is different among women with and without PCOS. PMID:27326419

  1. Biochanin A affects steroidogenesis and estrogen receptor-β expression in porcine granulosa cells.

    Science.gov (United States)

    Nynca, Anna; Swigonska, Sylwia; Piasecka, Joanna; Kolomycka, Agnieszka; Kaminska, Barbara; Radziewicz-Pigiel, Marta; Gut-Nagel, Marta; Ciereszko, Renata E

    2013-10-15

    Biochanin A, similar to other isoflavones, is present in soy and soy-based food, but predominantly in red clover. Red clover extract and biochanin A were reported to affect reproductive processes as well as to demonstrate menopause relief and anticancerogenic properties. Because porcine granulosa cells provide a suitable in vitro model for studying the intracellular mechanism of phytoestrogen action in the ovary, the objective of the study was to evaluate the in vitro effects of biochanin A on the following: (1) progesterone (P4) and estradiol (E2) secretion by granulosa cells, (2) viability of the granulosa cells, and (3) mRNA and protein expression of estrogen receptors α (ERα) and β (ERβ) in the granulosa cells harvested from both medium (3-6 mm) and large (≥8 mm) porcine ovarian follicles. RIA, alamarBlue assay, reverse transcriptase-polymerase chain reaction, and immunocytochemistry were used in the study to address the objectives. Biochanin A significantly inhibited P4 and did not affect E2 secretion by porcine granulosa cells regardless of the size of follicles that served as the source of the cells. Cell viability was not affected by the treatment. Biochanin A did not alter ERα and ERβ mRNA levels in the cultured porcine granulosa cells. In contrast, this isoflavone increased (P < 0.05) the immunoexpression of ERβ in the cells from both follicle types. In summary, biochanin A, similar to genistein and daidzein, affects follicular steroidogenesis and ER expression. Its effect on ERβ protein was more intense compared with other previously examined phytoestrogens. PMID:23953692

  2. Effects of transferrin on aromatase activity in porcine granulosa cells in vitro.

    Directory of Open Access Journals (Sweden)

    Małgorzata Duda

    2009-01-01

    Full Text Available Proliferating cells have an absolute requirement for iron, which is delivered by transferrin with subsequent intracellular transport via the transferrin receptor. Recent studies have reported that transferrin plays a crucial role in the local regulation of ovarian function, apart from its iron-binding characteristic. Therefore, the present study was undertaken to explore the possible role of transferrin in porcine granulosa cells function by examining its influence on aromatase activity, the most important indicator of follicular cell differentiation. In the first series of studies, pig granulosa cells isolated from small, immature follicles were cultured in the presence of transferrin alone (10 microg/ml or 100 microg/ml or with the addition of FSH (100ng/ml. The second series of studies was undertaken to determine transferrin-stimulated granulosa cells ability to aromatize exogenous testosterone (1x10(-7M. One hour after the establishment of cultures an aromatase inhibitor CGS16949A was added to test its influence on estradiol production. After 48 hours, cultures were terminated and cells were processed for immunocytochemical staining of aromatase. Media were frozen for further estradiol level analysis. Positive immunostaining for aromatase was found in all granulosa cell cultures. The intensity of immunostaining was always stronger in cultures supplemented with FSH whereas the addition of transferrin had no effect. Granulosa cells in vitro synthesized the highest amount of estradiol after the addition of FSH and exogenous testosterone as measured radioimmunologically. Concomitant treatment with FSH and transferrin caused an inhibition of FSH-stimulated aromatase activity. The production of estradiol also declined in the presence of FSH, testosterone and transferrin. This study demonstrates that transferrin had a dose-dependent inhibitory effect on FSH-stimulated aromatase activity, which was confirmed by radioimmunoassay. Our results indicate

  3. Spatial differences within the membrana granulosa in the expression of focimatrix and steroidogenic capacity.

    Science.gov (United States)

    Nguyen, Tracy; Lee, Samuel; Hatzirodos, Nicholas; Hummitzsch, Katja; Sullivan, Thomas R; Rodgers, Raymond J; Irving-Rodgers, Helen F

    2012-11-01

    In the ovarian follicular membrana granulosa there are morphological and functional differences between cells adjacent to the follicular fluid lumen, or aligning the basal lamina. Amongst the observed functional differences are steroidogenic capacity and expression levels of a novel basal lamina, focimatrix; both of which increase in the later stages of antral follicle growth. A number of different studies have produced apparently inconsistent results as to which cell layers are more steroidogenic. To examine this systematically, individual bovine follicles, confirmed as healthy by post hoc histological examination, were used to isolate populations of apical and basal granulosa cells. Cell counts revealed that the respective groups did not differ in the numbers of cells, thus confirming the separation of these populations. We measured gene expression (quantitative RT-PCR, n=8-10, follicle diameter 14.0±0.5 mm) and protein levels (Western immunoblotting, n=14, follicle diameter 11.9±0.5 mm) and hormone production from granulosa cells (2.5×10(5) viable cells/well in serum-free conditions for 24 h, n=15, diameter 12±0.5 mm). Levels of mRNA of HSD3B1 and CYP19A1 and three focimatrix genes COL4A1, HSPG2 and LAMB2 and LHCGR were significantly lower in apical granulosa cells (P0.05). The protein levels of steroidogenic enzymes P450scc and P450arom were significantly higher in apical cells (P0.05). Progesterone production was significantly lower and oestradiol production was significantly higher in apical granulosa cells (Pbasal cells are functionally different, and the differences might be explained by the location of cells of different ages and maturity within the membrana granulosa. Discrepancies in the literature on their steroidogenic capacity may reflect differences in the steroidogenic parameters measured. PMID:22863478

  4. Granulosa Cell Tumor Juvenile - Case Report-Primary Care Tumor de Celulas da Granulosa Juvenil - Relato de Caso em Atenção Primária

    Directory of Open Access Journals (Sweden)

    Anelise Olmos Grings

    2010-11-01

    Full Text Available

    The authors given an account of children of 2 years and 4 months with ginaecology complaints (white vaginal secretion, diffuse abdominal pain and early pseudo-puberty. Beginning investigation in Unity of Health Care PSF of Porto Alegre, are refer to the secondary levei was diagnosis ovarian tumor (Juvenile Granulosa Cell Tumor Ovary.

    Os autores relatam o caso de urna criança de 2 anos e 4 meses com queixas ginecológicas (secreção vaginal branca, dor abdominal difusa e pseudopuberdade precoce (telarca. Iniciada investigação em Unidade de Saúde PSF de Porto Alegre, sendo referenciada ao nível secundário onde foi diagnosticada neoplasia ovariana (Tumor de Células da Granulosa Juvenil.

  5. Role of leptin in the regulation of sterol/steroid biosynthesis in goose granulosa cells.

    Science.gov (United States)

    Hu, Shenqiang; Gan, Chao; Wen, Rui; Xiao, Qihai; Gou, Hua; Liu, Hehe; Zhang, Yingying; Li, Liang; Wang, Jiwen

    2014-09-15

    Leptin is critical for reproductive endocrinology. The aim of this study is to assess the expression patterns of leptin receptor (Lepr) during ovarian follicle development and to reveal the mechanism by which leptin affects steroid hormone secretion in goose granulosa cells. Transcripts of Lepr were ubiquitous in all tested tissues, with pituitary and adrenal glands being the predominant sites. Goose ovarian follicles were divided into several groups by diameter including prehierarchical (4 to 6, 6 to 8, and 8 to 10 mm) and hierarchical (F5-F1) follicles. Lepr gene expression was significantly higher in granulosa cells than in theca cells from follicles of 4 to 8 mm in diameter. Expression of Lepr in granulosa cells decreased gradually as follicles developed, with fluctuating expression in F5 and F3 follicles. Lepr mRNA in theca cells underwent a slight decrease from the 6- to 8-mm cohorts to F5 follicle and then exhibited a transient increase and declined later. In vitro experiments in cultured goose granulosa cells showed that estradiol release was significantly stimulated, whereas progesterone increased slightly and testosterone decreased dramatically after leptin treatment. In accordance with the data for steroids, expression of Lepr, Srebp1, Cyp51, StAR, and Cyp19a1 were induced by the addition of leptin, and the concomitant changes in Hmgcs1, Dhcr24, Cyp11a1, 17β-hsd, Cyp17, and 3β-hsd gene expression were seen. These results suggested that leptin is involved in the development of goose ovarian follicles, and leptin's effect on steroid hormone secretion could be due to altered sterol/steroidogenic gene expression via interaction with its receptor. PMID:25016410

  6. Genotoxicity of Superparamagnetic Iron Oxide Nanoparticles in Granulosa Cells.

    Science.gov (United States)

    Pöttler, Marina; Staicu, Andreas; Zaloga, Jan; Unterweger, Harald; Weigel, Bianca; Schreiber, Eveline; Hofmann, Simone; Wiest, Irmi; Jeschke, Udo; Alexiou, Christoph; Janko, Christina

    2015-01-01

    Nanoparticles that are aimed at targeting cancer cells, but sparing healthy tissue provide an attractive platform of implementation for hyperthermia or as carriers of chemotherapeutics. According to the literature, diverse effects of nanoparticles relating to mammalian reproductive tissue are described. To address the impact of nanoparticles on cyto- and genotoxicity concerning the reproductive system, we examined the effect of superparamagnetic iron oxide nanoparticles (SPIONs) on granulosa cells, which are very important for ovarian function and female fertility. Human granulosa cells (HLG-5) were treated with SPIONs, either coated with lauric acid (SEONLA) only, or additionally with a protein corona of bovine serum albumin (BSA; SEON(LA-BSA)), or with dextran (SEON(DEX)). Both micronuclei testing and the detection of γH2A.X revealed no genotoxic effects of SEON(LA-BSA), SEON(DEX) or SEON(LA). Thus, it was demonstrated that different coatings of SPIONs improve biocompatibility, especially in terms of genotoxicity towards cells of the reproductive system. PMID:26540051

  7. Developmental Programming: Does Prenatal Steroid Excess Disrupt the Ovarian VEGF System in Sheep?

    Science.gov (United States)

    Ortega, Hugo Héctor; Veiga-Lopez, Almudena; Sreedharan, Shilpa; del Luján Velázquez, Melisa María; Salvetti, Natalia Raquel; Padmanabhan, Vasantha

    2015-09-01

    Prenatal testosterone (T), but not dihydrotestosterone (DHT), excess disrupts ovarian cyclicity and increases follicular recruitment and persistence. We hypothesized that the disruption in the vascular endothelial growth factor (VEGF) system contributes to the enhancement of follicular recruitment and persistence in prenatal T-treated sheep. The impact of T/DHT treatments from Days 30 to 90 of gestation on VEGFA, VEGFB, and their receptor (VEGFR-1 [FLT1], VEGFR-2 [KDR], and VEGFR-3 [FLT4]) protein expression was examined by immunohistochemistry on Fetal Days 90 and 140, 22 wk, 10 mo (postpubertal), and 21 mo (adult) of age. Arterial morphometry was performed in Fetal Day 140 and postpubertal ovaries. VEGFA and VEGFB expression were found in granulosa cells at all stages of follicular development with increased expression in antral follicles. VEGFA was present in theca interna, while VEGFB was present in theca interna/externa and stromal cells. All three receptors were expressed in the granulosa, theca, and stromal cells during all stages of follicular development. VEGFR-3 increased with follicular differentiation with the highest level seen in the granulosa cells of antral follicles. None of the members of the VEGF family or their receptor expression were altered by age or prenatal T/DHT treatments. At Fetal Day 140, area, wall thickness, and wall area of arteries from the ovarian hilum were larger in prenatal T- and DHT-treated females, suggestive of early androgenic programming of arterial differentiation. This may facilitate increased delivery of endocrine factors and thus indirectly contribute to the development of the multifollicular phenotype. PMID:26178718

  8. Developmental Programming: Does Prenatal Steroid Excess Disrupt the Ovarian VEGF System in Sheep?1

    Science.gov (United States)

    Ortega, Hugo Héctor; Veiga-Lopez, Almudena; Sreedharan, Shilpa; del Luján Velázquez, Melisa María; Salvetti, Natalia Raquel; Padmanabhan, Vasantha

    2015-01-01

    Prenatal testosterone (T), but not dihydrotestosterone (DHT), excess disrupts ovarian cyclicity and increases follicular recruitment and persistence. We hypothesized that the disruption in the vascular endothelial growth factor (VEGF) system contributes to the enhancement of follicular recruitment and persistence in prenatal T-treated sheep. The impact of T/DHT treatments from Days 30 to 90 of gestation on VEGFA, VEGFB, and their receptor (VEGFR-1 [FLT1], VEGFR-2 [KDR], and VEGFR-3 [FLT4]) protein expression was examined by immunohistochemistry on Fetal Days 90 and 140, 22 wk, 10 mo (postpubertal), and 21 mo (adult) of age. Arterial morphometry was performed in Fetal Day 140 and postpubertal ovaries. VEGFA and VEGFB expression were found in granulosa cells at all stages of follicular development with increased expression in antral follicles. VEGFA was present in theca interna, while VEGFB was present in theca interna/externa and stromal cells. All three receptors were expressed in the granulosa, theca, and stromal cells during all stages of follicular development. VEGFR-3 increased with follicular differentiation with the highest level seen in the granulosa cells of antral follicles. None of the members of the VEGF family or their receptor expression were altered by age or prenatal T/DHT treatments. At Fetal Day 140, area, wall thickness, and wall area of arteries from the ovarian hilum were larger in prenatal T- and DHT-treated females, suggestive of early androgenic programming of arterial differentiation. This may facilitate increased delivery of endocrine factors and thus indirectly contribute to the development of the multifollicular phenotype. PMID:26178718

  9. Primary juxtaovarian yolk sac tumor concurrent with an ipsilateral ovarian mature teratoma in an adult woman: a rare association

    OpenAIRE

    Ma, Haifen; Yu, Jihong; Tang, Jingjing; Wang, Min

    2015-01-01

    Objectives: Yolk sac tumor (YST) is a rare neoplasm that primarily occurs in the ovary in children and young women. Previously, it has been reported that the teratomatous components can be recognized in part of YSTs or appear in the contralateral ovary. Here, we report a rare case of an adult woman with a juxtaovarian YST concurrent with an ipsilateral ovarian mature teratoma. Methods: A 47-year-old woman found a pelvic mass for nine days and subsequently underwent debulking operation. The sp...

  10. Breeding biology and microhabitat utilization of the intertidal isopod Idotea granulosa Rathke, in the Irish Sea

    Science.gov (United States)

    Salemaa, Heikki

    1986-03-01

    The life history and distribution of the intertidal isopod Idotea granulosa were investigated at five rocky shore biotopes in the Isle of Man. I. granulosa breeds throughout the year in the Irish Sea. The breeding activity is highest in the early summer after the sexual maturation of the overwintered animals. At that period about 4% of the females were infested by Clypeoniscus sp. (Isopoda) which destroys the brood. A small proportion of the juveniles released in the early summer mature and breed in the autumn. In the winter Idotea populations consisted of juveniles, immature adults and old individuals which produce another brood. These large sized animals die off before the summer. Consequently, the age and size of the breeding I. granulosa fluctuates seasonally. The number of eggs is linearly related to the female length. The fecundity is highest in the spring and lowest in the autumn in all female size classes. I. granulosa inhabits an array of structurally different intertidal algae including the filamentous Cladophora rupestris, understory turfs Gigartina stellata, Laurencia pinnatifida and Corallina officinalis and the fucoids Fucus serratus and Ascophyllum nodosum. The distribution pattern of I. granulosa in examined intertidal communities is modified by the physiognomy of the algal microhabitats, by seasonal and spatial variation in wave agitation and by the breeding cycle of the population itself. Both the life history characteristics and distribution patterns are explained as adaptations to the spatially and temporally heterogeneous intertidal shores.

  11. Paracrine Regulation of Steroidogenesis in Theca Cells by Granulosa Cells Derived from Mouse Preantral Follicles

    Directory of Open Access Journals (Sweden)

    Xiaoqiang Liu

    2015-01-01

    Full Text Available Interaction partners of follicular cells play a significant role in steroidogenesis, follicular formation, and development. Androgen secreted by theca cells (TCs can initiate follicle development and ovulation and provide precursor materials for estrogen synthesis. Therefore, studies on ovarian microenvironment will not only lead to better understanding of the steroidogenesis but also have clinical significance for ovarian endocrine abnormalities such as hyperandrogenism in polycystic ovary syndrome (PCOS. This study applied the Transwell coculture model to investigate if the interaction between granulosa and theca cells may affect androgen production in theca cells. Concentrations of testosterone and androstenedione in the spent medium were measured by radioimmunoassay and enzyme linked immunosorbent assay, respectively. The results show that the coculture with granulosa cells (GCs increases steroidogenesis in TCs. In addition, testosterone and androstenedione productions in response to LH stimulation were also increased in the coculture model. Significantly increased mRNA expressions of steroidogenic enzymes (Star, Cyp11a1, Cyp17a1, and Hsd3b2 were observed in the cocultured TCs. Thus, GCs were capable of promoting steroidogenesis and LH responsiveness in TCs. This study provided a basis for further exploration of ovarian endocrine mechanism and pathologies.

  12. Ovarian Follicle Ultrastructure and Changes in Levels of Ovarian Steroids during Oogenesis in Chalcalburnus tarichi Pallas, 1811

    OpenAIRE

    ÜNAL, Güler

    2005-01-01

    The ultrastructure of the ovarian follicle and the levels of the ovarian 11-dehydrocorticosterone (11-DHC), estradiol-17b (E2), 17a-hydroxyprogesterone (17a-OHP), and progesterone (P) were studied during cortical alveoli, vitellogenesis and oocyte maturation in Chalcalburnus tarichi. The microvilli began to form on the oocyte surface during cortical alveoli phase and during vitellogenesis, came into contact in the pore canals of the zona radiata with microvilli formed from granulosa cells. Wh...

  13. Regional-specific effects of ovarian hormone loss on synaptic plasticity in adult human APOE targeted replacement mice.

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    Rebecca C Klein

    Full Text Available The human apolipoprotein ε4 allele (APOE4 has been implicated as one of the strongest genetic risk factors associated with Alzheimer's disease (AD and in influencing normal cognitive functioning. Previous studies have demonstrated that mice expressing human apoE4 display deficits in behavioral and neurophysiological outcomes compared to those with apoE3. Ovarian hormones have also been shown to be important in modulating synaptic processes underlying cognitive function, yet little is known about how their effects are influenced by apoE. In the current study, female adult human APOE targeted replacement (TR mice were utilized to examine the effects of human APOE genotype and long-term ovarian hormone loss on synaptic plasticity in limbic regions by measuring dendritic spine density and electrophysiological function. No significant genotype differences were observed on any outcomes within intact mice. However, there was a significant main effect of genotype on total spine density in apical dendrites in the hippocampus, with post-hoc t-tests revealing a significant reduction in spine density in apoE3 ovariectomized (OVX mice compared to sham operated mice. There was also a significant main effect of OVX on the magnitude of LTP, with post-hoc t-tests revealing a decrease in apoE3 OVX mice relative to sham. In contrast, apoE4 OVX mice showed increased synaptic activity relative to sham. In the lateral amygdala, there was a significant increase in total spine density in apoE4 OVX mice relative to sham. This increase in spine density was consistent with a significant increase in spontaneous excitatory activity in apoE4 OVX mice. These findings suggest that ovarian hormones differentially modulate synaptic integrity in an apoE-dependent manner within brain regions that are susceptible to neurophysiological dysfunction associated with AD.

  14. Immunoregulation of follicular renewal, selection, POF, and menopause in vivo, vs. neo-oogenesis in vitro, POF and ovarian infertility treatment, and a clinical trial

    Directory of Open Access Journals (Sweden)

    Bukovsky Antonin

    2012-11-01

    Full Text Available Abstract The immune system plays an important role in the regulation of tissue homeostasis ("tissue immune physiology". Function of distinct tissues during adulthood, including the ovary, requires (1 Renewal from stem cells, (2 Preservation of tissue-specific cells in a proper differentiated state, which differs among distinct tissues, and (3 Regulation of tissue quantity. Such morphostasis can be executed by the tissue control system, consisting of immune system-related components, vascular pericytes, and autonomic innervation. Morphostasis is established epigenetically, during morphogenetic (developmental immune adaptation, i.e., during the critical developmental period. Subsequently, the tissues are maintained in a state of differentiation reached during the adaptation by a “stop effect” of resident and self renewing monocyte-derived cells. The later normal tissue is programmed to emerge (e.g., late emergence of ovarian granulosa cells, the earlier its function ceases. Alteration of certain tissue differentiation during the critical developmental period causes persistent alteration of that tissue function, including premature ovarian failure (POF and primary amenorrhea. In fetal and adult human ovaries the ovarian surface epithelium cells called ovarian stem cells (OSC are bipotent stem cells for the formation of ovarian germ and granulosa cells. Recently termed oogonial stem cells are, in reality, not stem but already germ cells which have the ability to divide. Immune system-related cells and molecules accompany asymmetric division of OSC resulting in the emergence of secondary germ cells, symmetric division, and migration of secondary germ cells, formation of new granulosa cells and fetal and adult primordial follicles (follicular renewal, and selection and growth of primary/preantral, and dominant follicles. The number of selected follicles during each ovarian cycle is determined by autonomic innervation. Morphostasis is altered with

  15. Immunoregulation of follicular renewal, selection, POF, and menopause in vivo, vs. neo-oogenesis in vitro, POF and ovarian infertility treatment, and a clinical trial.

    Science.gov (United States)

    Bukovsky, Antonin; Caudle, Michael R

    2012-11-23

    The immune system plays an important role in the regulation of tissue homeostasis ("tissue immune physiology"). Function of distinct tissues during adulthood, including the ovary, requires (1) Renewal from stem cells, (2) Preservation of tissue-specific cells in a proper differentiated state, which differs among distinct tissues, and (3) Regulation of tissue quantity. Such morphostasis can be executed by the tissue control system, consisting of immune system-related components, vascular pericytes, and autonomic innervation. Morphostasis is established epigenetically, during morphogenetic (developmental) immune adaptation, i.e., during the critical developmental period. Subsequently, the tissues are maintained in a state of differentiation reached during the adaptation by a "stop effect" of resident and self renewing monocyte-derived cells. The later normal tissue is programmed to emerge (e.g., late emergence of ovarian granulosa cells), the earlier its function ceases. Alteration of certain tissue differentiation during the critical developmental period causes persistent alteration of that tissue function, including premature ovarian failure (POF) and primary amenorrhea. In fetal and adult human ovaries the ovarian surface epithelium cells called ovarian stem cells (OSC) are bipotent stem cells for the formation of ovarian germ and granulosa cells. Recently termed oogonial stem cells are, in reality, not stem but already germ cells which have the ability to divide. Immune system-related cells and molecules accompany asymmetric division of OSC resulting in the emergence of secondary germ cells, symmetric division, and migration of secondary germ cells, formation of new granulosa cells and fetal and adult primordial follicles (follicular renewal), and selection and growth of primary/preantral, and dominant follicles. The number of selected follicles during each ovarian cycle is determined by autonomic innervation. Morphostasis is altered with advancing age, due to

  16. Development of the membrana granulosa of bovine antral follicles: structure, location of mitosis and pyknosis, and immunolocalization of involucrin and vimentin.

    Science.gov (United States)

    van Wezel, I L; Krupa, M; Rodgers, R J

    1999-01-01

    The membrana granulosa of the ovarian follicle is termed the 'follicular epithelium', yet there have been no studies considering its epithelial nature and how it changes during follicular development. Therefore, these issues were investigated using histology (n = 45 ovaries), considering its structure and the location of proliferating and dying cells, and drawing analogies with other epithelia. Additionally, differences between the layers of granulosa cells were demonstrated by immunohistochemistry (n = 7 ovaries). The structure of the membrana granulosa differed between follicles. Six arbitrary classifications were designed based on these structures, 80 follicles were allocated (n = 13 ovaries) to these classes and the follicular diameters were then measured. For the first time, differences in membrana granulosa structure were shown to correspond to follicle size. Follicles in classes 1-3, where basal granulosa cells were columnar with nuclei positioned basally in the cell, were all basal cells with nuclei positioned centrally (class 4), or had rounded basal cells (class 5), and all follicles > 5 mm had only rounded basal cells. In all these classes, cells in the middle zone were rounded; cells aligning the antrum were often flattened. Irrespective of follicle class, cell proliferation and cell death were shown to be predominantly in the middle portions, rather than the most antral or most basal portions, of the membrana granulosa of healthy and atretic follicles. Involucrin, a marker of keratinocyte differentiation, was localized to the suprabasal region of the membrana granulosa of healthy follicles, particularly in the second and third cellular layers in from the follicular basal lamina. Conversely, the staining intensity for the intermediate filament protein vimentin was lowest in this region, and greatest in the more antral and basal regions. In atretic follicles, there was widespread staining for involucrin and vimentin throughout the membrana granulosa. In

  17. Genetic changes in nonepithelial ovarian cancer.

    Science.gov (United States)

    Van Nieuwenhuysen, Els; Lambrechts, Sandrina; Lambrechts, Diether; Leunen, Karin; Amant, Frédéric; Vergote, Ignace

    2013-07-01

    Nonepithelial ovarian cancers (OCs), including sex cord-stromal tumors (SCSTs) and germ cell tumors (GCTs), are an uncommon subset of OC, together accounting for 10% of all OCs. The etiology of these tumors remains largely unresolved. It is well established that tumorigenesis is the result of multiple genetic alterations driving a normal cell toward a malignant state. Much effort has been made into researching the molecular mechanisms underlying epithelial OC, but far less is known about the genetic changes in SCSTs and GCTs. Recently, a single point missense mutation (C134W) was found in the FOXL2 gene in approximately 95% of adult-type granulosa cell tumors, suggesting a key role for FOXL2 in these tumors. By contrast, the FOXL2 mutation was not found in the juvenile type. DICER1 somatic missense mutations were found in approximately 60% of Sertoli-Leydig tumors. Ovarian GCTs share many morphological features and a similar pattern of chromosomal alterations with testicular GCTs. In the latter, recent genome-wide association studies have identified seven susceptibility loci near KITLG, SPRY4, UKC2, BAK1, DMRT1, TERT and ATF7IP. All of the susceptibility loci detected thus far are all involved in primordial germ cell function or sex determination. TGF-β/BMP and Wnt/β-catenin signaling was absent in dysgerminomas, but present in yolk sac tumors, suggesting intertumoral heterogeneity. In this article, the authors aim to provide an overview of the current knowledge on the possible molecular changes in SCSTs and GCTs of the ovary. PMID:23875665

  18. Oocyte-granulosa cell interactions during mouse follicular development: regulation of kit ligand expression and its role in oocyte growth

    Directory of Open Access Journals (Sweden)

    Vanderhyden Barbara C

    2006-04-01

    Full Text Available Abstract Ovarian folliculogenesis is regulated by both endocrine and intraovarian mechanisms that coordinate the processes of oocyte growth and somatic cell proliferation and differentiation. Within the follicle, paracrine interactions between the oocyte and surrounding granulosa cells are critical for normal cell development and function. This review focuses on the role of paracrine interactions during early oocyte and follicular development that ensure proper coordination of oocyte and somatic cell function. Particular emphasis is given to granulosa cell-derived Kit Ligand (KitL, whose functional importance for oocyte growth has been demonstrated by a wide range of in vivo and in vitro studies. Reported interactions between KitL and oocyte-derived growth differentiation factor-9 (GDF9 and bone morphogenetic protein-15 (BMP15 suggest the molecular basis of oocyte-granulosa cell interactions, but also hint at the complexity of these communications. These paracrine interactions and the structure of the oocyte-granulosa cell interface are follicle stage-specific and regulated by FSH. Elucidation of the molecular mechanisms that promote the development of healthy oocytes with good developmental competence has potential applications for improving fertility and for in vitro growth systems for oocytes from domestic animals and humans.

  19. A computational model to predict rat ovarian steroid secretion from in vitro experiments with endocrine disruptors.

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    Nadia Quignot

    Full Text Available A finely tuned balance between estrogens and androgens controls reproductive functions, and the last step of steroidogenesis plays a key role in maintaining that balance. Environmental toxicants are a serious health concern, and numerous studies have been devoted to studying the effects of endocrine disrupting chemicals (EDCs. The effects of EDCs on steroidogenic enzymes may influence steroid secretion and thus lead to reproductive toxicity. To predict hormonal balance disruption on the basis of data on aromatase activity and mRNA level modulation obtained in vitro on granulosa cells, we developed a mathematical model for the last gonadal steps of the sex steroid synthesis pathway. The model can simulate the ovarian synthesis and secretion of estrone, estradiol, androstenedione, and testosterone, and their response to endocrine disruption. The model is able to predict ovarian sex steroid concentrations under normal estrous cycle in female rat, and ovarian estradiol concentrations in adult female rats exposed to atrazine, bisphenol A, metabolites of methoxychlor or vinclozolin, and letrozole.

  20. Granulosin, a new chromone from Galipea granulosa.

    Science.gov (United States)

    Lpez, J A; Barillas, W; Gomez-Laurito, J; Martin, G E; Al-Rehaily, A J; Zemaitis, M A; Schiff, P L

    1997-01-01

    A novel chromone, granulosin (1), has been isolated from the bark of Galipea granulosa. The extract of the bark, as well as granulosin (1), exhibited lethality in the brine shrimp test. The structure of granulosin (1) as 2-propyl-7,8-(methylenedioxy)chromone was established via spectroscopic analysis. PMID:9064364

  1. Insulin signalling and glucose transport in the ovary and ovarian function during the ovarian cycle.

    Science.gov (United States)

    Dupont, Joëlle; Scaramuzzi, Rex J

    2016-06-01

    Data derived principally from peripheral tissues (fat, muscle and liver) show that insulin signals via diverse interconnecting intracellular pathways and that some of the major intersecting points (known as critical nodes) are the IRSs (insulin receptor substrates), PI3K (phosphoinositide kinase)/Akt and MAPK (mitogen-activated protein kinase). Most of these insulin pathways are probably also active in the ovary and their ability to interact with each other and also with follicle-stimulating hormone (FSH) and luteinizing hormone (LH) signalling pathways enables insulin to exert direct modulating influences on ovarian function. The present paper reviews the intracellular actions of insulin and the uptake of glucose by ovarian tissues (granulosa, theca and oocyte) during the oestrous/menstrual cycle of some rodent, primate and ruminant species. Insulin signals through diverse pathways and these are discussed with specific reference to follicular cell types (granulosa, theca and oocyte). The signalling pathways for FSH in granulosa cells and LH in granulosa and theca cells are summarized. The roles of glucose and of insulin-mediated uptake of glucose in folliculogenesis are discussed. It is suggested that glucose in addition to its well-established role of providing energy for cellular function may also have insulin-mediated signalling functions in ovarian cells, involving AMPK (AMP-dependent protein kinase) and/or hexosamine. Potential interactions of insulin signalling with FSH or LH signalling at critical nodes are identified and the available evidence for such interactions in ovarian cells is discussed. Finally the action of the insulin-sensitizing drugs metformin and the thiazolidinedione rosiglitazone on follicular cells is reviewed. PMID:27234585

  2. Intact fetal ovarian cord formation promotes mouse oocyte survival and development

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    Pera Renee

    2010-01-01

    Full Text Available Abstract Background Female reproductive potential, or the ability to propagate life, is limited in mammals with the majority of oocytes lost before birth. In mice, surviving perinatal oocytes are enclosed in ovarian follicles for subsequent oocyte development and function in the adult. Before birth, fetal germ cells of both sexes develop in clusters, or germline cysts, in the undifferentiated gonad. Upon sex determination of the fetal gonad, germ cell cysts become organized into testicular or ovarian cord-like structures and begin to interact with gonadal somatic cells. Although germline cysts and testicular cords are required for spermatogenesis, the role of cyst and ovarian cord formation in mammalian oocyte development and female fertility has not been determined. Results Here, we examine whether intact fetal ovarian germ and somatic cell cord structures are required for oocyte development using mouse gonad re-aggregation and transplantation to disrupt gonadal organization. We observed that germ cells from disrupted female gonad prior to embryonic day e13.5 completed prophase I of meiosis but did not survive following transplantation. Furthermore, re-aggregated ovaries from e13.5 to e15.5 developed with a reduced number of oocytes. Oocyte loss occurred before follicle formation and was associated with an absence of ovarian cord structure and ovary disorganization. However, disrupted ovaries from e16.5 or later were resistant to the re-aggregation impairment and supported robust oocyte survival and development in follicles. Conclusions Thus, we demonstrate a critical window of oocyte development from e13.5 to e16.5 in the intact fetal mouse ovary, corresponding to the establishment of ovarian cord structure, which promotes oocyte interaction with neighboring ovarian somatic granulosa cells before birth and imparts oocytes with competence to survive and develop in follicles. Because germline cyst and ovarian cord structures are conserved in the

  3. Exosomal miR-10a derived from amniotic fluid stem cells preserves ovarian follicles after chemotherapy

    OpenAIRE

    Guan-Yu Xiao; Chun-Chun Cheng; Yih-Shien Chiang; Winston Teng-Kuei Cheng; I-Hsuan Liu; Shinn-Chih Wu

    2016-01-01

    Chemotherapy (CTx)-induced premature ovarian failure (POF) in woman remains clinically irreversible. Amniotic fluid stem cells (AFSCs) have shown the potential to treat CTx-induced POF; however, the underlying mechanism is unclear. Here we demonstrate that AFSC-derived exosomes recapitulate the anti-apoptotic effect of AFSCs on CTx-damaged granulosa cells (GCs), which are vital for the growth of ovarian follicles. AFSC-derived exosomes prevent ovarian follicular atresia in CTx-treated mice vi...

  4. Interleukin-1 (IL-1 system gene expression in granulosa cells: kinetics during terminal preovulatory follicle maturation in the mare

    Directory of Open Access Journals (Sweden)

    Gérard Nadine

    2003-05-01

    Full Text Available Abstract Background A growing body of evidences suggests that the ovary is a site of inflammatory reactions, and thus, ovarian cells could represent sources and targets of the interleukin-1 (IL-1 system. The purpose of this study was to examine the IL-1 system gene expressions in equine granulosa cells, and to study the IL-1β content in follicular fluid during the follicle maturation. For this purpose, granulosa cells and follicular fluids were collected from the largest follicle at the early dominance stage (diameter 24 ± 3 mm or during the preovulatory maturation phase, at T0 h, T6 h, T12 h, T24 h and T34 h after induction of ovulation. Cells were analysed by RT-PCR and follicular fluids were studied by gel electrophoresis and immunoblotting. Results We demonstrated that interleukin-1β (IL-1β, interleukin-1 receptor 2 (IL-1R2 and interleukin-1 receptor antagonist (IL-1RA genes are expressed in equine granulosa cells. We observed that the IL-1β and IL-1RA mRNA content changed in granulosa cells during the terminal follicular maturation whereas IL-1R2 mRNA did not vary. In follicular fluid, IL-1β content fluctuated few hours after induction of ovulation. Conclusions The expression of IL-1β gene in granulosa cells and the follicular fluid IL-1β content seem to be regulated by gonadotropins suggesting that IL-1β could be an intermediate paracrine factor involved in ovulation.

  5. Ovotoxic effects of galactose involve attenuation of follicle-stimulating hormone bioactivity and up-regulation of granulosa cell p53 expression.

    Directory of Open Access Journals (Sweden)

    Sayani Banerjee

    Full Text Available Clinical evidence suggests an association between galactosaemia and premature ovarian insufficiency (POI; however, the mechanism still remains unresolved. Experimental galactose toxicity in rats produces an array of ovarian dysfunction including ovarian development with deficient follicular reserve and follicular resistance to gonadotrophins that characterize the basic tenets of human POI. The present investigation explores if galactose toxicity in rats attenuates the bioactivity of gonadotrophins or interferes with their receptor competency, and accelerates the rate of follicular atresia. Pregnant rats were fed isocaloric food-pellets supplemented with or without 35% D-galactose from day-3 of gestation and continuing through weaning of the litters. The 35-day old female litters were autopsied. Serum galactose-binding capacity, galactosyltransferase (GalTase activity, and bioactivity of FSH and LH together with their receptor competency were assessed. Ovarian follicular atresia was evaluated in situ by TUNEL. The in vitro effects of galactose were studied in isolated whole follicles in respect of generation of reactive oxygen species (ROS and expression of caspase 3, and in isolated granulosa cells in respect of mitochondrial membrane potential, expression of p53, and apoptosis. The rats prenatally exposed to galactose exhibited significantly decreased serum GalTase activity and greater degree of galactose-incorporation capacity of sera proteins. LH biopotency and LH-FSH receptor competency were comparable between the control and study population, but the latter group showed significantly attenuated FSH bioactivity and increased rate of follicular atresia. In culture, galactose increased follicular generation of ROS and expression of caspase 3. In isolated granulosa cells, galactose disrupted mitochondrial membrane potential, stimulated p53 expression, and induced apoptosis in vitro; however co-treatment with either FSH or estradiol

  6. Ovarian actions of resveratrol.

    Science.gov (United States)

    Ortega, Israel; Duleba, Antoni J

    2015-08-01

    Resveratrol, a natural polyphenol found in grapes, berries, and medicinal plants, exhibits antioxidant and anti-inflammatory activities and has been proposed to be a longevity-prolonging agent. There is also growing evidence that resveratrol has cardioprotective properties and beneficial effects on both glucose and lipid metabolism. Recently, several studies have examined the use of resveratrol as a therapeutic agent to treat numerous pathological and metabolic disorders. Herein, we present insights into the mechanisms of action, biological effects, and current evidence of actions of resveratrol on the ovary. In vitro, resveratrol inhibits proliferation and androgen production by theca-interstitial cells. Resveratrol also exerts a cytostatic, but not cytotoxic, effect on granulosa cells, while decreasing aromatization and vascular endothelial growth factor expression. In vivo, resveratrol treatment reduced the size of adipocytes and improved estrus cyclicity in the previously acyclic rat model of polycystic ovary syndrome (PCOS). In addition, resveratrol increased the ovarian follicular reserve and prolonged the ovarian life span in rats. Taken together, resveratrol emerges as a potential therapeutic agent to treat conditions associated with androgen excess, such as PCOS. The efficacy of resveratrol in the treatment of gynecological conditions requires further investigation. PMID:26315293

  7. Bisphenol A and ovarian steroidogenesis.

    Science.gov (United States)

    Bloom, Michael S; Mok-Lin, Evelyn; Fujimoto, Victor Y

    2016-09-15

    Bisphenol A is widely used as a component in polycarbonate plastics for food and beverage packaging, epoxy linings for canned foods, and dental sealants, among other applications. Experimental literature demonstrates BPA's affinity for estrogen receptors and downstream effects on estrogen-responsive genes. Additional data suggest that BPA reduces endogenous estrogen synthesis, likely by antagonizing ovarian enzyme activities involved in sex-steroid hormone synthesis. More specifically, evidence indicates BPA-mediated disruption of STAR, CYP450scc, and HSD-3β in theca cells and CYP450 aromatase activity in granulosa cells. Yet the results of the few human studies reported to date are equivocal. It also remains in question the extent to which BPA penetrates developing ovarian follicles. Uncertainty as to the relevance of experimental BPA doses and administration routes for common human exposure levels limits extrapolation of experimental results. To more definitively address the potential risk of BPA on human ovarian steroidogenesis, additional experimental studies using biologically active BPA doses likely to reflect those within the ovarian follicle will be necessary, as will additional prospective investigations in human populations with the use of standardized assay methodology. PMID:27543890

  8. Gene expression profiling bovine ovarian follicular and luteal cells provides insight into cellular identities and functions

    Science.gov (United States)

    After ovulation, somatic cells of the ovarian follicle (theca and granulosa cells) become the small and large luteal cells of the corpus luteum. Aside from known cell type-specific receptors and steroidogenic enzymes, little is known about the differences in the gene expression profiles of these fou...

  9. Apoptosis in Granulosa cells during follicular atresia:relationship with steroids and insulin-like growth factors

    Institute of Scientific and Technical Information of China (English)

    Yuan Song YU; Hong Shu SUI; Zheng Bin HAN; Wei LI; Ming Jiu LUO; Jing He TAN

    2004-01-01

    It is well known that during mammalian ovarian follicular development, the majority of follicles undergo atresia at various stages of their development. However, the mechanisms controlling this selection process remain unknown. In this study, we investigated apoptosis in granulosa cells during goat follicular atresia by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The changes in the levels of steroids, insulin-like growth factors (IGFs) and IGF receptors were studied by radioimmunoassay (RIA) and semi-quantitative reverse transcription-PCR. We found that the percentage of apoptotic granulosa cells in the atretic (A) follicles was significantly higher than that in the slightly atretic (SA) and healthy (H) follicles. The level of estradiol and the ratio of estradiol to progesterone in H follicles were significantly higher than those in A follicles. On the other hand, the level of progesterone was not significantly different among these follicle types. We also found that the level of IGF-I in H follicles was higher than in SA and A follicles, whereas the amount of IGF-Ⅱ did not vary significantly. The expression of IGF receptor also decreased in A follicles as compared to that in H and SA follicles. These results suggested that estradiol and IGF-I might be involved in controlling apoptosis in granulosa cells during follicular atresia.

  10. Evaluation of steroidogenic capacity after follicle stimulating hormone stimulation in bovine granulosa cells of Revalor 200® implanted heifers

    Institute of Scientific and Technical Information of China (English)

    Andrea DStapp; Craig AGifford; Dennis MHallford; Jennifer AHernandez Gifford

    2014-01-01

    Background:Heifers not used as breeding stock are often implanted with steroids to increase growth efficiency thereby altering hormone profiles and potentially changing the environment in which ovarian follicles develop. Because bovine granulosa cell culture is a commonly used technique and often bovine ovaries are collected from abattoirs with no record of implant status, the objective of this study was to determine if the presence of an implant during bovine granulosa cell development impacts follicle stimulating hormone-regulated steroidogenic enzyme expression. Paired ovaries were collected from 16 feedlot heifers subjected to 1 of 3 treatments:non-implanted (n=5), Revalor 200 for 28 d (n=5), or Revalor 200 for 84 d (n=6). Small follicle (1 to 5 mm) granulosa cells were isolated from each pair and incubated with phosphate buffered saline (n=16) or 100 ng/mL follicle stimulating hormone (n=16) for 24 h. Results:Granulosa cells of implanted heifers treated with follicle stimulating hormone produced medium concentrations of progesterone similar (P=0.22) to non-implanted heifers, while medium estradiol concentrations were increased (P<0.10) at 28 and 84 d compared to non-implanted heifers indicating efficacy of treatment. Additionally, real-time PCR analysis in response to follicle stimulating hormone treatment demonstrated a decrease in steroidogenic acute regulatory protein (P=0.05) mRNA expression in heifers implanted for 84 d and an increase in P450 side chain cleavage mRNA in granulosa cells of heifers implanted for 28 (P<0.10) or 84 d (P<0.05) compared to non-implanted females. However, no difference in expression of 3-beta-hydroxysteroid dehydrogenase (P=0.57) and aromatase (P=0.23) were demonstrated in implanted or non-implanted heifers. Conclusions:These results indicate follicles which develop in the presence of high concentrations of androgenic and estrogenic steroids via an implant tend to demonstrate an altered capacity to respond to follicle

  11. Alfa-fetoprotein secreting ovarian sex cord-stromal tumor

    Directory of Open Access Journals (Sweden)

    Kusum D Jashnani

    2013-01-01

    Full Text Available Ovarian sex cord-stromal tumors are relatively infrequent neoplasms that account for approximately 8% of all primary ovarian tumors. They are a heterogeneous group of neoplasms composed of cells derived from gonadal sex cords (granulosa and Sertoli cells, specialized gonadal stroma (theca and Leydig cells, and fibroblasts. They may show androgenic or estrogenic manifestations. We report such a tumor associated with markedly raised serum alpha-fetoprotein (AFP levels in a young female presenting with a mass and defeminising symptoms. Serum AFP levels returned to normal on removal of tumor.

  12. Ultrastructure of isolated mouse ovarian follicles cultured in vitro

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    Rossi Gianna

    2011-01-01

    Full Text Available Abstract Background In vitro maturation of ovarian follicles, in combination with cryopreservation, might be a valuable method for preserving and/or restoring fertility in mammals with impaired reproductive function. Several culture systems capable of sustaining mammalian follicle growth in vitro have been developed and many studies exist on factors influencing the development of in vitro grown oocytes. However, a very few reports concern the ultrastructural morphology of in vitro grown follicles. Methods The present study was designed to evaluate, by transmission and scanning electron microscopy, the ultrastructural features of isolated mouse preantral follicles cultured in vitro for 6 days in a standard medium containing fetal calf serum (FCS. The culture was supplemented or not with FSH. Results The follicles cultured in FCS alone, without FSH supplementation (FCS follicles, did not form the antral cavity. They displayed low differentiation (juxta-nuclear aggregates of organelles in the ooplasm, a variable amount of microvilli on the oolemma, numerous granulosa cell-oolemma contacts, signs of degeneration in granulosa cell compartment. Eighty (80% of FSH-treated follicles formed the antral cavity (FSH antral follicles. These follicles showed various ultrastructural markers of maturity (spreading of organelles in ooplasm, abundant microvilli on the oolemma, scarce granulosa cell-oolemma contacts, granulosa cell proliferation. Areas of detachment of the innermost granulosa cell layer from the oocyte were also found, along with a diffuse granulosa cell loosening compatible with the antral formation. Theca cells showed an immature morphology for the stage reached. Twenty (20% of FSH-treated follicles did not develop the antral cavity (FSH non-antral follicles and displayed morphological differentiation features intermediate between those shown by FCS and FSH antral follicles (spreading of organelles in the ooplasm, variable amount of microvilli

  13. MR findings of ovarian tumors with hormonal activity, with emphasis on tumors other than sex cord-stromal tumors

    International Nuclear Information System (INIS)

    Sex cord-stromal tumors including granulosa cell tumor, thecoma, Sertoli stromal cell tumor and steroid cell tumor are noted for their hormonal activity. However, there are many kinds of ovarian tumors other than sex cord-stromal tumors and tumor-like conditions with endocrine manifestations. Cross-sectional imaging, especially MR, can provide precise features of ovarian tumors and uterine morphological change even in a clinically latent excess of estrogen. In this article, we demonstrate typical imaging findings of ovarian tumors with hormonal activity. We also shortly explain the mechanism of the virilization and hyperestrogenism caused by ovarian tumors and tumor-like conditions

  14. EFFECT OF NATURAL PLANT EXTRACTS ON PORCINE OVARIAN FUNCTIONS

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    Attila Kádasi

    2015-02-01

    Full Text Available This report provides information about the impact of chosen natural plant extracts on basic ovarian functions. This article summarizes our results concerning the effect of selected plant extracts on proliferation, apoptosis and hormone secretion – release of progesterone (P4, testosterone (T and leptin (L on porcine granulosa cells (GC, We analyzed effects of ginkgo (GB, rooibos (RB, flaxseed (FL, green tea polyphenols (GTPP, green tea - epigallocatechin-3-gallate (EGCG, resveratrol (RSV and curcumin (CURC (0; 1; 10 and 100 μg.ml-1 on markers of proliferation, apoptosis and secretory activity of porcine ovarian granulosa cells by using immunocytochemistry and EIA. It was demonstrated, that all these natural plants and plant molecules inhibited the accumulation of proliferation-related peptide (PCNA and apoptosis-associated peptide (Bax in cultured. Furthermore, it was observed that natural plant extracts altered progesterone, testosterone and leptin release in porcine ovarian cells. It is concluded, that GB, RB, FL, RSV, CURC, GTPP and EGCG can directly affect ovarian cells and therefore they could potentially influence ovarian functions.

  15. Ovarian reserve

    NARCIS (Netherlands)

    Macklon, NS; Fauser, BCJM

    2005-01-01

    The tendency to delay childbirth has increased the importance of ovarian reserve as a determinant of infertility treatment outcome. In the context of assisted reproduction technology, effective strategies to overcome the impact of ovarian aging and diminished ovarian reserve on pregnancy chances rem

  16. Granulosa cells and retinoic acid co-treatment enrich potential germ cells from manually selected Oct4-EGFP expressing human embryonic stem cells.

    Science.gov (United States)

    Chen, Hsin-Fu; Jan, Pey-Shynan; Kuo, Hung-Chih; Wu, Fang-Chun; Lan, Chen-Wei; Huang, Mei-Chi; Chien, Chung-Liang; Ho, Hong-Nerng

    2014-09-01

    Differentiation of human embryonic stem (HES) cells to germ cells may become clinically useful in overcoming diseases related to germ-cell development. Niches were used to differentiate HES cell lines, NTU1 and H9 Oct4-enhanced green fluorescence protein (EGFP), including laminin, granulosa cell co-culture or conditioned medium, ovarian stromal cell co-culture or conditioned medium, retinoic acid, stem cell factor (SCF) and BMP4-BMP7-BMP8b treatment. Flow cytometry showed that granulosa cell co-culture (P cells expressing early germ cell marker stage-specific embryonic antigen 1(SSEA1); sorted SSEA1[+] cells did not express higher levels of germ cell gene VASA and GDF9. Manually collected H9 Oct4-EGFP[+] cells expressed significantly higher levels of VASA (P = 0.005) and GDF9 (P = 0.001). H9 Oct4-EGFP[+] cells developed to ovarian follicle-like structures after culture for 28 days but with low efficiency. Unlike SCF and BMP4, retinoic acid co-treatment enhanced VASA, GDF9 and SCP3 expression. A protocol is recommended to enrich differentiated HES cells with germ-cell potential by culture with granulosa cells, conditioned medium or retinoic acid, manual selection of Oct4-EGFP[+] cells, and analysis of VASA, GDF9 expression, or both.

  17. Effect of epidermal growth factor on follicle-stimulating hormone-induced proliferation of granulosa cells from chicken prehierarchical follicles

    Institute of Scientific and Technical Information of China (English)

    Jin-xing LIN; Yu-dong JIA; Cai-qiao ZHANG

    2011-01-01

    The development of ovarian follicular cells is controlled by multiple circulating and local hormones and factors,including follicle-stimulating hormone (FSH) and epidermal growth factor (EGF).In this study,the stagespecific effect of EGF on FSH-induced proliferation of granulosa cells was evaluated in the ovarian follicles of egg-laying chickens.Results showed that EGF and its receptor (EGFR) mRNAs displayed a high expression in granulosa cells from the prehierarchical follicles,including the large white follicle (LWF) and small yellow follicle (SYF),and thereafter the expression decreased markedly to the stage of the largest preovulatory follicle.SYF represents a turning point of EGF/EGFR mRNA expression during follicle selection.Subsequently the granulosa cells from SYF were cultured to reveal the mediation of EGF in FSH action.Cell proliferation was remarkably increased by treatment with either EGF or FSH (0.1-100 ng/ml).This result was confirmed by elevated proliferating cell nuclear antigen (PCNA) expression and decreased cell apoptosis.Furthermore,EGF-induced cell proliferation was accompanied by increased mRNA expressions of EGFR,FSH receptor,and the cell cycle-regulating genes (cyclins D1 and E1,cyclin-dependent kinases 2 and 6) as well as decreased expression of luteinizing hormone receptor mRNA.However,the EGF or FSH-elicited effect was reversed by simultaneous treatment with an EGFR inhibitor AG1478.In conclusion,EGF and EGFR expressions manifested stage-specific changes during follicular development and EGF mediated FSH-induced cell proliferation and retarded cell differentiation in the prehierarchical follicles.These expressions thus stimulated follicular growth before selection in the egg-laying chicken.

  18. Expression of AMH in ovarian granulosa cell tumor as well as the analysis and appreciation of its histological classification%卵巢颗粒细胞瘤中AMH的表达及其组织学分级标准的分析评价

    Institute of Scientific and Technical Information of China (English)

    梁晓艳; 姚汉武; 马晓宇

    2010-01-01

    目的:检测卵巢颗粒细胞瘤(granulosa cell tumor,GCT)组织中抗苗勒管激素(anti-mullerian hormone,AMH)的表达,并用它的表达水平及相关的统计学方法对卵巢GCT的组织学分级标准进行分析评价.方法:用免疫组织化学方法探讨AMH在40例卵巢GCT组织中的表达.结果:AMH在临床Ⅲ期病例中的阳性表达率明显低于其在临床Ⅰ期和Ⅱ期中的阳性表达率(P0.05).李瑛氏组织学分级标准与临床分期有正相关关系(r=0.632,P0.05).结论:李瑛氏组织学分级标准可用于病理学对卵巢GCT的预后评估.

  19. Application of ovarian transposition during hysterectomy

    Institute of Scientific and Technical Information of China (English)

    郭毅; 沈文静; 姜艳明; 刘伟; 李秀芬

    2003-01-01

    Objective To study the optimal position and method for ovarian transposition and its benefits and indications.Methods We performed ovarian transposition in 34 patients from August 1989 to December 2000. Twelve patients were diagnosed with stage Ⅰb to Ⅱa cervical cancer, 4 had stage Ⅰa endometrial carcinoma, 12 had stage Ⅲ to Ⅳ endometriosis, 4 had myoma of uterus, 1 had dysfunctional uterine bleeding, and 1 had an ovarian granulosa cell tumor. Surgery went as follows: the ovary was dissociated by clamp, the skin was incised and a tunnel was made, then the ovary was translocated to the subcutaneous site. In the cases of benign lesions, the ovarian vessel pedicel went in through the abdominal cavity, but in malignant tumors, it went out through the peritoneum. Results In both cases (benign lesions or malignant tumors), the short-term and long-term endocrine function of the translocated ovary remained normal. Furthermore, patients could supervise their translocated ovary themselves.Conclusions Subcutaneous ovary transposition might prevent not only implantation of gastrointestinal cancer but also the extension of pelvic carcinoma to the ovary. Because of the shallow transposition and the incision scar, it is easy for patients to supervise themselves. Moreover, the site of the ovary is easy to locate for ultrasound examinations. Thus, it can obtain the goal of early prevention for cancer. Subcutaneous ovarian transposition with skin incision is the optimal selection and suitable for all patients with various gynecologic diseases in which ovary removal is not necessary.

  20. VISFATIN (NAMPT) Improves In Vitro IGF1-Induced Steroidogenesis and IGF1 Receptor Signaling Through SIRT1 in Bovine Granulosa Cells.

    Science.gov (United States)

    Reverchon, Maxime; Rame, Christelle; Bunel, Audrey; Chen, Wenyong; Froment, Pascal; Dupont, Joëlle

    2016-03-01

    VISFATIN is a novel adipokine, also known as a nicotinamide phosphorybosyltransferase (NAMPT), that is able to modulate different processes, including lipid and glucose metabolism, oxidative stress, inflammation, and insulin resistance. Recent data suggest that it also plays a role in reproductive function in rats, humans, and chickens. Here we identified VISFATIN in the bovine ovary and investigated the in vitro effects of this hormone on granulosa cell steroidogenesis and proliferation and oocyte maturation. By RT-PCR, immunoblotting, and immunohistochemistry, we found VISFATIN in various ovarian cells, including granulosa and theca cells, corpus luteum, and oocytes. In cultured bovine granulosa cells, we showed that IGF1 (10(-8) M) and VISFATIN (10 and 100 ng/ml) but not FSH (10(-8) M) increased mRNA expression levels of NAMPT after 48 h of stimulation. Moreover, we observed that human recombinant VISFATIN (hVisf, 10 ng/ml, 48 h) increased the release of progesterone and estradiol secretion, and this was associated with an increase in the protein level of STAR, the HSD3B activity, and the phosphorylation levels of IGF1R and MAPK ERK1/2 in the presence or absence of IGF1 (10(-8) M). All these effects were abolished when NAMPT was knocked down and when the sirtuin pharmacological inhibitors CHIC-35 (60 nM) and EX-527 (0.5 μM) were preincubated in bovine granulosa cells. Thus, in cultured bovine granulosa cells, VISFATIN improves basal and IGF1-induced steroidogenesis and IGF1 receptor signaling through SIRT1. PMID:26792944

  1. Expression of progesterone receptor membrane component-2 within the immature rat ovary and its role in regulating mitosis and apoptosis of spontaneously immortalized granulosa cells.

    Science.gov (United States)

    Griffin, Daniel; Liu, Xiufang; Pru, Cindy; Pru, James K; Peluso, John J

    2014-08-01

    Progesterone receptor membrane component 2 (Pgrmc2) mRNA was detected in the immature rat ovary. By 48 h after eCG, Pgrmc2 mRNA levels decreased by 40% and were maintained at 48 h post-hCG. Immunohistochemical studies detected PGRMC2 in oocytes and ovarian surface epithelial, interstitial, thecal, granulosa, and luteal cells. PGRMC2 was also present in spontaneously immortalized granulosa cells, localizing to the cytoplasm of interphase cells and apparently to the mitotic spindle of cells in metaphase. Interestingly, PGRMC2 levels appeared to decrease during the G1 stage of the cell cycle. Moreover, overexpression of PGRMC2 suppressed entry into the cell cycle, possibly by binding the p58 form of cyclin dependent kinase 11b. Conversely, Pgrmc2 small interfering RNA (siRNA) treatment increased the percentage of cells in G1 and M stage but did not increase the number of cells, which was likely due to an increase in apoptosis. Depleting PGRMC2 did not inhibit cellular (3)H-progesterone binding, but attenuated the ability of progesterone to suppress mitosis and apoptosis. Taken together these studies suggest that PGRMC2 affects granulosa cell mitosis by acting at two specific stages of the cell cycle. First, PGRMC2 regulates the progression from the G0 into the G1 stage of the cell cycle. Second, PGRMC2 appears to localize to the mitotic spindle, where it likely promotes the final stages of mitosis. Finally, siRNA knockdown studies indicate that PGRMC2 is required for progesterone to slow the rate of granulosa cell mitosis and apoptosis. These findings support a role for PGRMC2 in ovarian follicle development.

  2. Developmental programming: Prenatal BPA treatment disrupts timing of LH surge and ovarian follicular wave dynamics in adult sheep

    Science.gov (United States)

    Veiga-Lopez, A; Beckett, EM; Abi Salloum, B; Ye, W; Padmanabhan, V

    2014-01-01

    Developmental exposure to BPA adversely affects reproductive function. In sheep, prenatal BPA treatment induces reproductive neuroendocrine defects, manifested as LH excess and dampened LH surge and perturbs early ovarian gene expression. In this study we hypothesized that prenatal BPA treatment will also disrupt ovarian follicular dynamics. Pregnant sheep were treated from days 30 to 90 of gestation with 3 different BPA doses (0.05, 0.5, or 5 mg/kg BW/day). All female offspring were estrus synchronized and transrectal ultrasonography was performed daily for 22 days to monitor ovarian follicular and corpora lutea dynamics. Blood samples were collected to assess hormonal preovulatory changes and luteal progesterone dynamics. Statistical analysis revealed that the time interval between the estradiol rise and the preovulatory LH surge was shortened in the BPA-treated females. None of the three BPA doses had an effect on corpora lutea, progestogenic cycles, and mean or duration of ovulatory and non-ovulatory follicles. However, differences in follicular count trajectories were evident in all three follicular size classes (2–3 mm, 4–5 mm, and ≥ 6 mm) of prenatal BPA-treated animals compared to controls. Number of follicular waves tended also to be more variable in the prenatal BPA-treated groups ranging from 2 to 5 follicular waves per cycle, while this was restricted to 3 to 4 waves in control females. These changes in ovarian follicular dynamics coupled with defects in time interval between estradiol rise and preovulatory LH release are likely to lead to subfertility in prenatal BPA-treated females. PMID:24923655

  3. Developmental programming: Prenatal BPA treatment disrupts timing of LH surge and ovarian follicular wave dynamics in adult sheep

    Energy Technology Data Exchange (ETDEWEB)

    Veiga-Lopez, A.; Beckett, E.M.; Abi Salloum, B. [Department of Pediatrics, University of Michigan, Ann Arbor, MI (United States); Ye, W. [Department of Biostatistics, University of Michigan, Ann Arbor, MI (United States); Padmanabhan, V., E-mail: vasantha@umich.edu [Department of Pediatrics, University of Michigan, Ann Arbor, MI (United States); The Reproductive Sciences Program, University of Michigan, Ann Arbor, MI (United States)

    2014-09-01

    Developmental exposure to BPA adversely affects reproductive function. In sheep, prenatal BPA treatment induces reproductive neuroendocrine defects, manifested as LH excess and dampened LH surge and perturbs early ovarian gene expression. In this study we hypothesized that prenatal BPA treatment will also disrupt ovarian follicular dynamics. Pregnant sheep were treated from days 30 to 90 of gestation with 3 different BPA doses (0.05, 0.5, or 5 mg/kg BW/day). All female offspring were estrus synchronized and transrectal ultrasonography was performed daily for 22 days to monitor ovarian follicular and corpora lutea dynamics. Blood samples were collected to assess preovulatory hormonal changes and luteal progesterone dynamics. Statistical analysis revealed that the time interval between the estradiol rise and the preovulatory LH surge was shortened in the BPA-treated females. None of the three BPA doses had an effect on corpora lutea, progestogenic cycles, and mean number or duration of ovulatory and non-ovulatory follicles. However, differences in follicular count trajectories were evident in all three follicular size classes (2–3 mm, 4–5 mm, and ≥ 6 mm) of prenatal BPA-treated animals compared to controls. Number of follicular waves tended also to be more variable in the prenatal BPA-treated groups ranging from 2 to 5 follicular waves per cycle, while this was restricted to 3 to 4 waves in control females. These changes in ovarian follicular dynamics coupled with defects in time interval between estradiol rise and preovulatory LH release are likely to lead to subfertility in prenatal BPA-treated females. - Highlights: • Prenatal BPA shortens interval between estradiol rise and preovulatory LH surge. • Prenatal BPA affects follicular count trajectory and follicular wave occurrence. • Prenatal BPA does not affect ovulatory rate and progesterone dynamics.

  4. Gonadotropin treatment augments postnatal oogenesis and primordial follicle assembly in adult mouse ovaries?

    OpenAIRE

    Bhartiya, Deepa; Sriraman, Kalpana; Gunjal, Pranesh; Modak, Harshada

    2012-01-01

    Background Follicle stimulating hormone (FSH) exerts action on both germline and somatic compartment in both ovary and testis although FSH receptors (FSHR) are localized only on the somatic cells namely granulosa cells of growing follicles and Sertoli cells in the seminiferous tubules. High levels of FSH in females are associated with poor ovarian reserve, ovarian hyper stimulation syndrome etc. and at the same time FSH acts as a survival factor during in vitro organotypic culture of ovarian ...

  5. 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin induces oxidative stress and apoptosis of ovarian granulosa cells in rats in vitro%2,3,7,8-四氯二苯并对二噁英诱导原代培养大鼠卵巢颗粒细胞的氧化应激和凋亡

    Institute of Scientific and Technical Information of China (English)

    许虹; 许振成; 张素坤; 全松; 邢福祺

    2011-01-01

    目的 探讨2,3,7,8-四氯二苯并对二噁英(2,3,7,8-Tetrachlorodibenzo-P-dioxin,TCDD)对体外原代培养大鼠卵巢颗粒细胞的氧化损伤和促进凋亡作用,探究氧化膻激介导TCDD诱导卵巢颗粒细胞凋亡的机制,为临床防治提供基础应用性依据.方法 体外原代培养末成熟大鼠卵巢颗粒细胞,0.1、1、10和100 nmol/L TCDD染毒24 h后采用AnnexinV-FITC/PI双染流式检测细胞凋亡率;检测10nmol/L TCDD染毒0.5、1、5和24 h后细胞内活性氧(reactive oxygenspecies,ROS)、丙二醛(Malondialdehyde,MDA)、谷胱甘肽(Glutathione,GSH)水平;并添加超氧化岐化酶(Superoxidedismutase,SOD)联合处理,检测10 nmoVLTCDD联合不同剂量SOD处理后的ROS水平和100 IU/ml SOD联合处理1、3、6、18和24 h的细胞凋亡率.结果 大鼠卵巢颗粒细胞暴露于1 nmol/L TCDD 24h早期凋亡发生显著增加,10、100 nmol/L染毒24h诱导晚期凋亡和细胞死亡增加明显,与对照组差异有统计学意义(P<0.05).10 nmol/L TCDD处理不同时间均诱导颗粒细胞ROS生成、MDA增加和CSH损耗,与对照组比较差异有统计学意义(P<0.05),具有剂量依赖关系.SOD联合处理明显抑制TCDD诱导卵巢颗粒细胞的氧化应激作用和凋亡的发生.结论 TCDD诱导大鼠卵巢颗粒细胞的氧化损伤和细胞凋亡作用明显,氧化应激途径足TCDD诱导卵巢颗粒细胞凋亡的早期机制,是TCDD介导的生殖毒性机制之一.%Objective To investigate whether 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD) induces oxidative stress and apoptosis in rat granulosa cells( GCs), and to further evaluate whether TCDD is capable of inducing apoptosis in this cell type. Methods GCs were obtained from preovulatory follicles in immature rats and cultured in Vitro. AnnexinV-FITC/PI was used to determine the percentage of apoptosis of granulosa cells following the exposure to 0.1% DMSO, 0.1, 1, 10, 100nmol/L TCDD for 24 h, as well as 10nmol/L TCDD co-treated with 100 IU

  6. The diverse mechanism of action of dichlorodiphenyldichloroethylene (DDE) and methoxychlor in ovarian cells in vitro.

    Science.gov (United States)

    Chedrese, P J; Feyles, F

    2001-01-01

    Dichlorodiphenyldichloroethylene (DDE), the most stable metabolite of the organochlorine insecticide dichlorodiphenyltrichloroethane (DDT), and the DDT analog methoxychlor can have adverse effects on reproduction. These chemicals have been identified as having estrogenic activity. The aim of the current study was to examine the effects of dichlorodiphenyldichloroethylene (DDE), methoxychlor, and estradiol-17 beta on steroidogenesis and FSH responsiveness in ovarian cells in vitro. Experiments were performed on a primary culture of porcine granulosa cells and a culture of Chinese hamster ovary (CHO) cells, the latter stably transfected with the FSH receptor (CHO-FSH-R). DDE (10 microM) and estradiol-17 beta (0.1 microM) but not methoxychlor (10 microM), increased proliferation of the granulosa cells. DDE (100 and 10 microM, respectively) decreased FSH-stimulated cAMP synthesis in the granulosa and CHO-FSH-R cells. DDE also decreased progesterone synthesis in the granulosa cells. Methoxychlor (10 microM) inhibited progesterone synthesis in the granulosa cells, but it did not affect the generation of cAMP in either type of cells studied. However, methoxychlor inhibited estradiol-17 beta-stimulated progesterone synthesis in the granulosa cells. We conclude that DDE primarily inhibited the generation of cAMP, while methoxychlor suppressed progesterone synthesis through a mechanism distal to cAMP generation. The present results indicate that DDE and methoxychlor are not limited to a mimicking of the endocrine effects of estradiol-17 beta in cultured ovarian cells. Therefore, a non-estrogenic component of the endocrine disrupting activities of DDE and methoxychlor must be considered in evaluating their reproductive toxicity.

  7. Two cases report of a malignant germ cell tumour of ovary and a granulosa cell tumour:Interest of tumoral immunochemistry in the identification and management.

    OpenAIRE

    Jean eBouquet De Jolinière

    2014-01-01

    Abstract Objective: In this article, we present two case reports. The first case was a malignant germ cell tumor of the right ovary in a 23 year old female and a case of a bilateral undifferentiated granulosa cell tumor in a 71 year old female. The aim of these reports is to illustrate the interest of the immuno-histochemical analysis to define the correct diagnosis, to better classify these ovarian tumours and improve their management. Methods: This study we report two cases. The first case...

  8. Two Case Reports of a Malignant Germ Cell Tumor of Ovary and a Granulosa Cell Tumor: Interest of Tumoral Immunochemistry in the Identification and Management

    OpenAIRE

    Bouquet de Jolinière, J.; Ben Ali, N.; Fadhlaoui, A.; Dubuisson, J B; Guillou, L.; Sutter, A.; Betticher, D; Hoogewoud, H. M.; Feki, A.

    2014-01-01

    Objective: In this article, we present two case reports. The first case was a malignant germ cell tumor of the right ovary in a 23-year old woman and the second case was a bilateral undifferentiated granulosa cell tumor in a 71-year old woman. The aim of these reports is to illustrate the interest of the immunohistochemical analysis to define the correct diagnosis, to better classify these ovarian tumors and improve their management. Methods: In this study, we report two cases. The first c...

  9. Identification of calcitonin expression in the chicken ovary: influence of follicular maturation and ovarian steroids.

    Science.gov (United States)

    Krzysik-Walker, Susan M; Ocón-Grove, Olga M; Maddineni, Sreenivasa B; Hendricks, Gilbert L; Ramachandran, Ramesh

    2007-10-01

    Calcitonin (CALCA), a hormone primarily known for its role in calcium homeostasis, has recently been linked to reproduction, specifically as a marker for embryo implantation in the uterus. Although CALCA expression has been documented in several tissues, there has been no report of production of CALCA in the ovary of any vertebrate species. We hypothesized that the Calca gene is expressed in the chicken ovary, and its expression will be altered by follicular maturation or gonadal steroid administration. Using RT-PCR, we detected Calca mRNA and the calcitonin receptor (Calcr) mRNA in the granulosa and theca layers of preovulatory and prehierarchial follicles. Both CALCA and Calca mRNA were localized in granulosa and thecal cells by confocal microscopy. Using quantitative PCR analysis, F1 follicle granulosa layer was found to contain significantly greater Calca mRNA and Calcr mRNA levels compared with those of any other preovulatory or prehierarchial follicle. The granulosa layer contained relatively greater Calca and Calcr mRNA levels compared with the thecal layer in both prehierarchial and preovulatory follicles. Progesterone (P(4)) treatment of sexually immature chickens resulted in a significantly greater abundance of ovarian Calca mRNA, whereas estradiol (E(2)) or P(4) + E(2) treatment significantly reduced ovarian Calca mRNA quantity. Treatment of prehierarchial follicular granulosa cells in vitro with CALCA significantly decreased FSH-stimulated cellular viability. Collectively, our results indicate that follicular maturation and gonadal steroids influence Calca and Calcr gene expression in the chicken ovary. We conclude that ovarian CALCA is possibly involved in regulating follicular maturation in the chicken ovary. PMID:17582014

  10. ROLE OF IMMUNOHISTOCHEMISTRY IN OVARIAN TUMORS

    Directory of Open Access Journals (Sweden)

    Lubna

    2014-03-01

    Full Text Available BACKGROUND: Ovarian tumors are characterized by marked heterogeneity in their clinical presentation, so an accurate histopathological diagnosis is needed. Immunohistochemistry is helpful in vast number of cases where the morphology and clinical data alone do not allow definite diagnosis of tumor present in tissue sections. AIMS: 1. To evaluate the role of immune- histochemistry in classification and histogenesis of ovarian tumours and in resolving diagnostic dilemma in closely mimicking and poorly differentiated tumours. 2. To evaluate the role of immunohistochemistry in ovarian tumours and to differentiate primary from metastatic tumours. MATERIALS AND METHODS: 80 operated cases of ovarian tumours over a period of one and half year (January 2008 to September 2010 were studied. Paraffin blocks of various ovarian tumours for relevant immunostains were subjected for automated immunostaining. Total 52 immunostains were included in the study. RESULTS: Out of the 80 cases of ovarian tumours, benign ovarian lesions were more common (75% than malignant lesions (25%. Serous cystadenoma was the commonest benign tumor (45%. Overall surface epithelial carcinomas were responsible for 70% of all malignant lesions among which serous cyst adenocarcinoma was most common (45%. 88.8% cases of serous carcinomas showed diffuse positivity for CK7, 60% showed positivity for CA125 and 100% were negative for CK20. 100% cases of mucinous carcinoma showed positivity for CK7, 66.66% showed positivity for CEA and 100% were negative for CA125. ER and PR showed nuclear positivity in both cases (100% of endometrioid carcinoma. Dysgerminoma showed positivity for placental alkaline phosphatase (PLAP. Yolk sac tumor was positive for alpha-feto protein (AFP. Embryonal carcinoma was positive for CD30. Granulosa cell tumor was positive for Calretinin and Inhibin and negative for AFP. CONCLUSION: Thus IHC is helpful in confirming the histological diagnosis, to know the histogenesis

  11. Mechanisms of chemotherapy-induced human ovarian aging: double strand DNA breaks and microvascular compromise

    OpenAIRE

    Soleimani, Reza; Heytens, Elke; Darzynkiewicz, Zbigniew; Oktay, Kutluk

    2011-01-01

    The mechanism of chemotherapy-induced acceleration of ovarian aging is not fully understood. We used doxorubicin, a widely used cancer chemotherapeutic, in a variety of in vivo xenograft, and in vitro models to investigate the impact of chemotherapy-induced aging on the human ovary. Doxorubicin caused massive double-strand-DNA-breaks in primordial follicles, oocytes, and granulosa cells in a dose dependent fashion as revealed by accumulating γH2AX foci. This damage was associated with apoptot...

  12. Phenotypes of the ovarian follicular basal lamina predict developmental competence of oocytes

    OpenAIRE

    Irving-Rodgers, Helen F.; Morris, Stephanie; Collett, Rachael A.; Peura, Teija T.; Davy, Margaret; Jeremy G. Thompson; Mason, Helen D; Rodgers, Raymond J.

    2008-01-01

    BACKGROUND The ovarian follicular basal lamina underlies the epithelial membrana granulosa and maintains the avascular intra-follicular compartment. Additional layers of basal lamina occur in a number of pathologies, including pili annulati and diabetes. We previously found additional layers of follicular basal lamina in a significant percentage of healthy bovine follicles. We wished to determine if this phenomenon existed in humans, and if it was related to oocyte function in the bovine. MET...

  13. Tumores das células da granulosa dos ovários: estudo de 24 casos Granulosa cell tumors of the ovary: a study of 24 cases

    Directory of Open Access Journals (Sweden)

    Artur Lício Rocha Bezerra

    2004-09-01

    Full Text Available OBJETIVOS: avaliar estadiamento, procedimentos cirúrgicos e evolução dos tumores das células da granulosa (TCG dos ovários, dando ênfase à possibilidade de cirurgia conservadora (ooforectomia unilateral. MÉTODOS: este é um estudo de coorte retrospectivo no qual foram incluídas 24 pacientes com TCG tratadas no período de janeiro de 1994 a janeiro de 2004. Foram analisadas variáveis de interesse, tais como idade da paciente, sintomatologia, tamanho tumoral ao exame físico, estadiamento, modalidades de tratamento (tipos de cirurgia e adjuvância com quimioterapia e/ou radioterapia e prognóstico. As associações entre as variáveis foram avaliadas pelo teste do chi-quadrado e para significância estatística considerou-se p OBJECTIVE: to evaluate staging, surgical procedures and outcome of ovarian granulosa cell tumors (GCT, with emphasis in the possibility of conservative surgery (unilateral ooforectomy. METHODS: this is a retrospective cohort study in which 24 patients treated with GCT during the period of January 1994 to January 2004 were included. Variables of interest such as patient's age, symptoms, tumor size on physical examination, staging, treatment modalities (types of surgery and of adjuvant chemotherapy and/or radiotherapy and prognosis have been analyzed. The chi-square test was used to check the association between variables, and the level of significance was set at p < 0.05, always describing the two-tailed Fisher exact test. RESULTS: the patients' age varied from 30 to 82 (mean 51.7 years old. The most frequently referred symptom was pelvic pain (n = 10; 41.7%. Fourteen patients (58.3% presented clinical stage (CS Ic, 5 (20.8% CS IIIc and 5 (20.8% CS Ia. More advanced clinical stages were significantly associated with palpable pelvic masses (p < 0.04. Endometrial hyperplasias were found in 3 (25% of the 12 hysterectomy specimens. The follow-up period varied from 2 to 114 (mean 42.5 months. Among the 16 (66

  14. Rare non-epithelial ovarian neoplasms: Pathology, genetics and treatment.

    Science.gov (United States)

    Foulkes, William D; Gore, Martin; McCluggage, W Glenn

    2016-07-01

    Rare non-epithelial ovarian neoplasms have posed management challenges for many years. Their rarity means that most specialist practitioners will see one such case every several years, and most generalists may never see a case. The first step in management is to establish the correct diagnosis and this may necessitate specialist pathology review. Here, we review recent developments in the pathology, genetics and treatment of small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) and sex cord-stromal tumours. Pathologically, these tumours often display morphological overlap with other neoplasms; for example, SCCOHT overlaps with many other "small round blue cell" tumours. Specific immunohistochemical stains, while useful, may not always be definitive. The discovery of somatic mutations in FOXL2 (adult granulosa cell tumours) and germline and somatic mutations in DICER1 (Sertoli-Leydig cell tumours) and SMARCA4 (SCCOHT) has demonstrated the value of molecular investigation as an adjunct to traditional histopathological approaches. In addition, the presence of germline mutations in a significant proportion of some of these neoplasms points to the need for genetic counselling and testing, offering the prospect of prevention and early diagnosis. Treatment of these rare tumours, as a group, should be on the basis of sound oncological principles, given that level 1 evidence will almost always be lacking. The rationale for experimental therapies must be clearly established. In view of the complex issues involved in the management of these conditions, expert opinion in pathology, genetics and treatment may be essential to offer the patient and her family the best chance of a good outcome. PMID:27079213

  15. Paraoxonase (PON) 1, 2 and 3 expression in granulosa cells and PON1 activity in follicular fluid of dairy cows.

    Science.gov (United States)

    Schneider, A; Absalon-Medina, V A; Esposito, G; Corrêa, M N; Butler, W R

    2013-12-01

    Normal metabolic activity in ovarian follicles may result in oxidative stress and damage to oocytes. The aim of this study was to evaluate expression of the natural anti-oxidants paraoxonase (PON) 1, 2 and 3 in granulosa cells and PON1 activity in follicular fluid (FF) and plasma of dairy cows. For the first experiment, ovaries were collected from cows at slaughter, after which follicles were dissected and classified as oestrogen active (EAF) or atretic (ATF). Expression of PON1, PON2 and PON3 mRNA was evaluated in granulosa cells, and activity of PON1 was measured in FF. PON1 mRNA was undetectable in granulosa cells, PON2 mRNA expression was not different between follicle types, and PON3 mRNA tended to be higher in EAF (p = 0.11). The activity of PON1 in FF was higher (p = 0.01) for EAF (82.6 ± 8.0 kU/L) than ATF (53.9 ± 6.8 kU/L), as were high-density lipoproteins (HDL), low-density lipoproteins (LDL) and total cholesterol concentrations. In the second experiment, we aimed to compare plasma and FF PON1 activity in early lactation Holstein cows (n = 15) with pre-ovulatory EAF. Activity of PON1 was twofold higher (p < 0.0001) in plasma (122.5 ± 11.1 kU/L) than in FF (61.4 ± 5.2 kU/L). Plasma concentrations were also higher (p < 0.0001) for HDL, LDL and total cholesterol when compared to FF. In conclusion, FF concentrations of PON1, HDL, LDL and total cholesterol were higher in healthy oestrogen active bovine follicles than in atretic follicles. PON1 was not expressed by granulosa cells indicating that high PON1 activity in bovine FF is apparently derived by transfer from blood in association with HDL.

  16. Galiposin: a new beta-hydroxychalcone from Galipea granulosa.

    Science.gov (United States)

    López, J A; Barillas, W; Gomez-Laurito, J; Martin, G E; Lin, F T; Al-Rehaily, A J; Zemaitis, M A; Schiff, P L

    1998-02-01

    A novel beta-hydroxychalcone, galiposin, was isolated from the bark of Galipea granulosa. The structure of galiposin was established via spectroscopic analysis, including high resolution one- and two-dimensional nuclear magnetic resonance spectrometry, as well as mass spectroscopy. PMID:17253223

  17. Increased iNOS gene expression in the granulosa layer of F1 follicle of over-fed and under-fed broiler breeder hens

    Directory of Open Access Journals (Sweden)

    A Sheikh Ahmadi

    2010-12-01

    Full Text Available To clarify the effects of high (20 and 40% more than normal and low (20% less than normal daily feed allowance on egg and body parameters, ovarian morphology and plasma glucose, cholesterol, triacylglycerol, leptin-like hormone, nitrite/nitrate and gene expression of inducible nitric oxide synthase (iNOS in the granulosa layer of F1 follicle, broiler breeder hens (30-week-old were fed for 30 days. Egg and body parameters significantly changed between treatments (p<0.05. Effect of different level of feed intake on ovarian morphology parameters was significant (p<0.05, except for white follicles. After 30 days of experiment, plasma nitrite/nitrate (as a index of plasma nitric oxide and leptin-like hormone increased in FI+20% and FI+40% groups as compared to controls (p<0.05. Plasma level of leptin-like hormone also significantly (p<0.05 increased in FI+40% group. The relative amount of iNOS mRNA expression in the granulosa layer of F1 follicles was significantly higher in FI-20% and FI+40% groups than in control group only after 4 weeks of experiment. The amount of these elevations in the FI-20% and FI+40% groups were 32.4% and 60.9% respectively. It was concluded that iNOS gene is normally expressed in follicular granulosa cells of F1 follicle of broiler breeder hens 2-4 hours before ovulation. However, over- and underfeeding of hens increased iNOS expression in F1 follicle, which may be one of the atresia-inducing factors in hierarchical follicles as shown by the significant (p<0.05 increase of shrunken follicles in the ovary of over- and under-fed broiler breeder hens after 30 days of feeding.

  18. Preservation of ovarian function by ovarian transposition performed before pelvic irradiation during childhood.

    Science.gov (United States)

    Thibaud, E; Ramirez, M; Brauner, R; Flamant, F; Zucker, J M; Fékété, C; Rappaport, R

    1992-12-01

    Ovarian transposition in adults has been shown to protect ovarian function in about 60% of cases by reducing ovarian exposure to less than 4 to 7 Gy. We therefore evaluated the effect of ovarian transposition during childhood or adolescence. Eighteen girls had ovarian transposition performed at a mean (+/- SEM) age of 9.4 +/- 1.2 years (range, 1.2 to 16 years). Twelve were prepubertal and six had menstruated at the time of ovarian transposition. The initial abnormalities were Hodgkin disease (5 cases), iliac Ewing sarcoma (3), medulloblastoma (2), ovarian seminoma (1), and vaginal or uterine tumor (7). The irradiation was external in 11 cases and local by vaginal curietherapy in 7 cases. Fifteen girls received chemotherapy. The ovarian transposition was bilateral in 15 patients and unilateral in 3 cases; in the latter the other ovary had been destroyed by the tumor or by abdominal irradiation. Ovaries were placed just below the iliac crest (15 cases) or posterolateral to the uterus (3); thus, the calculated ovarian radiation dose was up to 9.5 Gy. At the time of evaluation (8.6 +/- 0.9 years after ovarian transposition), 16 girls had menstruated and 2 remained amenorrheic because of major lesions of the vagina and uterus caused by the vaginal curietherapy. Basal plasma gonadotropin values were normal. Ovulation was documented in seven cases. Two pregnancies occurred. Complications of ovarian transposition were present in four patients: intestinal occlusion, dyspareunia, functional ovarian cysts, and pelvic adhesions with tubal obstruction. We conclude that ovarian transposition, performed before abdominopelvic irradiation during childhood, can preserve ovarian function. Longer follow-up is required to assess the risk of ovarian dystrophy because of vascular lesions or chemotherapy. PMID:1447649

  19. Somatostatin receptors in differentiated ovarian tumors

    International Nuclear Information System (INIS)

    The presence of somatostatin receptors was investigated in 57 primary human ovarian tumors using in vitro receptor autoradiography with three different somatostatin radioligands, 125I-[Tyr11]-somatostatin-14, 125I-[Leu8, D-Trp22, Tyr25]-somatostatin-28, or 125I-[Tyr3]-SMS 201-995. Three cases, all belonging to epithelial tumors, were receptor positive; specifically 1 of 42 adenocarcinomas, 1 of 3 borderline malignancies, and 1 of 2 cystadenomas. Four other epithelial tumors (3 fibroadenomas, 1 Brenner tumor), 4 sex cord-stromal tumors (2 fibrothecomas, 2 granulosa cell tumors), and 2 germ cell tumors (1 dysgerminoma, 1 teratoma) were receptor negative. In the positive cases, the somatostatin receptors were localized on epithelial cells exclusively, were of high affinity (KD = 4.6 nmol/l [nanomolar]), and specific for somatostatin analogs. These receptors bound somatostatin-14 and somatostatin-28 radioligands with a higher affinity than the octapeptide [Tyr3]-SMS 201-995. Healthy ovarian tissue had no somatostatin receptors. A subpopulation of relatively well-differentiated ovarian tumors, therefore, was identified pathobiochemically on the basis of its somatostatin receptor content. This small group of somatostatin receptor-positive tumors may be a target for in vivo diagnostic imaging with somatostatin ligands

  20. Effect of hyperandrogen on the proliferation and apoptosis of ovarian granulosa cells of pre-adolescent mouse%高雄激素对性成熟前小鼠颗粒细胞增殖和凋亡的影响

    Institute of Scientific and Technical Information of China (English)

    江帆; 李梅; 赵考考; 刁飞扬; 马翔; 崔毓桂; 刘嘉茵

    2012-01-01

    目的 观察高浓度雄激素对性成熟前小鼠卵巢颗粒细胞增殖、凋亡的影响,初步探讨其机制,为研究多囊卵巢综合征(PCOS)病理生理机制积累更多的实验资料.方法 体外培养21 d 龄小鼠卵巢颗粒 细胞,用不同浓度的睾酮(10 -5,10 -6,10 -8 mol/L)作用24、48、72 h,噻唑蓝(MTT)比色法检测细胞活力,流式 细胞术检测细胞周期和细胞凋亡,Realtime PCR 检测Caspase-3/9、Bcl-2、Bax 等凋亡因子的变化.结果 10 -5 mol/L睾酮显著增加颗粒细胞的细胞活力;10 -5 mol/L 睾酮作用48 h,细胞周期由G1 期进入S 期,细胞早期凋亡率减少1.36%,Caspase-3 活性降低,Caspase-3/9、Bcl-2、Bax mRNA 水平表达均下降.结论高浓度雄激素增加性成熟前的卵巢颗粒细胞的细胞活力,促进细胞增殖,抑制细胞凋亡,其作用可能 通过抑制线粒体通路相关的凋亡因子的表达.本研究提示,性成熟前的高雄激素作用,可能是导致青春期 PCOS发生的原因之一.%Objective To observe the effect of testosterone on the proliferation and apoptosis of ovarian granulose cells (GCs) of pre-adolescent mouse , so as to investigate the pathophysiological mechanism of adolescent polycystic ovary syndrome ( PCOS). Methods GCs from mouse pre -adolescent ovary were differently treated with testosterone at higher concentration of 10 ,10 ,10 mol/L for 24 ,48 ,72 h. Cell viability and growth rate of GCs were assayed by MTT methods. After exposure to testosterone (10 mol/L)for 48 h, cell cycle and apoptosis rate of GCs were detected by flow cytometry. Caspase-3 activity was detected by absorption spectrometry . Expressions of Caspase-3/9,Bcl-2 and Bax mRNAs in the treated GCs were determined by real-time RT-RCR. Results Cell viability of pre-adolescent mouse GCs was significantly increased in the group treated with testosterone at 10 mol/L (P < 0. 05 ). When compared with the control group , the cell cycle from G1 phase into S phase in the

  1. Two cases report of a malignant germ cell tumour of ovary and a granulosa cell tumour:Interest of tumoral immunochemistry in the identification and management.

    Directory of Open Access Journals (Sweden)

    Jean eBouquet De Jolinière

    2014-05-01

    Full Text Available Abstract Objective: In this article, we present two case reports. The first case was a malignant germ cell tumor of the right ovary in a 23 year old female and a case of a bilateral undifferentiated granulosa cell tumor in a 71 year old female. The aim of these reports is to illustrate the interest of the immuno-histochemical analysis to define the correct diagnosis, to better classify these ovarian tumours and improve their management. Methods: This study we report two cases. The first case concern a 23 years old woman (A with a mixed germ cell tumour of the right ovary (dysgerminoma (75%, yolk sac tumour (20%, and a mature teratoma (5%, and the second case (B a bilateral non differentiated and necrotic granulosa cell tumour of both ovaries concerning a 71 year old patient. The staging system used was according to both classifications, the one of International Federation of Gynaecology and Obstetrics (FIGO 1987 for ovarian cancer, and the one of TNM code 2009. Results: The immunostaining establish the malignancy and the immunochemistry contribute to confirm effectively the right diagnosis (Table 2 and 3. Conclusion: An immuno-histochemical analysis is mandatory for the choice of chemotherapy to obtain the better response of the disease and improve the survival prognosis. The efficiency of the chemotherapy authorizes a conservative surgery including a unilateral salpingo-oophorectomy preserving fertility (A. Concerning the non-dysgerminoma tumour (B, and after a surgical staging and debulking, chemotherapy was recommended. The type of tumour and its histological feature conditioned the choice of treatment. The benefit of the immunohistological analysis in this case allowed the right adjuvant treatment. Key words: germ cell tumours, dysgerminoma, teratoma, yolk sac, ovarian cell tumour, and immunohistochemistry.

  2. The expression of AMH protein between in different developmental stages of the adult mice follicle and in ovarian tissue of different ages%AMH蛋白在性成熟小鼠卵泡发育不同阶段及自然衰老过程卵巢组织中的表达变化

    Institute of Scientific and Technical Information of China (English)

    田勇; 赖志文; 石良艳; 杨书红; 罗爱月; 王世宣

    2012-01-01

    目的:通过检测抗苗勒氏管激素(AMH)蛋白在成年小鼠卵泡发育不同阶段和自然衰老过程卵巢中的表达变化,为卵泡的生长发育调控及卵巢衰老发生发展的机制研究奠定理论基础.方法:选用12,24,36,48周龄自然衰老C57 BL/6小鼠为模型.收集12周龄C57BL/6小鼠不同发育阶段的卵巢和24,36,48周龄自然衰老C57BL/6小鼠卵巢.采用免疫组织化学方法和蛋白印迹技术检测各组卵巢中AMH蛋白的表达.结果:免疫组织化学显示,AMH蛋白在始基卵泡、初级卵泡,次级卵泡、窦状卵泡的颗粒细胞中均有表达,但在黄体和闭锁卵泡的颗粒细胞中未见表达.始基卵泡颗粒细胞中AMH蛋白表达明显低于初级卵泡、次级卵泡和窦状卵泡(P<0.05);窦状卵泡颗粒细胞中AMH蛋白表达明显低于初级卵泡和次级卵泡(P<0.05);初级卵泡和次级卵泡的AMH蛋白表达未见明显差异(P>0.05).不同鼠龄的小鼠同级别卵泡颗粒细胞AMH的染色程度未见明显差异;但是24周龄以后间质中开始出现AMH蛋白表达,并且AMH的表达随鼠龄增加而上升;48周龄小鼠卵巢间质中AMH蛋白表达明显高于24周龄和36周龄(P<0.05);24周龄与36周龄比较差异无统计学意义(P>0.05).蛋白印迹技术结果显示,AMH蛋白在小鼠卵巢组织中的表达随鼠龄增加而降低,差异有统计学意义(P<0.05).结论:AMH蛋白主要表达于卵泡发育早期阶段的颗粒细胞,并且其在间质中随鼠龄增加表达增强,但是在整个卵巢组织中其表达量随鼠龄增加而降低.提示AMH可能在卵泡发育以及卵巢衰老中起重要的调控作用.%Objective:Detecting the protein expressions of Anti mullerian hormone ( AMH ) in different developmental stages of the adult mice follicles and ovarian tissue of differ-ent ages which to establish a theory foundation for the regulation of follicle development and the mechanism researching of the development of

  3. Identification and characterization of Ca2+-activated K+ channels in granulosa cells of the human ovary

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    Berg Ulrike

    2009-04-01

    Full Text Available Abstract Background Granulosa cells (GCs represent a major endocrine compartment of the ovary producing sex steroid hormones. Recently, we identified in human GCs a Ca2+-activated K+ channel (KCa of big conductance (BKCa, which is involved in steroidogenesis. This channel is activated by intraovarian signalling molecules (e.g. acetylcholine via raised intracellular Ca2+ levels. In this study, we aimed at characterizing 1. expression and functions of KCa channels (including BKCa beta-subunits, and 2. biophysical properties of BKCa channels. Methods GCs were obtained from in vitro-fertilization patients and cultured. Expression of mRNA was determined by standard RT-PCR and protein expression in human ovarian slices was detected by immunohistochemistry. Progesterone production was measured in cell culture supernatants using ELISAs. Single channels were recorded in the inside-out configuration of the patch-clamp technique. Results We identified two KCa types in human GCs, the intermediate- (IK and the small-conductance KCa (SK. Their functionality was concluded from attenuation of human chorionic gonadotropin-stimulated progesterone production by KCa blockers (TRAM-34, apamin. Functional IK channels were also demonstrated by electrophysiological recording of single KCa channels with distinctive features. Both, IK and BKCa channels were found to be simultaneously active in individual GCs. In agreement with functional data, we identified mRNAs encoding IK, SK1, SK2 and SK3 in human GCs and proteins of IK and SK2 in corresponding human ovarian cells. Molecular characterization of the BKCa channel revealed the presence of mRNAs encoding several BKCa beta-subunits (beta2, beta3, beta4 in human GCs. The multitude of beta-subunits detected might contribute to variations in Ca2+ dependence of individual BKCa channels which we observed in electrophysiological recordings. Conclusion Functional and molecular studies indicate the presence of active IK and SK

  4. 卵巢粒层细胞瘤的研究进展%Latest Research Progress of Ovary Granulosa Cell Tumors

    Institute of Scientific and Technical Information of China (English)

    游小林; 综述; 尹如铁; 审校

    2014-01-01

    Ovarian granulosa cell tumor (GCT),a group of low grade and potential recurrence functional tumor,with the adult GCT (AGCT)and juvenile GCT(JGCT).Ovarian GCT is one of the ovarial sex cord stromal tumors,accounting for 2%-5% of ovarial tumors.Etiology of GCT is still unclear.The most common symptom of GCT patients was menstrual disorder or abnormal vaginal bleeding.Surgery is the mainstay of initial management for patients with a suspected GCT.Ovarian GCT are characterized with recurrence.Stages of GCT are always indicative to be prognosis factors.Inhibin and anti-Mullerian hormone (AMH)were reported to have a certain value for diagnosis and follow-up of GCT.A single recurrent somatic mutation of forkhead transcription factor (FOXL)2 gene c.402C→G in whole transcriptome sequencing of FOXL2 gene in AGCT.While the mutation were absent in JGCT patients.To date,its biological role of this mutation is yet unclear.In summary,patients with early stage of GCT have an excellent prognosis.Recurrence of GCT is associated with a poor prognosis.For its long-term recurrence, long-term follow-up is needed.%卵巢粒层细胞瘤(GCT)是一种少见的卵巢功能性肿瘤,占卵巢肿瘤的2%~5%。卵巢 GCT按照组织病理学类型分为成年型 GCT(AGCT)及幼年型 GCT(JGCT),其病因迄今尚未阐明。其临床上最常见临床症状为雌激素刺激症状。手术是卵巢GCT的首选治疗方法。卵巢GCT具有远期复发特点,目前认为其临床分期是影响患者预后最重要的因素,抑制素(inhibin)水平、抗苗勒管激素(AMH)等可作为诊断卵巢 GCT的血清学标志物,为其复发提供一定的临床病理学诊断参考。研究发现,在 AGCT 中,翼状螺旋/叉头转录因子(FOXL)2基因中存在一个单一、复发的体细胞突变(402C→G),而在JGCT 患者中却少有该突变。FOXL2及其突变体对卵巢 GCT发展的病理生理作用,迄今尚不清楚。总之,卵巢 GCT患者的总体预后较好,

  5. Primary Ovarian Insufficiency

    Science.gov (United States)

    ... health/premature-ovarian-failure/DS00843 International Premature Ovarian Failure Association: www.ipofa.org ... to further patient education on hormone related issues. Network Sponsors The Hormone ...

  6. Adiponectin Expression in the Porcine Ovary during the Oestrous Cycle and Its Effect on Ovarian Steroidogenesis

    Directory of Open Access Journals (Sweden)

    Anna Maleszka

    2014-01-01

    Full Text Available Adiponectin is an adipose-secreted hormone that regulates energy homeostasis and is also involved in the control of the reproductive system. The goal of the present study was to investigate changes in adiponectin gene and protein expression in porcine ovarian structures during the oestrous cycle and to examine the effects of in vitro administration of adiponectin on basal and gonadotrophin- and/or insulin-induced secretion of ovarian steroid hormones. Both gene and protein expression of adiponectin were enhanced during the luteal phase of the cycle. Adiponectin affected basal secretion of progesterone by luteal cells, oestradiol by granulosa cells, and testosterone by theca interna cells. The gonadotrophin/insulin-induced release of progesterone from granulosa and theca interna cells and the release of oestradiol and androstenedione from theca cells was also modified by adiponectin. In conclusion, the presence of adiponectin mRNA and protein in the porcine ovary coupled with our previous results indicating adiponectin receptors expression suggest that adiponectin may locally affect ovarian functions. The changes in adiponectin expression throughout the oestrous cycle seem to be dependent on the hormonal status of pigs related to the stage of the oestrous cycle. The effect of adiponectin on ovarian steroidogenesis suggests that this adipokine influences reproductive functions in pigs.

  7. Global Deletion of Trp53 Reverts Ovarian Tumor Phenotype of the Germ Cell–Deficient White Spotting Variant (Wv Mice

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    Kathy Qi Cai

    2015-01-01

    We tested if additional genetic mutation(s could convert the benign ovarian epithelial tumors to malignant tumors by crossing the Wv mutant into the Trp53 knockout background. Surprisingly, we found that global deletion of Trp53 suppressed the development of ovarian tubular adenomas in Wv mice. The ovaries of Wv/Wv; Trp53 (−/− mice were covered by a single layer of surface epithelium and lacked excessive epithelial proliferation. Rather, the ovaries contained a small number of follicles. The presence of ovarian follicles and granulosa cells, as indicated by Pgc7 and inhibin-alpha expression, correlated with the absence of epithelial lesions. A reduction of Pten gene dosage, as in Wv/Wv; Pten (+/− mice, produced a similar, though less dramatic, phenotype. We conclude that deletion of Trp53 prolongs the survival of ovarian follicles in Wv mice and consequently prevents the proliferation of ovarian epithelial cells and development of ovarian tubular adenomas. The results suggest that various cell types within the ovary communicate and mutually modulate, and an intact tissue environment is required to ensure homeostasis of ovarian surface epithelial cells. Especially, the current finding emphasizes the importance of ovarian follicles in suppressing the hyperplastic growth of ovarian epithelial cells, dominating over the loss of p53.

  8. Norepinephrine stimulates progesterone production in highly estrogenic bovine granulosa cells cultured under serum-free, chemically defined conditions

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    Piccinato Carla A

    2012-11-01

    Full Text Available Abstract Background Since noradrenergic innervation was described in the ovarian follicle, the actions of the intraovarian catecholaminergic system have been the focus of a variety of studies. We aimed to determine the gonadotropin-independent effects of the catecholamine norepinephrine (NE in the steroid hormone profile of a serum-free granulosa cell (GC culture system in the context of follicular development and dominance. Methods Primary bovine GCs were cultivated in a serum-free, chemically defined culture system supplemented with 0.1% polyvinyl alcohol. The culture features were assessed by hormone measurements and ultrastructural characteristics of GCs. Results GCs produced increasing amounts of estradiol and pregnenolone for 144h and maintained ultrastructural features of healthy steroidogenic cells. Progesterone production was also detected, although it significantly increased only after 96h of culture. There was a highly significant positive correlation between estradiol and pregnenolone production in high E2-producing cultures. The effects of NE were further evaluated in a dose–response study. The highest tested concentration of NE (10 (−7 M resulted in a significant increase in progesterone production, but not in estradiol or pregnenolone production. The specificity of NE effects on progesterone productio n was further investigated by incubating GCs with propranolol (10 (−8 M, a non-selective beta-adrenergic antagonist. Conclusions The present culture system represents a robust model to study the impact of intrafollicular factors, such as catecholamines, in ovarian steroidogenesis and follicular development. The results of noradrenergic effects in the steroidogenesis of GC have implications on physiological follicular fate and on certain pathological ovarian conditions such as cyst formation and anovulation.

  9. Removal of glycosaminoglycans from bovine granulosa cells contributes to increased binding of hydrogen-3 heparin

    Energy Technology Data Exchange (ETDEWEB)

    Ax, R.L.; Stodd, C.M.; Boehm, S.K.; Bellin, M.E.

    1986-02-01

    Granulosa cells from small or large bovine follicles were pretreated with enzymes that hydrolyze various glycosaminoglycans, and binding of (/sup 3/H)-heparin to the granulosa was measured. Binding of (/sup 3/H) heparin increased significantly after enzymatic pretreatments with chondroitinase ABC and fungal hyaluronidase, and similar results were obtained with granulosa from small and large follicles. No changes in binding of (/sup 3/H) heparin were detected after hydrolyses with chondroitinase AC and heparinase in either follicle size. Heparitinase, which hydrolyzes heparan sulfate, led to a significant 50% increase in binding of (/sup 3/H) heparin to granulosa from large follicles but was without effect in small follicles. These results suggest that the lower binding of (/sup 3/H) heparin, which has been reported with follicular enlargement, may be due to heparan sulfate occupying or obstructing binding sites for heparin on granulosa from large follicles.

  10. PGRMC1 participates in late events of bovine granulosa cells mitosis and oocyte meiosis.

    Science.gov (United States)

    Terzaghi, L; Tessaro, I; Raucci, F; Merico, V; Mazzini, G; Garagna, S; Zuccotti, M; Franciosi, F; Lodde, V

    2016-08-01

    Progesterone Receptor Membrane Component 1 (PGRMC1) is expressed in both oocyte and ovarian somatic cells, where it is found in multiple cellular sub-compartments including the mitotic spindle apparatus. PGRMC1 localization in the maturing bovine oocytes mirrors its localization in mitotic cells, suggesting a possible common action in mitosis and meiosis. To test the hypothesis that altering PGRMC1 activity leads to similar defects in mitosis and meiosis, PGRMC1 function was perturbed in cultured bovine granulosa cells (bGC) and maturing oocytes and the effect on mitotic and meiotic progression assessed. RNA interference-mediated PGRMC1 silencing in bGC significantly reduced cell proliferation, with a concomitant increase in the percentage of cells arrested at G2/M phase, which is consistent with an arrested or prolonged M-phase. This observation was confirmed by time-lapse imaging that revealed defects in late karyokinesis. In agreement with a role during late mitotic events, a direct interaction between PGRMC1 and Aurora Kinase B (AURKB) was observed in the central spindle at of dividing cells. Similarly, treatment with the PGRMC1 inhibitor AG205 or PGRMC1 silencing in the oocyte impaired completion of meiosis I. Specifically the ability of the oocyte to extrude the first polar body was significantly impaired while meiotic figures aberration and chromatin scattering within the ooplasm increased. Finally, analysis of PGRMC1 and AURKB localization in AG205-treated oocytes confirmed an altered localization of both proteins when meiotic errors occur. The present findings demonstrate that PGRMC1 participates in late events of both mammalian mitosis and oocyte meiosis, consistent with PGRMC1's localization at the mid-zone and mid-body of the mitotic and meiotic spindle. PMID:27260975

  11. Imaging features of ovarian metastases from colonic adenocarcinoma in adolescents

    International Nuclear Information System (INIS)

    This paper describes the imaging features of ovarian metastases from adenocarcinoma of the colon in adolescent females. We reviewed retrospectively abdominal and pelvic computed tomographic and pelvic ultrasound examinations, histologic slices, and clinical charts of six adolescent females with ovarian metastases secondary to adenocarcinoma of the colon. One patient had ovarian metastasis at presentation and was presumed to have a primary ovarian tumor. The ovarian metastases were either solid (n = 3), complex with both solid and cystic components (n = 2), or multilocular cysts (n = 1). The ovarian lesions were large, ranging from 6 cm to 18 cm in diameter. Colorectal carcinoma in adolescent females is frequently associated with ovarian metastases. One imaging characteristic differs in adult and adolescent ovarian metastases, although they do have features in common: in adolescents, a smaller proportion of colorectal ovarian metastases are multicystic (17%) compared with the adult series (45%). These lesions are frequently large and may be complex, multicystic, or solid. Although it is a rare disease, the differential dignosis of adnexal masses in adolescent females should include ovarian metastases from adenocarcinoma of the colon. (orig.)

  12. Regulatory effect of hypoxia-inducible factor-1α on hCG-stimulated endothelin-2 expression in granulosa cells from the PMSG-treated rat ovary.

    Science.gov (United States)

    Zhang, Jisen; Zhang, Zhenghong; Wu, Yanqing; Chen, Liyun; Luo, Qianping; Chen, Jiajie; Huang, Xiaohong; Cheng, Yong; Wang, Zhengchao

    2012-01-01

    Endothelin (ET)-2 plays a crucial role in ovarian ovulation in mammals. The present study was designed to test the hypothesis that hypoxia-inducible factor (HIF)-1α-mediated transcriptional activation contributes to the increased expression of ET-2 gene in response to hCG in rat ovarian granulosa cells (GCs) during gonadotropin-induced superovulation. By real-time RT-PCR analysis, ET-2 mRNA expression was found to significantly increase in cultured ovarian GCs after treatment with hCG, or even N-carbobenzoxyl-L-leucinyl-L-leucinyl-L-norvalinal (MG-132), while this increased ET-2 mRNA expression could also be blocked by ferrous ammonium sulfate (FAS) under human chorionic gonadotropin (hCG) treatment. Further analysis also found that these changes of ET-2 mRNA were consistent with HIF-1α expression or HIF-1 activity, and HIF-1α inhibitor echinomycin inhibited ovulation in rats. Taken together, these results indicate that ET-2 is transcriptionally activated by hCG through HIF-1α-mediated mechanism in GCs. This HIF-1α-induced transcriptional activation may be one of the important mechanisms mediating the increase of ET-2 expression in GCs during the gonadotropin-induced mammalian ovulatory process in vivo.

  13. DOSE-RESPONSE OF PORCINE OVARIAN GRANULOSA CELLS TO AMYGDALIN TREATMENT COMBINED WITH DEOXYNIVALENOL

    OpenAIRE

    Marek Halenár; Marína Medveďová; Nora Maruniaková; Dagmara Packová; Adriana Kolesárová

    2014-01-01

    Amygdalin is one of many nitrilosides, which are natural cyanide-containing substances abundant in the seeds of apricots, almond, peaches, apples, and other rosaceous plants. It is a controversial anti-tumor natural product that has been used as an alternative cancer drug for many years. On the other hand, one of the most widely distributed mycotoxin contaminating food and animal feed is deoxynivalenol (DON). Deoxynivalenol has adverse effects on humans, animals, and crops that result in illn...

  14. β-catenin/Tcf-signaling appears to establish the murine ovarian surface epithelium (OSE and remains active in selected postnatal OSE cells

    Directory of Open Access Journals (Sweden)

    Usongo Macalister

    2012-06-01

    Full Text Available Abstract Background Wnts are a family of secreted signaling molecules involved in a number of developmental processes including the establishment of cell fate, polarity and proliferation. Recent studies also implicate wnts in epithelial adult stem cell maintenance, renewal and differentiation. Wnts transduce their signal through one of three signaling pathways. The best studied, the wnt/β-catenin pathway, leads to an increase in intracellular β-catenin which acts as a co-transcription factor with members of the Tcf/Lef family. A number of wnts are expressed in the ovary, specifically in the membrana granulosa and ovarian surface epithelium (OSE. We investigated the spatio-temporal pattern of β-catenin/Tcf expression in the OSE using responsive transgenic (TopGal mice. Results The generated β-galactosidase response (lacZ+ identified the cell population that overlies the medio-lateral surface of the indifferent gonad at embryonic day (E 11.5. From E12.5 onwards, lacZ expression disappeared in cells covering the testis but remained with ovary development. LacZ+ OSE cells were present throughout embryonic and postnatal ovarian development but demonstrated an age-dependent decrease to a small proportion when animals were weaned and remained at this proportion with aging. Flow cytometric (FACS and ovarian section analyses showed lacZ+ cells constitute approximately 20% of OSE in postnatal (day 1 mice which fell to 8% in 5 day-old animals while in prepubertal and adult mice this accounted for only 0.2% of OSE. Apoptosis was undetected in OSE of neonates and β-catenin/Tcf-signaling cells were proliferative in neonatal mice indicating that neither cell death nor proliferation failure was responsible for the proportion alteration. It appeared that lacZ+ cells give rise to lacZ- cells and this was confirmed in cell cultures. The DNA-binding dye DyeCycle Violet was used to set up the side population (SP assay aimed at identifying subpopulations of OSE

  15. Transplantation of ovarian granulosa‑like cells derived from human induced pluripotent stem cells for the treatment of murine premature ovarian failure.

    Science.gov (United States)

    Liu, Te; Li, Qiong; Wang, Suwei; Chen, Chuan; Zheng, Jin

    2016-06-01

    Premature ovarian failure (POF) is a common cause of female infertility, for which there are currently no ideal treatments or medications. Furthermore, apoptosis of ovarian granulosa cells (OGCs) is an important mechanism underlying the decline in ovarian reserve and function. In the present study, several cellular growth factors and hormones were used to induce the differentiation of human induced pluripotent stem cells (iPSCs) into ovarian granulosa‑like cells (OGLCs) in vitro. Immunohistochemical staining demonstrated that OGLCs derived from iPSCs strongly expressed granulosa cell markers, including anti‑Müllerian hormone, inhibin α, inhibin β and follicle‑stimulating hormone receptor, but did not express stem cell markers, including octamer‑binding transcription factor 4, SRY (sex determining region Y)-box 2, Nanog and stage-specific embryonic antigen-4 12 days post‑induction. In addition, a mouse model of POF was generated by cyclophosphamide treatment. Subsequently, iPSC‑derived OGLCs were transplanted into the POF mice (OGLCs‑iPSCs‑POF group) in vivo. Results indicated that, compared with the control group (POF mice treated with phosphate‑buffered saline), the growth state of OGLCs was markedly improved, and mature follicles could be detected in the ovarian tissue of the OGLCs‑iPSCs‑POF group. Immunohistochemical staining demonstrated that iPSC‑derived OGLCs transplanted into POF mice not only exhibited substantial growth in murine ovarian tissues, but also strongly expressed OGC markers. Furthermore, enzyme‑linked immunosorbent assays indicated that the levels of the hormone estradiol in peripheral blood samples were significantly enhanced following transplantation of iPSC‑derived OGLCs into POF mice. Furthermore, ovarian tissue weight was significantly higher in the OGLCs‑iPSCs‑POF group compared with in the control group, and the number of atretic follicles in OGLCs‑iPSCs‑POF mice was significantly reduced, as

  16. De Novo-Synthesized Retinoic Acid in Ovarian Antral Follicles Enhances FSH-Mediated Ovarian Follicular Cell Differentiation and Female Fertility.

    Science.gov (United States)

    Kawai, Tomoko; Yanaka, Noriyuki; Richards, JoAnne S; Shimada, Masayuki

    2016-05-01

    Retinoic acid (RA) is the active form of vitamin A and is synthesized from retinol by two key enzymes, alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH). As the physiological precursor of RA, retinol impacts female reproductive functions and fertility. The expression of Adh1 and Adh5 as well as Aldh1a1 and Aldh1a7 are significantly increased in the ovaries of mice treated with equine chorionic gonadotropin/FSH. The RA receptor is expressed and localized in granulosa cells and is activated by endogenous RA as indicated by LacZ expression in granulosa cells of RA-responsive transgene-LacZ transgenic mice (RA reporter mice). Coinjection of the ADH inhibitor, 4-methylpyrazole, with equine chorionic gonadotropin significantly decreases the number and developmental competence of oocytes ovulated in response to human chorionic gonadotropin/LH as compared with controls. Injections of RA completely reverse the effects of the inhibitor of ovulation and oocyte development. When mice were fed a retinol-free, vitamin A-deficient diet that significantly reduced the serum levels of retinol, the expression of the LH receptor (Lhcgr) was significantly lower in the ovaries of the vitamin A-deficient mice, and injections of human chorionic gonadotropin failed to induce genes controlling ovulation. These results indicate that ovarian de novo biosynthesis of RA is required for the follicular expression of Lhcgr in granulosa cells and their ability to respond to the ovulatory LH surge. PMID:27022678

  17. Detection, characterization, and spontaneous differentiation in vitro of very small embryonic-like putative stem cells in adult mammalian ovary.

    Science.gov (United States)

    Parte, Seema; Bhartiya, Deepa; Telang, Jyoti; Daithankar, Vinita; Salvi, Vinita; Zaveri, Kusum; Hinduja, Indira

    2011-08-01

    The present study was undertaken to detect, characterize, and study differentiation potential of stem cells in adult rabbit, sheep, monkey, and menopausal human ovarian surface epithelium (OSE). Two distinct populations of putative stem cells (PSCs) of variable size were detected in scraped OSE, one being smaller and other similar in size to the surrounding red blood cells in the scraped OSE. The smaller 1-3 μm very small embryonic-like PSCs were pluripotent in nature with nuclear Oct-4 and cell surface SSEA-4, whereas the bigger 4-7 μm cells with cytoplasmic localization of Oct-4 and minimal expression of SSEA-4 were possibly the tissue committed progenitor stem cells. Pluripotent gene transcripts of Oct-4, Oct-4A, Nanog, Sox-2, TERT, and Stat-3 in human and sheep OSE were detected by reverse transcriptase-polymerase chain reaction. The PSCs underwent spontaneous differentiation into oocyte-like structures, parthenote-like structures, embryoid body-like structures, cells with neuronal-like phenotype, and embryonic stem cell-like colonies, whereas the epithelial cells transformed into mesenchymal phenotype by epithelial-mesenchymal transition in 3 weeks of OSE culture. Germ cell markers like c-Kit, DAZL, GDF-9, VASA, and ZP4 were immuno-localized in oocyte-like structures. In conclusion, as opposed to the existing view of OSE being a bipotent source of oocytes and granulosa cells, mammalian ovaries harbor distinct very small embryonic-like PSCs and tissue committed progenitor stem cells population that have the potential to develop into oocyte-like structures in vitro, whereas mesenchymal fibroblasts appear to form supporting granulosa-like somatic cells. Research at the single-cell level, including complete gene expression profiling, is required to further confirm whether postnatal oogenesis is a conserved phenomenon in adult mammals.

  18. Ovarian tumors among Nigerian females: A private practice experience in Benin-City, Nigeria

    OpenAIRE

    Gerald Dafe Forae; Jonathan Umezulike Aligbe

    2016-01-01

    Background: Ovarian tumors ranked high among gynecological tumor globally. Reports have it that ovarian tumors cut across all age groups, but more common in adult females. Currently, ovarian cancer is the 4th most common cancer in terms of incidence and mortality patterns in women globally. To highlight the frequency and histological types of ovarian tumors in a private practice establishment in Benin-City, Southern Nigeria. Materials and Methods: Hematoxylin and eosin stained-slides of ovari...

  19. Expression of inhibin α, matrix metalloproteinase-2 and tissue inhibitors of metalloproteinase-1 in luteinized granulosa cells: comparison between women with and without endometriosis

    Institute of Scientific and Technical Information of China (English)

    Tan Rong-rong; Liu Li-peng; Pu Dan-hua; Cui Yu-gui; Jiang Shi-Wen; Liu Jia-yin; Wu Jie

    2012-01-01

    Objective: To assess the differences in expression of inhibin α,MMP-2 and TIMP-1 in luteinized granulosa cells from women with and without endometriosis undergoing in vitro fertilization (IVF),and determine whether inhibin α,MMP-2 and TIMP-1 expressions correlate with the follicle development in patients with endometriosis.Methods: Thirty six infertile patients with stage Ⅲ and Ⅳ endometriosis patients (group A) and 35 tubal infertile and/or male factor patients (group B) attending to the clinic of Jiangsu Provincial Hospital Human Reproductive Center during May 2011 and December 2011 were included in this prospective study.The patients with the number of mature oocyte ≤ 4 were considered as poor responders.According to this,the two groups were further divided into four subgroups: A1 group (23 endometriosis patients with normal response),A2 group (13 endometriosis patients with poor response),B1 group (23 controls with normal response) and B2 group (12 controls with poor response).Fasting blood samples were collected on the first day of ovarian stimulation and on the day of hCG administration,and follicle fluid were collected on the day of oocytes retrieved.The concentrations of follicle stimulating hormone (FSH),Luteinizing hormone (LH) and estradiol (E2) were measured by ECILA.Granulosa was collected from follicle fluid by Percoll method,and Stepone real-time polymerase chain reaction (PCR) was used to analysis the expression level of inhibin α,MMP-2 and TIMP-1.Results: The expression of inhibin α in endometriosis group and poor responders in control group were significantly lower than those of the normal responders in control group,in which the alternation of inhibin α expression was not correlated to the variables of follicle development.Moreover,MMP-2 levels were lower and TIMP-1 levels were higher in both endometriosis and tubal/male infertility poor responders compared to normal ovarian responders.Interestingly,the correlation between MMP-2 or

  20. Feto-maternal outcomes of pregnancy complicated by ovarian sex-cord stromal tumor: a systematic review of literature.

    Science.gov (United States)

    Blake, Erin A; Carter, Charelle M; Kashani, Banafsheh N; Kodama, Michiko; Mabuchi, Seiji; Yoshino, Kiyoshi; Matsuo, Koji

    2014-04-01

    Sex-cord stromal tumors (SCSTs) are rare ovarian cancers and their behavior during pregnancy is not well understood. To evaluate the maternal and fetal outcomes of pregnancy complicated by ovarian SCST, a systematic literature search was conducted in PubMed/MEDLINE using entry key words "pregnancy" and each type of ovarian SCST ("sex cord stromal tumor," "granulosa cell tumor," "thecoma," "Sertoli-Leydig cell tumor," or "gynandroblastoma") between 1955 and 2012 that identified 46 cases eligible for the analysis. Clinical characteristics, pregnancy outcome, tumor characteristics, and survival outcomes were evaluated. Serious adverse events were defined as complications related to the SCST that resulted in severe morbidity or mortality for mother, fetus, or both. The most common histology was granulosa cell tumor (22.0%), followed by thecoma (18.6%) and Sertoli-Leydig cell tumor (8.5%). Abdomino-pelvic pain (45.7%), palpable mass (30.4%), and virilization (26.1%) were the three most common symptoms. The majority were stage I (76.1%), tumor size stage (stages II-IV versus I, 76.1% versus 23.9%, OR 5.82, 95%CI 2.05-48.9, p=0.022) as risk factors of increased SAE. Overall survival of patients diagnosed with ovarian SCST during pregnancy was comparable to ovarian SCST not related to pregnancy (5-year rate, stages I and II-IV, 100% and 70.0%, respectively). In conclusion, although the majority of cases resulted in live birth, ovarian SCST-complicated pregnancy falls into the category of high-risk pregnancy. Risk factors for SAE identified in our study will help to guide strategic management of pregnancy complicated by ovarian SCST.

  1. Gene expression patterns in granulosa cells and oocytes at various stages of follicle development as well as in in vitro grown oocyte-and-granulosa cell complexes.

    Science.gov (United States)

    Munakata, Yasuhisa; Kawahara-Miki, Ryoka; Shiratsuki, Shogo; Tasaki, Hidetaka; Itami, Nobuhiko; Shirasuna, Koumei; Kuwayama, Takehito; Iwata, Hisataka

    2016-08-25

    Follicle development is accompanied by proliferation of granulosa cells and increasing oocyte size. To obtain high-quality oocytes in vitro, it is important to understand the processes that occur in oocytes and granulosa cells during follicle development and the differences between in vivo and in vitro follicle development. In the present study, oocytes and granulosa cells were collected from early antral follicles (EAFs, 0.5-0.7 mm in diameter), small antral follicles (SAFs, 1-3 mm in diameter), large antral follicles (LAFs, 3-7 mm in diameter), and in vitro grown oocyte-and-granulosa cell complexes (OGCs), which were cultured for 14 days after collection from EAFs. Gene expression was analyzed comprehensively using the next-generation sequencing technology. We found top upstream regulators during the in vivo follicle development and compared them with those in in vitro developed OGCs. The comparison revealed that HIF1 is among the top regulators during both in vivo and in vitro development of OGCs. In addition, we found that HIF1-mediated upregulation of glycolysis in granulosa cells is important for the growth of OGCs, but the cellular metabolism differs between in vitro and in vivo grown OGCs. Furthermore, on the basis of comparison of upstream regulators between in vivo and in vitro development of OGCs, we believe that low expression levels of FLT1 (VEGFA receptor), SPP1, and PCSK6 can be considered causal factors of the suboptimal development under in vitro culture conditions.

  2. Ultrastructure of the theca interna of ovarian follicles in sheep.

    Science.gov (United States)

    O'Shea, J D; Cran, D G; Hay, M F; Moor, R M

    1978-03-13

    The theca interna of non-atretic ovarian follicles from 2.0 mm in diameter up to the stage shortly following ovulation was studied by light and electron microscopy. In follicles less than 3.0 mm in diameter, the theca interna consisted of about 8-12 layers of flattened cells, together with many capillaries and small bundles of collagen. Two main forms of cellular differentiation were seen. These were towards either fibroblast-like cells or presumed steroidogenic cells whose cytoplasm contained large amounts of predominantly smooth tubular endoplasmic reticulum, to which some ribosomes were attached. The majority of cells were of relatively undifferentiated or intermediate structure. In larger follicles up to the early stages of oestrus the theca interna cells became larger and less flattened, and cells rich in tubular endoplasmic reticulum became proportionately more numerous. By 18 h after the onset of oestrus the theca interna was oedematous, and many cells possessed pseudopodia. Many cells also contained numerous lipid droplets, but there were no signs of thecal cell degeneration or death. Shortly after ovulation the basal lamina of the membrana granulosa was incomplete, and it became more difficult to distinguish between theca and granulosa layers. Structural heterogeneity, with two major cell types and cells of intermediate structure, was present at all stages. It was concluded that: (1) the theca interna of 2.0-2.9 mm follicles contained many cells whose structure was compatible with a steroidogenic capacity; (2) changes in the differentiated thecal cells up to the early stages of oestrus were quantitative rather than qualitative, and suggestive of an increased steroidogenic capacity; (3) the accumulation of lipid in many cells of the theca interna by 18 h after the onset of oestrus probably reflected a reduction in steroidogenic activity; and (4) there was no evidence of any structural specialization to facilitate the transport of steroids from the theca

  3. MicroRNAs and Recent Insights into Pediatric Ovarian Cancers

    Directory of Open Access Journals (Sweden)

    Jessica Anne Crawford

    2013-04-01

    Full Text Available Ovarian cancer is the most common pediatric gynecologic malignancy. When diag-nosed in children, ovarian cancers present unique challenges that differ dramatically from those faced by adults. Here, we review the spectrum of ovarian cancers found in young women and girls and discuss the biology of these diseases. A number of advances have re-cently shed significant new understanding on the potential causes of ovarian cancer in this unique population. Particular emphasis is placed on understanding how altered expression of non-coding RNA transcripts known as microRNAs play a key role in the etiology of ovarian germ cell and sex cord-stromal tumors. Emerging transgenic models for these diseases are also reviewed. Lastly, future challenges and opportunities for understanding pediatric ovarian cancers, delineating clinically useful biomarkers and developing targeted therapies are discussed.

  4. Endocrine disruptive actions of inhaled benzo(a)pyrene on ovarian function and fetal survival in fisher F-344 adult rats.

    Science.gov (United States)

    Archibong, Anthony E; Ramesh, Aramandla; Inyang, Frank; Niaz, Mohammad S; Hood, Darryl B; Kopsombut, Prapaporn

    2012-12-01

    This study evaluated the effect of inhaled BaP on female reproductive function. Rats were exposed to 50, or 75 or 100 μg BaP/m(3), 4 h a day for 14 days via inhalation. Plasma E(2), P(4), LH and FSH concentrations were determined. Ovarian BaP metabolism and aryl hydrocarbon hydrolase (AHH) activity at proestrus were determined and fertility evaluations were conducted. Ovulation rate and number of pups/litter were reduced in rats exposed to 100 μg BaP/m(3) compared with other treatment and control groups. Plasma concentrations of E(2), and LH were significantly reduced at proestrus in BaP-exposed versus those of controls whereas those of P(4) were significantly reduced at diestrus I. The activity of AHH in ovarian and liver tissues and concentrations of BaP 7,8-diol and BaP 3,6-dione metabolites increased in an exposure concentration-dependent manner. These data suggest that exposure of rats to BaP prior to mating contributes to reduced ovarian function and fetal survival. PMID:23059060

  5. The anti-epileptic drug valproic acid (VPA inhibits steroidogenesis in bovine theca and granulosa cells in vitro.

    Directory of Open Access Journals (Sweden)

    Claire Glister

    Full Text Available Valproic acid (VPA is used widely to treat epilepsy and bipolar disorder. Women undergoing VPA treatment reportedly have an increased incidence of polycystic ovarian syndrome (PCOS-like symptoms including hyperandrogenism and oligo- or amenorrhoea. To investigate potential direct effects of VPA on ovarian steroidogenesis we used primary bovine theca (TC and granulosa (GC cells maintained under conditions that preserve their 'follicular' phenotype. Effects of VPA (7.8-500 µg/ml on TC were tested with/without LH. Effects of VPA on GC were tested with/without FSH or IGF analogue. VPA reduced (P99% decrease; P<0.0001 with lesser effects on LHR, STAR, CYP11A1 and HSD3B1 mRNA (<90% decrease; P<0.05. VPA only reduced TC progesterone secretion induced by the highest (luteinizing LH dose tested; TC number was unaffected by VPA. At higher concentrations (125-500 µg/ml VPA inhibited basal, FSH- and IGF-stimulated estradiol secretion (P<0.0001 by GC without affecting progesterone secretion or cell number. VPA reversed FSH-induced upregulation of CYP19A1 and HSD17B1 mRNA abundance (P<0.001. The potent histone deacetylase (HDAC inhibitors trichostatin A and scriptaid also suppressed TC androstenedione secretion and granulosal cell oestrogen secretion suggesting that the action of VPA reflects its HDAC inhibitory properties. In conclusion, these findings refute the hypothesis that VPA has a direct stimulatory action on TC androgen output. On the contrary, VPA inhibits both LH-dependent androgen production and FSH/IGF-dependent estradiol production in this in vitro bovine model, likely by inhibition of HDAC.

  6. Sex steroids level in blood plasma and ovarian follicles of the chimeric chicken.

    Science.gov (United States)

    Sechman, A; Lakota, P; Wojtysiak, D; Hrabia, A; Mika, M; Lisowski, M; Czekalski, P; Rzasa, J; Kapkowska, E; Bednarczyk, M

    2006-12-01

    The study was performed to determine the hormonal status of mature germline chimeras obtained by blastodermal cell transfer from chicken embryos of a donor breed [Green-legged Partridgelike breed (GP) x Araucana (AR)] to those of a recipient breed [White Leghorn (WL)] being at the same stage of embryonic development. The egg-laying chimeras and WL hens (control) of the same age were used in the experiment. At first, blood samples were taken from each bird at 0.5, 5, 12.5 and 18.5 h following oviposition. Subsequently, the chimeras and the WL hens were decapitated 1-2 h after ovulation. A stroma and the following follicles were isolated from the ovary: white normal (1-4, 4-6 and 6-8 mm), white atretic and yellow preovulatory follicles (F4-F1). Sex hormones, progesterone (P4), testosterone (T) and oestradiol (E2) in blood plasma and ovarian follicles were determined radioimmunologically. The activity of the 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in the granulosa and theca layers of the follicles was analysed histochemically. In chimeric chickens, a higher level of T in blood plasma during the ovulatory cycle was noticed. However, in the stroma, white prehierarchical and medium-size preovulatory ovarian follicles the level of T was significantly lower. With respect to E2, its elevated levels were found both in blood and in the ovarian follicles. There were no significant differences in P4 concentrations in blood plasma while in ovarian follicles a higher level was observed only in white 6-8 mm follicles. 3beta-HSD activity in granulosa and theca layers of the ovarian follicles in chimeras was not different from that in the WL hens. In conclusion, the results obtained indicate that germline chimeras exhibit significant alterations in sex hormone levels in the ovary and blood plasma, which in turn may affect their reproductive abilities. PMID:17105570

  7. The Effects of Hydro-alcoholic Extract of Raspberry Fruit on Ovarian follicles and serum parameters in Poly Cystic Ovary Syndrome-Induced Rat

    Directory of Open Access Journals (Sweden)

    mohamad Nabiuni

    2015-02-01

    Full Text Available Background & aim: Polycystic Ovary Syndrome is an endocrine disorder leading to lack of ovulation and has inflammatory aspects. Raspberry extract, with possession of bioactive compounds such as Anthocyanins and polyphenols, have anti-inflammatory properties. In this study, the anti-inflammatory effects of raspberry extract on the development process of ovarian follicles and hormones level of pituitary, ovarian, and liver in rats suffering from PCOS were examined. Methods: In the present experimental study, 120 adult Wistar rats were divided into three groups of control, PCOS, and treated with raspberry. The induction of syndrome was done by 2mg Estradiol valerate. After a period of 60 days, 100, 150 and 200 mg/kg BW raspberry extract was injected intraperitoneally. Control group received no injection. Ten days after the last injection, all groups were anesthetized by chloroform and the serum and ovary of all groups were collected in order to investigate the histological and serologic changes. Data obtained were analyzed by using one-way ANOVA. Results: Raspberry-treated group showed a significant decrease in the hormones rate of testosterone, estradiol, LH, and CRP compared with PCOS (p<0.05, whereas a significant increase was observed in the serum level of Progesterone and FSH (p<0.05. A significant increase was observed in the number of corpus luteum and granulosa layer thickness in the raspberry-treated group compared with PCOS (p<0.05. Conclusion: The results demonstrated that the antioxidant and anti-inflammatory effects of raspberry extract was effective on regulating the hormones, CRPand improving of cysts which led to the initiation of ovulation.

  8. Long-Term Moderate Oxidative Stress Decreased Ovarian Reproductive Function by Reducing Follicle Quality and Progesterone Production

    Science.gov (United States)

    Lai, Zhiwen; Tian, Yong; Fang, Li; Wu, Meng; Xiong, Jiaqiang; Qin, Xian; Luo, Aiyue; Wang, Shixuan

    2016-01-01

    Ovarian aging is a long-term and complex process associated with a decrease in follicular quantity and quality. The damaging effects of reactive oxygen species (ROS) in ovarian aging and ovarian aging-associated disorders have received relatively little attention. Thus, we assessed if the oxidative stress induced by long-term (defined by the Environmental Protection Agency as at least 30 days in duration) moderate ozone inhalation reduced ovarian reserves, decreased ovarian function and induced ovarian aging-associated disorders. The expression of oxidative stress markers and antioxidant enzymes was used to determine the degree of oxidative stress. Ultrastructural changes in ovarian cells were examined via electron microscopy. The ovarian reserve was assessed by measuring multiple parameters, such as the size of the primordial follicle pool and anti-Müllerian hormone (AMH) expression. The estrous cycle, hormone levels and fertility status were investigated to assess ovarian function. To investigate ovarian aging-associated disorders, we utilized bone density and cardiovascular ultrasonography in mice. The levels of oxidized metabolites, such as 8-hydroxy-2´-deoxyguanosine (8-OHdG), 4-hydroxynonenal (4-HNE) and nitrotyrosine (NTY), significantly increased in ovarian cells in response to increased oxidative stress. The ultrastructural analysis indicated that lipid droplet formation and the proportion of mitochondria with damaged membranes in granulosa cells were markedly increased in ozone-exposed mice when compared with the control group. Ozone exposure did not change the size of the primordial follicle pool or anti-Müllerian hormone (AMH) expression. The estrogen concentration remained normal; however, progesterone and testosterone levels decreased. The mice exposed to ozone inhalation exhibited a substantial decrease in fertility and fecundity. No differences were revealed by the bone density or cardiovascular ultrasounds. These findings suggest that the

  9. Primary ovarian insufficiency

    NARCIS (Netherlands)

    De Vos, Michel; Devroey, Paul; Fauser, Bart C. J. M.

    2010-01-01

    Primary ovarian insufficiency is a subclass of ovarian dysfunction in which the cause is within the ovary. In most cases, an unknown mechanism leads to premature exhaustion of the resting pool of primordial follicles. Primary ovarian insufficiency might also result from genetic defects, chemotherapy

  10. Ovarian cancer and smoking

    DEFF Research Database (Denmark)

    Beral, V; Gaitskell, K; Hermon, C;

    2012-01-01

    Smoking has been linked to mucinous ovarian cancer, but its effects on other ovarian cancer subtypes and on overall ovarian cancer risk are unclear, and the findings from most studies with relevant data are unpublished. To assess these associations, we review the published and unpublished evidence....

  11. Fractalkine restores the decreased expression of StAR and progesterone in granulosa cells from patients with polycystic ovary syndrome

    Science.gov (United States)

    Huang, Shuo; Pang, Yanli; Yan, Jie; Lin, Shengli; Zhao, Yue; Lei, Li; Yan, Liying; Li, Rong; Ma, Caihong; Qiao, Jie

    2016-01-01

    Low progesterone levels are associated with luteal phase deficiency in women with polycystic ovary syndrome (PCOS). The mechanisms regulating progesterone biosynthesis in the granulosa cells from women with PCOS is largely unknown. Fractalkine is expressed in human ovaries, and is reported to regulate progesterone production in granulosa cells of healthy women. In the current study, we aimed to examine the role of fractalkine in women with PCOS. Reduced fractalkine levels were found in follicular fluid and granulosa cells, accompanied by decreased progesterone production and reduced steroidogenic acute regulatory protein (StAR) expression in the granulosa cells of patients with PCOS. Administration of fractalkine reversed the inhibition of progesterone and StAR expression. The mechanism mediating these effects may be associated with the inhibition of ERK activity in the granulosa cells from women with PCOS. Our findings revealed that fractalkine regulated steroidogenesis in follicular granulosa cells of women with PCOS. PMID:27386819

  12. Fractalkine restores the decreased expression of StAR and progesterone in granulosa cells from patients with polycystic ovary syndrome.

    Science.gov (United States)

    Huang, Shuo; Pang, Yanli; Yan, Jie; Lin, Shengli; Zhao, Yue; Lei, Li; Yan, Liying; Li, Rong; Ma, Caihong; Qiao, Jie

    2016-01-01

    Low progesterone levels are associated with luteal phase deficiency in women with polycystic ovary syndrome (PCOS). The mechanisms regulating progesterone biosynthesis in the granulosa cells from women with PCOS is largely unknown. Fractalkine is expressed in human ovaries, and is reported to regulate progesterone production in granulosa cells of healthy women. In the current study, we aimed to examine the role of fractalkine in women with PCOS. Reduced fractalkine levels were found in follicular fluid and granulosa cells, accompanied by decreased progesterone production and reduced steroidogenic acute regulatory protein (StAR) expression in the granulosa cells of patients with PCOS. Administration of fractalkine reversed the inhibition of progesterone and StAR expression. The mechanism mediating these effects may be associated with the inhibition of ERK activity in the granulosa cells from women with PCOS. Our findings revealed that fractalkine regulated steroidogenesis in follicular granulosa cells of women with PCOS. PMID:27386819

  13. Fractalkine restores the decreased expression of StAR and progesterone in granulosa cells from patients with polycystic ovary syndrome.

    Science.gov (United States)

    Huang, Shuo; Pang, Yanli; Yan, Jie; Lin, Shengli; Zhao, Yue; Lei, Li; Yan, Liying; Li, Rong; Ma, Caihong; Qiao, Jie

    2016-07-08

    Low progesterone levels are associated with luteal phase deficiency in women with polycystic ovary syndrome (PCOS). The mechanisms regulating progesterone biosynthesis in the granulosa cells from women with PCOS is largely unknown. Fractalkine is expressed in human ovaries, and is reported to regulate progesterone production in granulosa cells of healthy women. In the current study, we aimed to examine the role of fractalkine in women with PCOS. Reduced fractalkine levels were found in follicular fluid and granulosa cells, accompanied by decreased progesterone production and reduced steroidogenic acute regulatory protein (StAR) expression in the granulosa cells of patients with PCOS. Administration of fractalkine reversed the inhibition of progesterone and StAR expression. The mechanism mediating these effects may be associated with the inhibition of ERK activity in the granulosa cells from women with PCOS. Our findings revealed that fractalkine regulated steroidogenesis in follicular granulosa cells of women with PCOS.

  14. Morphometry in the differential diagnosis of granulosa-cell tumors of the ovary.

    Science.gov (United States)

    Sassen, R J; Baak, J P

    1986-09-01

    Although the diagnosis of granulosa-cell tumors of the ovary is usually consistent and reproducible, in some cases the differentiation from poorly differentiated adenocarcinomas can be difficult. To investigate our subjective impression of the similarity of nuclei in both types of tumors, seven granulosa-cell tumors and eight poorly differentiated adenocarcinomas were studied with morphometry, with a variety of nuclear parameters measured in 100 nuclei per case. The findings showed that, in general, granulosa-cell tumors have a slightly higher mean nuclear contour index (NCI), which is a measure of the nuclear indentation or grooving, and a somewhat lower mean nuclear area than do adenocarcinomas. There is considerable overlap, however, with the nuclear patterns of the two types of tumors forming a morphologic continuum. Multivariate analysis gave a better discrimination but did not entirely eliminate the overlap. The maximum NCI was the best single discriminator. While only one of the granulosa-cell tumors had a maximum NCI less than 5.11, none of the adenocarcinomas exceeded this value. The only granulosa-cell tumor with a maximum NCI below the threshold was in a case with a much less favorable clinical course. The results of this study indicate that objective morphometric nuclear criteria are useful in the diagnosis of granulosa-cell tumors and possibly have some prognostic value. PMID:3778617

  15. Targeting TBP-associated factors in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Jennifer R Ribeiro

    2014-03-01

    Full Text Available As ovarian tumors progress, they undergo a process of dedifferentiation, allowing adaptive changes in growth and morphology that promote metastasis and chemoresistance. Herein, we outline a hypothesis that TATA-box binding protein (TBP associated factors (TAFs, which compose the RNA Polymerase II initiation factor, TFIID, contribute to regulation of dedifferentiation states in ovarian cancer. Numerous studies demonstrate that TAFs regulate differentiation and proliferation states; their expression is typically high in pluripotent cells and reduced upon differentiation. Strikingly, TAF2 exhibits copy number increases or mRNA overexpression in 73% of high grade serous ovarian cancers (HGSC. At the biochemical level, TAF2 directs TFIID to TATA-less promoters by contact with an Initiator element, which may lead to the deregulation of the transcriptional output of these tumor cells. TAF4, which is altered in 66% of HGSC, is crucial for the stability of the TFIID complex and helps drive dedifferentiation of mouse embryonic fibroblasts to induced pluripotent stem cells. Its ovary-enriched paralog, TAF4B, is altered in 26% of HGSC. Here, we show that Taf4b mRNA correlates with Cyclin D2 mRNA expression in human granulosa cell tumors. TAF4B may also contribute to regulation of tumor microenvironment due to its estrogen-responsiveness and ability to act as a cofactor for NFκB. Conversely, TAF9, a cofactor for p53 in regulating apoptosis, may act as a tumor suppressor in ovarian cancer, since it is downregulated or deleted in 98% of HGSC. We conclude that a greater understanding of mechanisms of transcriptional regulation that execute signals from oncogenic signaling cascades is needed in order to expand our understanding of the etiology and progression of ovarian cancer, and most importantly to identify novel targets for therapeutic intervention.

  16. Cholesterol side-chain cleavage cytochrome P450 and 3beta-hydroxysteroid dehydrogenase expression and the concentrations of steroid hormones in the follicular fluids of different phenotypes of healthy and atretic bovine ovarian follicles.

    Science.gov (United States)

    Irving-Rodgers, Helen F; Krupa, Malgorzata; Rodgers, Raymond J

    2003-12-01

    Bovine ovarian antral follicles exhibit either one or the other of two patterns of granulosa cell death in atresia. Death can commence either from the antrum and progress toward the basal lamina (antral atresia) or the converse (basal atresia). In basal atresia, the remaining live antrally situated cells appeared to continue maturing. Beyond that, little is known about these distinct patterns of atresia. Healthy (nonatretic) follicles also exhibit either one or the other of two patterns of granulosa cell shape, follicular basal lamina ultrastructure or location of younger cells within the membrana granulosa. To examine these different phenotypes, the expression of the steroidogenic enzymes cholesterol side-chain cleavage cytochrome P450 (SCC) and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) in granulosa cells and concentrations of steroid hormones in follicular fluid were measured in individual histologically classified bovine antral follicles. Healthy follicles first expressed SCC and 3beta-HSD in granulosa cells only when the follicles reached an approximate threshold of 10 mm in diameter. The pattern of expression in antral atretic follicles was the same as healthy follicles. Basal atretic follicles were all basal atretic follicles were found to have substantially elevated progesterone (P basal atretic follicles. Our findings have two major implications. First, the traditional method of identifying atretic follicles by measurement of steroid hormone concentrations may be less valid with small bovine follicles. Second, features of the two forms of follicular atresia are so different as to imply different mechanisms of initiation and regulation. PMID:12930727

  17. Ovarian volume throughout life

    DEFF Research Database (Denmark)

    Kelsey, Thomas W; Dodwell, Sarah K; Wilkinson, A Graham;

    2013-01-01

    cancer. To date there is no normative model of ovarian volume throughout life. By searching the published literature for ovarian volume in healthy females, and using our own data from multiple sources (combined n=59,994) we have generated and robustly validated the first model of ovarian volume from...... to about 2.8 mL (95% CI 2.7-2.9 mL) at the menopause and smaller volumes thereafter. Our model allows us to generate normal values and ranges for ovarian volume throughout life. This is the first validated normative model of ovarian volume from conception to old age; it will be of use in the diagnosis...

  18. Stress induced alterations in pre-pubertal ovarian follicular development in rat

    Directory of Open Access Journals (Sweden)

    Yajurvedi H.N.

    2011-12-01

    Full Text Available The objective of the study was to find out whether stress experienced during neo-natal period alters the timing of formation of pre-antral and antral follicles and if so, whether pre-treatment with CRH receptor antagonist prevents these effects in rats. New born rat pups (n= 15 were exposed to maternal separation (6 hours/ day from post-natal day (PND 1 to 7 and were killed on PND 8, 11 and 15. The time of exposure was randomly changed every day during light phase (7Am to 7Pm of the day to avoid habituation. There was a significant increase in serum corticosterone levels on PND 8 and 11 in stress group rats compared to controls indicating stress response in these pups. The ovary of both control and stressed rats contained oocytes and primary follicles on PND 8 and 11 and in showed progress of follicular development upto to pre-antral and early antral follicle formation on PND 11 and 15. However, mean number of healthy oocytes and all categories of follicles at all ages studied were significantly lower in stressed rats compared to controls. Concomitant with these changes, number of atreatic follicles showed an increase over control values in stressed rats. The increase in atresia of follicles was due to apoptosis as shown by increase in the percentage of granulosa cells showing TUNEL positive staining and caspase 3 activity. On the other hand, pre-treatment with CRH- receptor antagonist (CRH 9-41 2ng/ 0.1 ml/ rat prior to undergoing stress regime on PND 1 to 7, prevented alterations in pre- pubertal follicular development thereby indicating that the ovarian changes were due to effects of stress induced activation of HPA axis. The results indicate that, stress during neonatal phase, though does not affect timing of formation of pre-antral and antral follicles, it does enhance atresia of follicles of all categories, including follicular reserve, which may affect the reproductive potential of adults. The results, for the first time reveal that CRF

  19. Paracrine effects of oocyte secreted factors and stem cell factor on porcine granulosa and theca cells in vitro

    OpenAIRE

    Webb Bob; Mitchell Marcus RP; Brankin Victoria; Hunter Morag G

    2003-01-01

    Abstract Oocyte control of granulosa and theca cell function may be mediated by several growth factors via a local feedback loop(s) between these cell types. This study examined both the role of oocyte-secreted factors on granulosa and thecal cells, cultured independently and in co-culture, and the effect of stem cell factor (SCF); a granulosa cell derived peptide that appears to have multiple roles in follicle development. Granulosa and theca cells were isolated from 2–6 mm healthy follicles...

  20. ENDOCRINE DISRUPTIVE ACTIONS OF INHALED BENZO(a)PYRENE ON OVARIAN FUNCTION AND FETAL SURVIVAL IN FISHER F-344 ADULT RATS

    OpenAIRE

    Archibong, Anthony E.; Ramesh, Aramandla; Inyang, Frank; Niaz, Mohammad S.; Hood, Darryl B.; Kopsombut, Prapaporn

    2012-01-01

    This study evaluated the effect of inhaled BaP on female reproductive function. Rats were exposed to 50, or 75 or 100 μg BaP/m3, four hours a day for 14 days via inhalation. Plasma E2, P4, LH and FSH concentrations were determined. Ovarian BaP metabolism and aryl hydrocarbon hydrolase (AHH) activity at proestrus were determined and fertility evaluations were conducted. Ovulation rate and number of pups/litter were reduced in rats exposed to 100 μg BaP/m3 compared with other treatment and cont...

  1. Laparoscopic Ovarian Surgery in Children and Adolescents

    OpenAIRE

    Kim, Hong-Bae; Cho, Hye-Yon; Park, Sung-Ho; Park, Sung-Taek

    2015-01-01

    Background and Objectives: Although laparoscopy is widely used in gynecologic surgery in adults, few studies have been undertaken to examine its use in young and adolescent patients. This study was conducted to investigate the safety and feasibility of laparoscopic surgery for the treatment of benign ovarian disease in children and adolescents. Methods: A retrospective chart review was conducted on 106 patients (age,

  2. Ovarian Cancer Stroma: Pathophysiology and the Roles in Cancer Development

    International Nuclear Information System (INIS)

    Ovarian cancer represents one of the cancers with the worst prognostic in adult women. More than half of the patients who present with clinical signs such as abdominal bloating and a feeling of fullness already show advanced stages. The majority of ovarian cancers grow as cystic masses, and cancer cells easily spread into the pelvic cavity once the cysts rupture or leak. When the ovarian cancer cells disseminate into the peritoneal cavity, metastatic nests may grow in the cul-de-sac, and in more advanced stages, the peritoneal surfaces of the upper abdomen become the next largest soil for cancer progression. Ascites is also produced frequently in ovarian cancers, which facilitates distant metastasis. Clinicopathologic, epidemiologic and molecular studies on ovarian cancers have improved our understanding and therapeutic approaches, but still further efforts are required to reduce the risks in the patients who are predisposed to this lethal disease and the mortality of the patients in advanced stages. Among various molecules involved in ovarian carcinogenesis, special genes such as TP53, BRCA1 and BRCA2 have been well investigated. These genes are widely accepted as the predisposing factors that trigger malignant transformation of the epithelial cells of the ovary. In addition, adnexal inflammatory conditions such as chronic salpingitis and ovarian endometriosis have been great research interests in the context of carcinogenic background of ovarian cancers. In this review, I discuss the roles of stromal cells and inflammatory factors in the carcinogenesis and progression of ovarian cancers

  3. Environmental and developmental origins of ovarian reserve.

    Science.gov (United States)

    Richardson, M C; Guo, M; Fauser, B C J M; Macklon, N S

    2014-01-01

    BACKGROUND Oocyte number is established early in life before a gradual loss of this ovarian reserve during reproductive life until oocyte availability becomes limiting at the menopause. Although there is a large genetic component to the ovarian reserve achieved before birth, other influences including the maternal endocrine and nutritional milieu, and environmental factors may represent important developmental determinants. Environmental and nutritional factors may also modify the downward trajectory of ovarian reserve in adult life. The combination of these early and later life influences has the potential to lead to diminished ovarian reserve, compromising fertility in later reproductive years and altering age at natural menopause. METHODS Literature searches of the ISI Web of Knowledge database were carried out using the main terms 'ovarian reserve' and 'menopause AND age' in conjunction with a range of other terms encompassing a variety of factors with potential effects on ovarian reserve. The various searches were inspected manually and the relevant papers selected for critical analysis and interpretation. RESULTS Evidence was identified supporting the view that elevated prenatal androgens have an adverse effect on the early establishment of ovarian reserve, although the implications for ovarian reserve in the polycystic ovary syndrome (which may also be programmed through prenatal androgen exposure) remain uncertain. Recent evidence is cited suggesting that effects of maternal nutrient restriction on ovarian reserve may also involve changes in prenatal androgen exposure. A general rationale is developed through examination of evidence which emphasizes the roles of the aryl hydrocarbon receptor (AHR) and the estrogen receptor (ER) systems in ovarian reserve modulation. Because of their similarity to the natural ligands, many environmental compounds have the ability to bind to these receptors (albeit at lower affinities) and thereby have the potential to

  4. Establishment and characterization of an ovarian cell line from Southern catfish (Silurus meridionalis).

    Science.gov (United States)

    Wei, Jing; Qi, WenChuang; Zhou, Yujie; Zhang, Xiaoping; Dong, Ranran; Zhou, Linyan; Wang, Deshou

    2014-10-01

    An ovarian cell line was successfully developed from the juvenile ovary of Southern catfish (SCO1) (Silurus meridionalis), which was designated as SCO1. The cell line multiplied preferentially in L-15 medium with 15 % fetal bovine serum at 28 °C for more than 70 passages over a period of 420 days. SCO1 showed fibroblast-like morphology and predominantly retained a diploid karyotype of 58 chromosomes. From the gene expression patterns, SCO1 showed a characteristic of ovarian granulosa cells. After the cells were transfected with the green fluorescent protein expression vector, bright fluorescent signals could be observed in approximately 30 % cells. This cell line may be valuable for the evaluation of endocrine disruptors and studying interactions between somatic cells and germ cells. PMID:24671650

  5. Safety considerations for transplanting cryopreserved ovarian tissue to restore fertility in female patients who have recovered from Ewing's sarcoma

    DEFF Research Database (Denmark)

    Sørensen, Stine D; Greve, Tine; Wielenga, Vera Timmermans;

    2014-01-01

    Ewing's sarcoma (EWS) is a highly malignant cancer in children, adolescents and young adults. The chemotherapy required to treat female EWS patients may cause primary ovarian insufficiency and infertility as a side effect. Cryopreservation of ovarian tissue before the start of chemotherapy can...... potentially preserve fertility. When the patient has been cured and primary ovarian insufficiency has developed, transplantation of frozen/thawed ovarian tissue can restore ovarian function. The tissue is usually collected before chemotherapy is initiated, and malignant cells may contaminate the stored...... EWS patients and presents a new case of malignant cells in an ovarian biopsy from a girl with EWS....

  6. Anti-Müllerian hormone (AMH) receptor type II expression and AMH activity in bovine granulosa cells.

    Science.gov (United States)

    Poole, Daniel H; Ocón-Grove, Olga M; Johnson, Alan L

    2016-09-15

    Anti-Müllerian hormone (AMH) produced by granulosa cells has previously been proposed to play a role in regulating granulosa cell differentiation and follicle selection. Although AMH receptor type II (AMHR2) dimerizes with a type I receptor to initiate AMH signaling, little is known about the regulation of AMHR2 expression in bovine granulosa cells and the role of AMH in follicle development. The primary objectives of this study were to: (1) characterize AMHR2 expression in granulosa cells during follicle development; (2) identify factors that regulate AMHR2 mRNA expression in granulosa cells; and (3) examine the role of AMH signaling in granulosa cell differentiation and proliferation. Bovine granulosa cells were isolated from 5- to 8-mm follicles before selection and deviation, as well as from 9- to 12-mm and 13- to 24-mm follicles after selection. Analyses revealed that expression of AMHR2 was greater in 5- to 8-mm follicles compared with 13- to 24-mm follicles (P AMH was greater in granulosa cells cultured with BMP2, BMP6, or BMP15 when compared with controls (P AMH, in vitro, inhibited CYP19A1 expression in a dose-related (10-100 ng/mL) fashion, and reduced granulosa cell proliferation at 48 and 72 hours (P AMH signaling plays a role in both regulating granulosa cell proliferation and preventing granulosa cells from 5- to 8-mm follicles from undergoing premature differentiation before follicle selection. PMID:27268296

  7. Ovarian tumors secreting insulin.

    Science.gov (United States)

    Battocchio, Marialberta; Zatelli, Maria Chiara; Chiarelli, Silvia; Trento, Mariangela; Ambrosio, Maria Rosaria; Pasquali, Claudio; De Carlo, Eugenio; Dassie, Francesca; Mioni, Roberto; Rebellato, Andrea; Fallo, Francesco; Degli Uberti, Ettore; Martini, Chiara; Vettor, Roberto; Maffei, Pietro

    2015-08-01

    Combined ovarian germ cell and neuroendocrine tumors are rare. Only few cases of hyperinsulinism due to ovarian ectopic secretion have been hypothesized in the literature. An ovarian tumor was diagnosed in a 76-year-old woman, referred to our department for recurrent hypoglycemia with hyperinsulinism. In vivo tests, in particular fasting test, rapid calcium infusion test, and Octreotide test were performed. Ectopic hyperinsulinemic hypoglycemia was demonstrated in vivo and hypoglycemia disappeared after hysteroadnexectomy. Histological exam revealed an ovarian germ cell tumor with neuroendocrine and Yolk sac differentiation, while immunostaining showed insulin positivity in neuroendocrine cells. A cell culture was obtained by tumoral cells, testing Everolimus, and Pasireotide. Insulin was detected in cell culture medium and Everolimus and Pasireotide demonstrated their potentiality in reducing insulin secretion, more than controlling cell viability. Nine cases of hyperinsulinism due to ovarian ectopic secretion reported in literature have been reviewed. These data confirm the ovarian tissue potentiality to induce hyperinsulinemic hypoglycemic syndrome after neoplastic transformation. PMID:25896552

  8. Pathobiology of ovarian carcinomas

    Institute of Scientific and Technical Information of China (English)

    Mojgan Devouassoux-Shisheboran; Catherine Genestie

    2015-01-01

    Ovarian tumors comprise a heterogeneous group of lesions, displaying distinct tumor pathology and oncogenic potentiel. These tumors are subdivided into three main categories: epithelial, germ cell, and sex-cord stromal tumors. We report herein the newly described molecular abnormalities in epithelial ovarian cancers (carcinomas). Immunohistochemistry and molecular testing help pathologists to decipher the significant heterogeneity of this disease. Our better understanding of the molecular basis of ovarian carcinomas represents the first step in the development of targeted therapies in the near future.

  9. A Mixture Reflecting Polybrominated Diphenyl Ether (PBDE) Profiles Detected in Human Follicular Fluid Significantly Affects Steroidogenesis and Induces Oxidative Stress in a Female Human Granulosa Cell Line.

    Science.gov (United States)

    Lefevre, Pavine L C; Wade, Mike; Goodyer, Cindy; Hales, Barbara F; Robaire, Bernard

    2016-07-01

    Brominated flame retardants are incorporated into consumer products to prevent flame propagation. These compounds leach into the domestic environment, resulting in chronic exposure. Pregnancy failure is associated with high levels of polybrominated diphenyl ethers (PBDEs), a major class of brominated flame retardants, in human follicular fluid, raising serious questions regarding their impact on female fertility. Our goal was to elucidate the effects of a mixture of PBDEs, similar to the profile found in human follicular fluid, on an immortalized human granulosa cell line, the KGN cell line. We showed that cell viability was altered and oxidative stress was induced as reflected by increased reactive oxygen species formation at 100 μM of the PBDE mixture. Transcriptomic analysis revealed that PBDE treatments of 1, 5, and 20 μM altered the expression of several genes involved in the reactive oxygen species signaling pathway. Significant dose-dependent reductions in progesterone and estradiol levels in the culture medium were measured after PBDE treatment; in parallel, the expression of genes involved in estradiol metabolism, namely CYP1A1, was up-regulated by 5 and 20 μM of the PBDE mixture. Treatment with 20 μM PBDE also increased the expression and secretion of the proinflammatory factor, IL-6, into the KGN cell culture medium. Our results demonstrate that PBDEs can alter human granulosa cell functions by inducing oxidative stress and disrupting steroidogenesis. These results indicate that PBDEs may be detrimental to ovarian functions and thus may adversely affect female reproductive health after chronic exposure. PMID:27219277

  10. Specific genes are selectively expressed between cumulus and granulosa cells from individual human pre-ovulatory follicles

    DEFF Research Database (Denmark)

    Grøndahl, M L; Andersen, C Yding; Bogstad, J;

    2012-01-01

    During folliculogenesis the granulosa cells differentiate into two cell types: Cumulus cells (CC) and mural granulosa cells (MGC). The objective of the study was to generate and compare the transcriptomes of MGC and CC from the pre-ovulatory follicle to characterize the detailed profile of the two...

  11. Premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Persani Luca

    2006-04-01

    Full Text Available Abstract Premature ovarian failure (POF is a primary ovarian defect characterized by absent menarche (primary amenorrhea or premature depletion of ovarian follicles before the age of 40 years (secondary amenorrhea. It is a heterogeneous disorder affecting approximately 1% of women e.g. Turner syndrome represent the major cause of primary amenorrhea associated with ovarian dysgenesis. Despite the description of several candidate genes, the cause of POF remains undetermined in the vast majority of the cases. Management includes substitution of the hormone defect by estrogen/progestin preparations. The only solution presently available for the fertility defect in women with absent follicular reserve is ovum donation.

  12. Common Genetic Variation in Circadian Rhythm Genes and Risk of Epithelial Ovarian Cancer (EOC)

    Science.gov (United States)

    Jim, Heather S.L.; Lin, Hui-Yi; Tyrer, Jonathan P.; Lawrenson, Kate; Dennis, Joe; Chornokur, Ganna; Chen, Zhihua; Chen, Ann Y.; Permuth-Wey, Jennifer; Aben, Katja KH.; Anton-Culver, Hoda; Antonenkova, Natalia; Bruinsma, Fiona; Bandera, Elisa V.; Bean, Yukie T.; Beckmann, Matthias W.; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Bunker, Clareann H.; Butzow, Ralf; Campbell, Ian G.; Carty, Karen; Chang-Claude, Jenny; Cook, Linda S.; Cramer, Daniel W.; Cunningham, Julie M.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; du Bois, Andreas; Despierre, Evelyn; Sieh, Weiva; Doherty, Jennifer A.; Dörk, Thilo; Dürst, Matthias; Easton, Douglas F.; Eccles, Diana M.; Edwards, Robert P.; Ekici, Arif B.; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind; Goodman, Marc T.; Gronwald, Jacek; Harter, Philipp; Hasmad, Hanis N.; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A.T.; Hillemanns, Peter; Hogdall, Claus K.; Hogdall, Estrid; Hosono, Satoyo; Iversen, Edwin S.; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y.; Kellar, Melissa; Kiemeney, Lambertus A.; Krakstad, Camilla; Kjaer, Susanne K.; Kupryjanczyk, Jolanta; Vierkant, Robert A.; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W.; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lim, Boon Kiong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F.A.G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; McNeish, Ian; Menon, Usha; Milne, Roger L.; Modugno, Francesmary; Thomsen, Lotte; Moysich, Kirsten B.; Ness, Roberta B.; Nevanlinna, Heli; Eilber, Ursula; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Orsulic, Sandra; Palmieri Weber, Rachel; Paul, James; Pearce, Celeste L.; Pejovic, Tanja; Pelttari, Liisa M.; Pike, Malcolm C.; Poole, Elizabeth M.; Schernhammer, Eva; Risch, Harvey A.; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B.; Siddiqui, Nadeem; Song, Honglin; Southey, Melissa C.; Spiewankiewicz, Beata; Sucheston-Campbell, Lara; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J.; Tangen, Ingvild L.; Tworoger, Shelley S.; van Altena, Anne M.; Vergote, Ignace; Walsh, Christine S.; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S.; Wicklund, Kristine G.; Wilkens, Lynne R.; Wu, Anna H.; Wu, Xifeng; Woo, Yin-Ling; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Amankwah, Ernest; Berchuck, Andrew; Schildkraut, Joellen M.; Kelemen, Linda E.; Ramus, Susan J.; Monteiro, Alvaro N.A.; Goode, Ellen L.; Narod, Steven A.; Gayther, Simon A.; Pharoah, Paul D. P.; Sellers, Thomas A.; Phelan, Catherine M.

    2016-01-01

    Disruption in circadian gene expression, whether due to genetic variation or environmental factors (e.g., light at night, shiftwork), is associated with increased incidence of breast, prostate, gastrointestinal and hematologic cancers and gliomas. Circadian genes are highly expressed in the ovaries where they regulate ovulation; circadian disruption is associated with several ovarian cancer risk factors (e.g., endometriosis). However, no studies have examined variation in germline circadian genes as predictors of ovarian cancer risk and invasiveness. The goal of the current study was to examine single nucleotide polymorphisms (SNPs) in circadian genes BMAL1, CRY2, CSNK1E, NPAS2, PER3, REV1 and TIMELESS and downstream transcription factors KLF10 and SENP3 as predictors of risk of epithelial ovarian cancer (EOC) and histopathologic subtypes. The study included a test set of 3,761 EOC cases and 2,722 controls and a validation set of 44,308 samples including 18,174 (10,316 serous) cases and 26,134 controls from 43 studies participating in the Ovarian Cancer Association Consortium (OCAC). Analysis of genotype data from 36 genotyped SNPs and 4600 imputed SNPs indicated that the most significant association was rs117104877 in BMAL1 (OR = 0.79, 95% CI = 0.68–0.90, p = 5.59 × 10−4]. Functional analysis revealed a significant down regulation of BMAL1 expression following cMYC overexpression and increasing transformation in ovarian surface epithelial (OSE) cells as well as alternative splicing of BMAL1 exons in ovarian and granulosa cells. These results suggest that variation in circadian genes, and specifically BMAL1, may be associated with risk of ovarian cancer, likely through disruption of hormonal pathways. PMID:26807442

  13. Telocytes as potential targets in a cyclophosphamide-induced animal model of premature ovarian failure.

    Science.gov (United States)

    Liu, Te; Wang, Suwei; Li, Qiong; Huang, Yongyi; Chen, Chuan; Zheng, Jin

    2016-09-01

    Premature ovarian failure (POF) refers to the presence of ovarian atrophic permanent amenorrhea in women under the age of 40. The pathogenesis of POF remains to be fully elucidated. Telocytes are a group of specialized cells with a small cell volume and very long cytoplasmic prolongations with dichotomous branching. Previous studies have indicated that telocytes function to support the trachea and serve as stem cell niches. Although it has been confirmed that telocytes are present in numerous organs in mammals, it remains to be determined whether they are present in ovarian tissues and whether they are involved in the development of POF. The present study used a cyclophosphamide-induced mouse model of POF. Hematoxylin and eosin staining and an enzyme‑linked immunosorbent assay revealed that cyclophosphamide induced edema and apoptosis of ovarian stromal and granulosa cells and increased atretic follicles. In addition, cyclophosphamide induced abnormal peripheral blood FSH and E2 levels in mice. Transmission electron microscopy revealed a small number of telocyte‑like cell structures in the ovarian stroma of wild‑type mice. In addition, flow cytometry and immunohistochemical staining results suggested that the number of cluster of differentiation (CD)34/platelet‑derived growth factor receptor (PDGFR)α, CD34/PDGFRβ and CD34/vimentin double‑positive cells in the ovaries of POF mice was significantly decreased compared with wild‑type mice. In conclusion, mouse ovarian tissues appear to contain telocytes, and cyclophosphamide treatment significantly reduced the number of ovarian telocytes. Therefore, telocytes may serve as a potential novel marker of POF induced by cyclophosphamide. PMID:27485835

  14. Ectopic ovarian pregnancy

    International Nuclear Information System (INIS)

    A case of ectopic ovarian pregnancy is presented occurring in a 24 years old woman after natural conception. The clinical diagnosis was ruptured tubal pregnancy. Gross findings were suggestive of ruptured corpus luteum cyst on exploration. The histopathological examination of specimen brought forward the diagnosis of ovarian pregnancy. (author)

  15. Effect of the human follicle-stimulating hormone-binding inhibitor and its N-terminal fragment on follicle-stimulating hormone-induced progesterone secretion by granulosa cells in vitro

    Indian Academy of Sciences (India)

    Perinaaz R Wadia; Smita D Mahale; Tarala D Nandedkar

    2007-09-01

    Intrafollicular factors play an important role in folliculogenesis. The follicle-stimulating hormone (FSH)-binding inhibitor (FSHBI), purified by our laboratory from human ovarian follicular fluid, has been shown to suppress ovulation and induce follicular atresia/apoptosis in mice as well as impair fertility in marmosets, the new world monkeys. The octapeptide, a peptide corresponding to the N-terminal region of human FSHBI (hFSHBI), has been synthesized and also shows FSHBI activity in vitro. In the present study, we have attempted to identify the mechanism of action of the peptide in granulosa cell cultures. Rat granulosa cell cultures were treated with varying concentrations of the octapeptide or partially purified hFSHBI (gel chromatography fraction hGF2) in the presence or absence of human FSH (hFSH) and the amount of progesterone (P4) secreted in the culture supernatants after 3 h/48 h was estimated. Both hGF2 and the octapeptide failed to alter basal levels as well as 8-bromo cAMP-induced P4 production, while FSH-induced P4 secretion was inhibited in a dose-dependent manner. These studies reveal that the octapeptide, a fragment of FSHBI, and the native protein have similar activity in vitro and both compounds alter FSH action at the receptor level upstream of cAMP formation.

  16. Amygdala Kindling Alters Estrus Cycle and Ovarian Morphology in the Rat.

    Science.gov (United States)

    Pan, Juan; Zhang, Lingwu; Wang, Feng; Liu, Dan; Li, P Andy; Sun, Tao

    2013-11-01

    The objective of this study is to explore the effects of amygdala kindling on estrus cycle and ovarian morphology. Thirty-five female rats at the age of 8 weeks were randomly designated to electrode kindled, sham-kindled, and normal controls. Kindled rats were implanted with kindling electrodes in the left basolateral amygdala and kindled by brief suprathreshold stimulations with a bipolar electrode. Estrous cycles were daily monitored through vaginal smears. Electrographic and behavioral seizures were recorded and ovarian morphology was evaluated by light and electron microscopies. Our results showed that the kindled rats lost their ovarian periodicity displayed significant ovarian enlargement. H&E staining revealed increased number of growing follicles and total follicles, as well as polycysts in the ovaries of the kindled animals compared to sham and control animals. Ultrastructural study detected numerous apoptotic granulosa cells in growing follicles and thecal cell hyperplasia with secretary granules in the thecal cells in the kindled rats. The results suggest that amygdala kindling is a risk factor for the development of polycystic ovary syndrome.

  17. Chicken lutropin acts like follitropin in rat ovarian follitropin receptor: an isoelectric focusing study.

    Science.gov (United States)

    Iwasawa, A; Hattori, M; Fukuhara, Y; Kawashima, M; Wakabayashi, K; Kamiyoshi, M

    1998-07-01

    This study investigates whether chicken lutropin (LH) specifically binds to rat ovarian follitropin (FSH) receptor and exerts FSH-like bioactivity. Glycoprotein fraction, prepared from the chicken anterior pituitary gland, was fractionated using isoelectric focusing within a pH range of 3.5-11. Analysis of the focused fractions, by a radioreceptor assay (RRA) specific for FSH in rats using rat ovarian homogenate as receptor source, and 125I-labeled rat FSH as radioligand, detected a large component having an isoelectric point of 10.25. This focusing profile obtained by RRA was quite similar to that obtained by a specific radioimmunoassay (RIA) for chicken LH, but clearly different from that obtained by a specific RIA for chicken FSH, indicating this RRA specifically recognizes chicken LH. Chicken LH fraction prepared from the electrofocused material was used for further studies. The chicken LH preparation was three times more potent than rat FSH in the RRA in displacing the radioligand bound to rat ovarian receptor, while chicken LH facilitated an 8-fold less production of estradiol in dispersed rat granulosa cells than rat FSH. These results suggest that chicken LH acts like rat FSH in rat ovarian FSH receptor, but receptor-binding activity is much higher than biological activity. PMID:9827020

  18. Gene expression profiling supports the hypothesis that human ovarian surface epithelia are multipotent and capable of serving as ovarian cancer initiating cells

    Directory of Open Access Journals (Sweden)

    Matyunina Lilya V

    2009-12-01

    Full Text Available Abstract Background Accumulating evidence suggests that somatic stem cells undergo mutagenic transformation into cancer initiating cells. The serous subtype of ovarian adenocarcinoma in humans has been hypothesized to arise from at least two possible classes of progenitor cells: the ovarian surface epithelia (OSE and/or an as yet undefined class of progenitor cells residing in the distal end of the fallopian tube. Methods Comparative gene expression profiling analyses were carried out on OSE removed from the surface of normal human ovaries and ovarian cancer epithelial cells (CEPI isolated by laser capture micro-dissection (LCM from human serous papillary ovarian adenocarcinomas. The results of the gene expression analyses were randomly confirmed in paraffin embedded tissues from ovarian adenocarcinoma of serous subtype and non-neoplastic ovarian tissues using immunohistochemistry. Differentially expressed genes were analyzed using gene ontology, molecular pathway, and gene set enrichment analysis algorithms. Results Consistent with multipotent capacity, genes in pathways previously associated with adult stem cell maintenance are highly expressed in ovarian surface epithelia and are not expressed or expressed at very low levels in serous ovarian adenocarcinoma. Among the over 2000 genes that are significantly differentially expressed, a number of pathways and novel pathway interactions are identified that may contribute to ovarian adenocarcinoma development. Conclusions Our results are consistent with the hypothesis that human ovarian surface epithelia are multipotent and capable of serving as the origin of ovarian adenocarcinoma. While our findings do not rule out the possibility that ovarian cancers may also arise from other sources, they are inconsistent with claims that ovarian surface epithelia cannot serve as the origin of ovarian cancer initiating cells.

  19. Biological versus chronological ovarian age: implications for assisted reproductive technology

    Directory of Open Access Journals (Sweden)

    Tredway Donald

    2009-09-01

    Full Text Available Abstract Background Women have been able to delay childbearing since effective contraception became available in the 1960s. However, fertility decreases with increasing maternal age. A slow but steady decrease in fertility is observed in women aged between 30 and 35 years, which is followed by an accelerated decline among women aged over 35 years. A combination of delayed childbearing and reduced fecundity with increasing age has resulted in an increased number and proportion of women of greater than or equal to 35 years of age seeking assisted reproductive technology (ART treatment. Methods Literature searches supplemented with the authors' knowledge. Results Despite major advances in medical technology, there is currently no ART treatment strategy that can fully compensate for the natural decline in fertility with increasing female age. Although chronological age is the most important predictor of ovarian response to follicle-stimulating hormone, the rate of reproductive ageing and ovarian sensitivity to gonadotrophins varies considerably among individuals. Both environmental and genetic factors contribute to depletion of the ovarian oocyte pool and reduction in oocyte quality. Thus, biological and chronological ovarian age are not always equivalent. Furthermore, biological age is more important than chronological age in predicting the outcome of ART. As older patients present increasingly for ART treatment, it will become more important to critically assess prognosis, counsel appropriately and optimize treatment strategies. Several genetic markers and biomarkers (such as anti-Müllerian hormone and the antral follicle count are emerging that can identify women with accelerated biological ovarian ageing. Potential strategies for improving ovarian response include the use of luteinizing hormone (LH and growth hormone (GH. When endogenous LH levels are heavily suppressed by gonadotrophin-releasing hormone analogues, LH supplementation may help

  20. Production of tissue inhibitors of metalloproteinases (TIMPs) by pig ovarian cells in vivo and the effect of TIMP-1 on steroidogenesis in vitro.

    Science.gov (United States)

    Shores, E M; Hunter, M G

    2000-09-01

    Precisely which ovarian cells produce tissue inhibitors of metalloproteinases (TIMPs) is unclear. Although granulosa cells are reported to produce TIMPs, thecal TIMP production has not been investigated nor has the influence of TIMPs on theca cells. Furthermore, although periovulatory follicles have been examined, little is known about smaller ovarian follicles. Follicles >/= 2 mm in diameter were collected from Large White hybrid gilts on the day before predicted oestrus (n = 3) or after hCG treatment (n = 3) and divided into 1 mm size classes. Small (2 to /= 5 mm were separated into follicular fluid, granulosa and theca cell compartments. After homogenization, TIMP-1, -2 and -3 were detected by reverse zymography. Theca cells (50 x 10(3) per well) were cultured with TIMP-1 (10, 100 or 200 ng ml(-1) with or without long-R3 insulin-like growth factor I (IGF-I)) in a serum-free system to investigate the effect on steroidogenesis and the number of cells. Both large and small pig follicles produced TIMPs and TIMP-1, -2 and -3 were detected in follicular fluid, granulosa and theca cell samples. There was a phase x tissue type interaction for the presence of both TIMP-1 and -2 (P 0.05), and the highest concentrations occurred in the theca tissue. There were tissue type x follicle size interactions for the presence of both TIMP-1 and -2 (P < 0.001). In vitro, TIMP-1 increased thecal steroidogenesis after 144 h (oestradiol, P < 0.05, progesterone, P < 0.001) but reduced the number of viable cells (P < 0.001). In conclusion, TIMP-1, -2 and -3 were present in large and small pig follicles and were produced by both granulosa and theca cells, although concentrations differed with the type of tissue. Production was regulated by factors including follicle size and phase of the oestrous cycle. In addition to controlling tissue remodelling, TIMP-1 may also regulate steroidogenesis. PMID:11006148

  1. Biomarkers of Ovarian Reserve

    Directory of Open Access Journals (Sweden)

    William E. Roudebush

    2008-01-01

    Full Text Available The primary function of the female ovary is the production of a mature and viable oocyte capable of fertilization and subsequent embryo development and implantation. At birth, the ovary contains a finite number of oocytes available for folliculogenesis. This finite number of available oocytes is termed “the ovarian reserve”. The determination of ovarian reserve is important in the assessment and treatment of infertility. As the ovary ages, the ovarian reserve will decline. Infertility affects approximately 15-20% of reproductive aged couples. The most commonly used biomarker assay to assess ovarian reserve is the measurement of follicle stimulating hormone (FSH on day 3 of the menstrual cycle. However, antimüllerian hormone and inhibin-B are other biomarkers of ovarian reserve that are gaining in popularity since they provide direct determination of ovarian status, whereas day 3 FSH is an indirect measurement. This review examines the physical tools and the hormone biomarkers used to evaluate ovarian reserve.

  2. Effect of Monochromatic Light on Expression of Estrogen Receptor (ER) and Progesterone Receptor (PR) in Ovarian Follicles of Chicken.

    Science.gov (United States)

    Liu, Lingbin; Li, Diyan; Gilbert, Elizabeth R; Xiao, Qihai; Zhao, Xiaoling; Wang, Yan; Yin, Huadong; Zhu, Qing

    2015-01-01

    Artificial illumination is widely used in modern poultry houses and different wavelengths of light affect poultry production and behaviour. In this study, we measure mRNA and protein abundance of estrogen receptors (ERs) and progesterone receptors (PRs) in order to investigate the effect of monochromatic light on egg production traits and gonadal hormone function in chicken ovarian follicles. Five hundred and fifty-two 19-wk-old laying hens were exposed to three monochromatic lights: red (RL; 660 nm), green (GL; 560 nm), blue (BL; 480 nm) and control cool white (400-760 nm) light with an LED (light-emitting diode). There were 4 identical light-controlled rooms (n = 138) each containing 3 replicate pens (46 birds per pen). Water was supplied ad libitum and daily rations were determined according to the nutrient suggestions for poultry. Results showed that under BL conditions there was an increase in the total number of eggs at 300 days of age and egg-laying rate during the peak laying period. The BL and GL extended the duration of the peak laying period. Plasma melatonin was lowest in birds reared under BL. Plasma estradiol was elevated in the GL-exposed laying hens, and GL and BL increased progesterone at 28 wk of age. In the granulosa layers of the fifth largest preovulatory follicle (F5), the third largest preovulatory follicle (F3) and the largest preovulatory follicle (F1), ERα mRNA was increased by BL and GL. Treatment with BL increased ERβ mRNA in granulosa layers of F5, F3 and F1, while GL increased ERβ mRNA in F5 and F3. There was a corresponding increase in abundance of the proteins in the granulosa layers of F5, with an increase in PR-B, generated via an alternative splice site, relative to PR-A. Treatment with BL also increased expression of PR mRNA in all of the granulosa layers of follicles, while treatment with GL increased expression of PR mRNA in granulosa layers of SYF(small yellow follicle), F5 and F1. These results indicate that blue and green

  3. Effect of Monochromatic Light on Expression of Estrogen Receptor (ER and Progesterone Receptor (PR in Ovarian Follicles of Chicken.

    Directory of Open Access Journals (Sweden)

    Lingbin Liu

    Full Text Available Artificial illumination is widely used in modern poultry houses and different wavelengths of light affect poultry production and behaviour. In this study, we measure mRNA and protein abundance of estrogen receptors (ERs and progesterone receptors (PRs in order to investigate the effect of monochromatic light on egg production traits and gonadal hormone function in chicken ovarian follicles. Five hundred and fifty-two 19-wk-old laying hens were exposed to three monochromatic lights: red (RL; 660 nm, green (GL; 560 nm, blue (BL; 480 nm and control cool white (400-760 nm light with an LED (light-emitting diode. There were 4 identical light-controlled rooms (n = 138 each containing 3 replicate pens (46 birds per pen. Water was supplied ad libitum and daily rations were determined according to the nutrient suggestions for poultry. Results showed that under BL conditions there was an increase in the total number of eggs at 300 days of age and egg-laying rate during the peak laying period. The BL and GL extended the duration of the peak laying period. Plasma melatonin was lowest in birds reared under BL. Plasma estradiol was elevated in the GL-exposed laying hens, and GL and BL increased progesterone at 28 wk of age. In the granulosa layers of the fifth largest preovulatory follicle (F5, the third largest preovulatory follicle (F3 and the largest preovulatory follicle (F1, ERα mRNA was increased by BL and GL. Treatment with BL increased ERβ mRNA in granulosa layers of F5, F3 and F1, while GL increased ERβ mRNA in F5 and F3. There was a corresponding increase in abundance of the proteins in the granulosa layers of F5, with an increase in PR-B, generated via an alternative splice site, relative to PR-A. Treatment with BL also increased expression of PR mRNA in all of the granulosa layers of follicles, while treatment with GL increased expression of PR mRNA in granulosa layers of SYF(small yellow follicle, F5 and F1. These results indicate that blue

  4. Ovarian stem cells: From basic to clinical applications

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    The field of reproductive biology has undergone significantdevelopments in the last decade. The notion thatthere is a fixed reserve pool of oocytes before birth wasestablished by Zuckerman in 1951. However, in 2004,an article published in nature challenged this centraldogma of mammalian reproductive biology. Tilly's groupreported the existence of ovarian germline stem cells(GSCs) in postnatal ovaries of mice and suggested thatthe bone marrow could be an extragonadal source ofovarian GSCs. These findings were strongly criticized;however, several independent groups have sincesuccessfully isolated and characterized ovarian GSCsin postnatal mice. The ovarian GSCs are located in theovarian surface epithelium and express markers ofundifferentiated GSCs. When transplanted into mouseovaries, mouse ovarian GSCs could differentiate andproduce embryos and offspring. Similarly, in a recentstudy, ovarian GSCs were found to be present in theovaries of women of reproductive age. Conversely,there is increasing evidence that stem cells responsiblefor maintaining a healthy state in normal tissue maybe a source of some cancers, including ovarian cancer.Cancer stem cells (CSCs) have been found in manytissues, including ovaries. Some researchers havesuggested that ovarian cancer may be a result of thetransformation and dysfunction of ovarian GSCs withself-renewal properties. Drug resistant and metastasisgeneratingCSCs are responsible for many importantproblems affecting ovarian cancer patients. Therefore,the identification of CSCs will provide opportunitiesfor the development of new therapeutic strategies fortreatments for infertility and ovarian cancer. In thisarticle, we summarize the current understanding ofovarian GSCs in adult mammals, and we also discusswhether there is a relationship between GSCs and CSCs.

  5. Pilidiella tibouchinae sp. nov. associated with foliage blight of Tibouchina granulosa (quaresmeira) in Brazil

    NARCIS (Netherlands)

    Miranda, B.E.; Barreto, R.W.; Crous, P.W.; Groenewald, J.Z.

    2012-01-01

    Tibouchina granulosa (Melastomataceae), Brazilian glorytree (Brazilian common name - quaresmeira), a common tree of the Atlantic Forest of Brazil, is widely used as an ornamental for its violet or pink blossoms. Little is known about fungal diseases affecting this species, although these represent a

  6. Androgen and FSH synergistically stimulate lipoprotein degradation and utilization by ovary granulosa cells

    International Nuclear Information System (INIS)

    Androgen can directly modulate the induction of steroidogenic enzymes by FSH (follicle stimulating hormone) in ovary granulosa cells. In studies of its mechanism of action, the authors examined the androgen effect on granulosa cell interaction with lipoproteins, the physiologic source of cholesterol. After granulosa cells were cultured for 48 hours with and without androgen and/or FSH, the cells were incubated for 24 hours with 125I-lipoproteins [human high density lipoprotein (HDL), rat HDL, or human low density lipoprotein (LDL)]. The media were then analyzed for lipoprotein protein coat degradation products (mainly 125I-monoiodotyrosine) and progestin [mainly 20 alpha-dihydroprogesterone (20 alpha-DHP)]. In the absence of FSH and androgen, 2 X 10(5) granulosa cells degraded basal levels of all three lipoproteins, but produced no measurable 20 alpha-DHP. The addition of 10(-7) M androstenedione (A), testosterone (T), or 5 alpha-dihydrotestosterone (DHT) had no effect on lipoprotein protein degradation or 20 alpha-DHP production. FSH alone stimulated lipoprotein protein degradation by 50 to 300% while the addition of androgen synergistically augmented the FSH-stimulated 20 alpha-DHP production as well as protein coat degradation of all three lipoproteins. DHT and T were both effective, indicating that androgens themselves, and not estrogen products, were responsible for the effect on lipoprotein protein degradation and 20 alpha-DHP production

  7. Surgical removal of a mammary adenocarcinoma and a granulosa cell tumor in an African pygmy hedgehog.

    Science.gov (United States)

    Wellehan, James F X; Southorn, Erin; Smith, Dale A; Taylor, W Michael

    2003-03-01

    A 3-year-old, female African pygmy hedgehog (Atelerix albiventris) was referred with a history of hematuria. Hyperglycemia and glucosuria were found at presentation. Mammary adenocarcinoma and a granulosa cell tumor were found and removed surgically. Glucosuria and hematuria resolved, and the hedgehog has done well for 10 mo postoperatively. PMID:12677695

  8. Surgical removal of a mammary adenocarcinoma and a granulosa cell tumor in an African pygmy hedgehog

    OpenAIRE

    Wellehan, James F. X.; Southorn, Erin; Smith, Dale A.; Taylor, Michael

    2003-01-01

    A 3-year-old, female African pygmy hedgehog (Atelerix albiventris) was referred with a history of hematuria. Hyperglycemia and glucosuria were found at presentation. Mammary adenocarcinoma and a granulosa cell tumor were found and removed surgically. Glucosuria and hematuria resolved, and the hedgehog has done well for 10 mo postoperatively.

  9. Anti-Mullerian hormone recruits BMPR-IA in immature granulosa cells.

    Directory of Open Access Journals (Sweden)

    Lauriane Sèdes

    Full Text Available Anti-Müllerian hormone (AMH is a member of the TGF-β superfamily secreted by the gonads of both sexes. This hormone is primarily known for its role in the regression of the Müllerian ducts in male fetuses. In females, AMH is expressed in granulosa cells of developing follicles. Like other members of the TGF-β superfamily, AMH transduces its signal through two transmembrane serine/threonine kinase receptors including a well characterized type II receptor, AMHR-II. The complete signalling pathway of AMH involving Smads proteins and the type I receptor is well known in the Müllerian duct and in Sertoli and Leydig cells but not in granulosa cells. In addition, few AMH target genes have been identified in these cells. Finally, while several co-receptors have been reported for members of the TGF-β superfamily, none have been described for AMH. Here, we have shown that none of the Bone Morphogenetic Proteins (BMPs co-receptors, Repulsive guidance molecules (RGMs, were essential for AMH signalling. We also demonstrated that the main Smad proteins used by AMH in granulosa cells were Smad 1 and Smad 5. Like for the other AMH target cells, the most important type I receptor for AMH in these cells was BMPR-IA. Finally, we have identified a new AMH target gene, Id3, which could be involved in the effects of AMH on the differentiation of granulosa cells and its other target cells.

  10. Competence Classification of Cumulus and Granulosa Cell Transcriptome in Embryos Matched by Morphology and Female Age

    DEFF Research Database (Denmark)

    Borup, Rehannah; Thuesen, Lea Langhoff; Andersen, Claus Yding;

    2016-01-01

    OBJECTIVE: By focussing on differences in the mural granulosa cell (MGC) and cumulus cell (CC) transcriptomes from follicles resulting in competent (live birth) and non-competent (no pregnancy) oocytes the study aims on defining a competence classifier expression profile in the two cellular...

  11. Inhibition of NF-κB promotes autophagy via JNK signaling pathway in porcine granulosa cells.

    Science.gov (United States)

    Gao, Hui; Lin, Lu; Haq, Ihtesham Ul; Zeng, Shen-Ming

    2016-04-22

    The transcription factor nuclear factor-κB (NF-κB) plays an important role in diverse processes, including cell proliferation and differentiation, apoptosis and inflammation. However, the role of NF-κB in porcine follicle development is not clearly elucidated. In this study, we demonstrated that follicle stimulating hormone (FSH) increased the level of inhibitor of NF-κB (IκB) protein and promoted the cytoplasmic localization of p65, indicating that FSH inhibits the activation of NF-κB in porcine granulosa cells. Moreover, inhibition of NF-κB by FSH or another specific inhibitor of NF-κB, pyrrolidine dithiocarbamate (PDTC), could activate JNK signaling and enhance autophagic activity in porcine granulosa cells. Knockdown of RelA (p65) Subunit of NF-κB by RNA interference abrogated the activation of JNK signaling pathway and the increase of autophagic protein expression by FSH. Meanwhile, the functional significance of FSH or PDTC-mediated autophagy were further investigated. Our results demonstrated that the increased autophagy promoted progesterone secretion in porcine granulosa cells. Blockage of autophagy by chloroquine obviated the FSH or PDTC-induced progesterone production. Taken together, these results indicate that inhibition of NF-κB increased autophagy via JNK signaling, and promote steroidogenesis in porcine granulosa cells. Our results provide new insights into the regulation and function of autophagy in mammalian follicle development. PMID:27016483

  12. Connexin 37 and 43 gene and protein expression and developmental competence of isolated ovine secondary follicles cultured in vitro after vitrification of ovarian tissue.

    Science.gov (United States)

    Sampaio da Silva, Andréa Moreira; Bruno, Jamily Bezerra; de Lima, Laritza Ferreira; Ribeiro de Sá, Naíza Arcângela; Lunardi, Franciele Osmarini; Ferreira, Anna Clara Accioly; Vieira Correia, Hudson Henrique; de Aguiar, Francisco Léo Nascimento; Araújo, Valdevane Rocha; Lobo, Carlos Henrique; de Alencar Araripe Moura, Arlindo; Campello, Cláudio Cabral; Smitz, Johan; de Figueiredo, José Ricardo; Ribeiro Rodrigues, Ana Paula

    2016-05-01

    Cryoinjuries caused by vitrification of tissues and organs lead to the loss of membrane proteins that mediate intercellular communications, such as connexins 37 (Cx37) and 43 (Cx43). Thus, the present study aimed to evaluate ovine Cx37 and Cx43 gene and protein expressions and developmental competence by in vitro-cultured secondary follicles retrieved from vitrified ovarian tissue. Ovarian fragments for the same ovary pair were distributed into six treatments: (1) fresh ovarian tissue (FOT); (2) vitrified ovarian tissue (VOT); (3) isolated follicles from fresh ovarian tissue (FIF); (4) isolated follicles from vitrified ovarian tissue; (5) isolated follicles from fresh ovarian tissue followed by in vitro culture (CFIF); (6) isolated follicles from vitrified ovarian tissue followed by in vitro culture (CVIF). In all treatments, Cx37 and Cx43 gene and protein expression patterns were evaluated by reverse transcription polymerase chain reaction and immunocytochemistry. In addition, secondary follicles were analyzed according to follicular integrity and growth, apoptosis, and cell proliferation. In vitro-cultured secondary follicles (CFIF and CVIF) were evaluated based on morphology (extruded follicles), antrum formation, and viability. The percentage of intact follicles was higher, whereas antrum formation, oocyte extrusion rate, and follicle viability were lower in CVIF than in CFIF treatment (P  0.05). Cx37 and Cx43 immunolabeling was localized mainly on granulosa cells and oocytes, respectively. In conclusion, isolation of ovine secondary follicles could be done successfully after vitrification of ovarian tissue, and the basement membrane integrity remained intact after in vitro culture. Although the gene and protein expression of Cx37 did not change after vitrification of ovarian tissue, Cx43 turned out to be altered in secondary follicles after vitrification and in vitro culture. PMID:26876055

  13. Ovarian reserve tests

    Directory of Open Access Journals (Sweden)

    Padma Rekha Jirge

    2011-01-01

    Full Text Available Ovarian reserve plays a crucial role in achieving pregnancy following any treatment in subfertile women. The estimation of ovarian reserve is routinely performed through various ovarian reserve tests (ORTs in an effort to predict the response and outcome in couples prior to In Vitro Fertilization and counsel them. Most widely used tests are basal follicle stimulating hormone and anti-Mullerian hormone and antral follicle count. The role of ORTs in our routine practice is discussed in this article. A MEDLINE search was done to identify suitable articles for review.

  14. Premature ovarian failure and ovarian autoimmunity

    NARCIS (Netherlands)

    J.A. Schoemaker (Joop); H.A. Drexhage (Hemmo); A. Hoek (Annemieke)

    1997-01-01

    textabstractPremature ovarian failure (POF) is defined as a syndrome characterized by menopause before the age of 40 yr. The patients suffer from anovulation and hypoestrogenism. Approximately 1% of women will experience menopause before the age of 40 yr. POF is a heter

  15. Ovarian Cancer Stage I

    Science.gov (United States)

    ... An inset shows cancer cells in the pelvic peritoneum. Also shown are the fallopian tubes, uterus, cervix, ... c) cancer cells are found in the pelvic peritoneum. Topics/Categories: Anatomy -- Gynecologic Cancer Types -- Ovarian Cancer ...

  16. Ovarian reserve parameters

    DEFF Research Database (Denmark)

    Bentzen, J G; Forman, Julie Lyng; Pinborg, Anja;

    2012-01-01

    It remains controversial whether anti-Müllerian hormone (AMH) concentration is influenced by hormonal contraception. This study quantified the effect of hormonal contraception on both endocrine and sonographic ovarian reserve markers in 228 users and 504 non-users of hormonal contraception. On day...... concentration and AFC may not retain their accuracy as predictors of ovarian reserve in women using hormonal contraception. Serum anti-Müllerian hormone (AMH) concentration is an indirect marker of the number of small follicles in the ovary and thereby the ovarian reserve. The AMH concentration is now widely...... 2-5 of the menstrual cycle or during withdrawal bleeding, blood sampling and transvaginal sonography was performed. After adjusting for age, ovarian reserve parameters were lower among users than among non-users of hormonal contraception: serum AMH concentration by 29.8% (95% CI 19.9 to 38...

  17. Ovarian Cancer Statistics

    Science.gov (United States)

    ... population data for older age groups are available. Statistics at a Glance Show More At a Glance ... with ovarian cancer in the United States. Survival Statistics Show More How Many People Survive 5 Years ...

  18. Management of ovarian cysts

    DEFF Research Database (Denmark)

    Knudsen, Ulla Breth; Tabor, Ann; Mosgaard, Berit Jul;

    2004-01-01

    BACKGROUND: The treatment of an ovarian cyst relies on its nature, and accurate preoperative discrimination of benign and malignant cysts is therefore of crucial importance. This study was undertaken to review the literature concerning the preoperative diagnosis and treatment of ovarian cysts....... METHODS: Articles concerning ovarian cysts from a medline literature search during the period 1985-2003 were included in addition to articles found as references in the initial publications. RESULTS: Different methods for discriminating between benign and malignant ovarian cysts are discussed....... The diagnosis and the treatment are assessed in relation to age, menopausal status, pregnancy, and whether the cyst is presumed to be benign or malignant. In general, expectant management is the choice in premenopausal and pregnant women with non-suspicious cysts and normal levels of CA-125. In postmenopausal...

  19. Ovarian localization of 11β-hydroxysteroid dehydrogenase (11βHSD): effects of ACTH stimulation and its relationship with bovine cystic ovarian disease.

    Science.gov (United States)

    Amweg, A N; Salvetti, N R; Stangaferro, M L; Paredes, A H; Lara, H H; Rodríguez, F M; Ortega, H H

    2013-10-01

    Cystic ovarian disease (COD) is an important cause of infertility in cattle, and ACTH has been involved in regulatory mechanisms related to ovarian function associated with ovulation, steroidogenesis, and luteal function. Here, we examined the localization of 11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) and 11βHSD2 proteins in the ovary of healthy cows and animals with spontaneous and ACTH-induced COD and the in vitro response of the follicular wall exposed to ACTH. After stimulation by ACTH, we documented changes in 11βHSD expression and cortisol secretion by the follicular wall of large antral and follicular cysts. Follicular cysts showed a higher constitutive expression of both enzymes, whereas ACTH induced an increase in 11βHSD1 in tertiary follicles and follicular cysts and a decrease in 11βHSD2 in follicular cysts. Moderate expression of 11βHSD1 was observed by immunohistochemistry in granulosa of control animals, with an increase (P cortisol in COD pathogenesis and in regulatory mechanisms of ovarian function.

  20. Epidemiology of ovarian malignancies

    Directory of Open Access Journals (Sweden)

    Akanksha Sood

    2016-01-01

    Conclusions: The epidemiology and presentation of ovarian tumours has remained unchanged since last 3 decades. Nulliparity is not as significant a factor in the aetiology of ovarian malignancy however contraception leading to anovulatory cycles (OC pills may have a protective role. Infertility can be suggested as a risk factor but the treatment for infertility and its role in oncogenesis remains controversial. [Int J Reprod Contracept Obstet Gynecol 2016; 5(1.000: 186-193

  1. Childhood Ovarian Malignancy

    OpenAIRE

    Mahadik, Kalpana; Ghorpade, Kanchanmala

    2014-01-01

    Objective of this article is to appraise diagnostic aspects and treatment modalities in childhood ovarian tumor in background of available evidence. Literature search on Pubmed revealed various aspects of epidemiology, histopathological diagnosis, and treatment of pediatric ovarian tumor. 85 % of childhood tumors are germ cell tumors. The varied histopathological picture in germ cell tumors poses a diagnostic and therapeutic challenge. Immunohistochemistry and newer genetic markers like SALL4...

  2. Pathobiology of ovarian carcinomas

    OpenAIRE

    Mojgan Devouassoux-Shisheboran; Catherine Genestie

    2015-01-01

    Ovarian tumors comprise a heterogeneous group of lesions, displaying distinct tumor pathology and oncogenic potentiel. These tumors are subdivided into three main categories: epithelial, germ cell, and sex-cord stromal tumors. We report herein the newly described molecular abnormalities in epithelial ovarian cancers (carcinomas). Immunohistochemistry and molecular testing help pathologists to decipher the significant heterogeneity of this disease. Our better understanding of the molecular bas...

  3. Role of Growth Differentiation Factor 9 and Bone Morphogenetic Protein 15 in Ovarian Function and Their Importance in Mammalian Female Fertility - A Review.

    Science.gov (United States)

    de Castro, Fernanda Cavallari; Cruz, Maria Helena Coelho; Leal, Claudia Lima Verde

    2016-08-01

    Growth factors play an important role during early ovarian development and folliculogenesis, since they regulate the migration of germ cells to the gonadal ridge. They also act on follicle recruitment, proliferation/atresia of granulosa cells and theca, steroidogenesis, oocyte maturation, ovulation and luteinization. Among the growth factors, the growth differentiation factor 9 (GDF9) and the bone morphogenetic protein 15 (BMP15), belong to the transforming growth factor beta (TGF-β) superfamily, have been implicated as essential for follicular development. The GDF9 and BMP15 participate in the evolution of the primordial follicle to primary follicle and play an important role in the later stages of follicular development and maturation, increasing the steroidogenic acute regulatory protein expression, plasminogen activator and luteinizing hormone receptor (LHR). These factors are also involved in the interconnections between the oocyte and surrounding cumulus cells, where they regulate absorption of amino acids, glycolysis and biosynthesis of cholesterol cumulus cells. Even though the mode of action has not been fully established, in vitro observations indicate that the factors GDF9 and BMP15 stimulate the growth of ovarian follicles and proliferation of cumulus cells through the induction of mitosis in cells and granulosa and theca expression of genes linked to follicular maturation. Thus, seeking greater understanding of the action of these growth factors on the development of oocytes, the role of GDF9 and BMP15 in ovarian function is summarized in this brief review. PMID:26954112

  4. Granulosa cell proliferation differentiation and its role in follicular development

    Institute of Scientific and Technical Information of China (English)

    LU Cuiling; YANG Wei; HU Zhaoyuan; LIU Yixun

    2005-01-01

    Granuiosa cells (GCs) are the most important cells in the ovary that undergo serious changes morphologically and physiologically during the processes of follicular proliferation, differentiation, ovulation, lutenization and atresia. Oocyte (OC) directs GC proliferation and differentiation, while GCs influence OC maturation. Many ovarian factors are involved in the regulation of these processes via different molecular mechanisms and signal pathways. P38MAPK can selectively regulate steroidogenesis in GCs controlled by FSH; Transcript factors LRH-1 and DAX-1 play an important role in this process; FSH induces GC prolfferation and differentiation by stimulating PCNA and StAR expression and steroidogenesis. Activated ERK1/2 signal pathway may be involved in the FSH-regulated GC proliferation and differentiation. Therefore, GC is an ideal model for studying cell proliferation, differentiation and interaction,as well as signal transduction. This review briefly summarizes the latest data in the literature, including the results achieved in our laboratory.

  5. Maternal High-Fat Diet-Induced Loss of Fetal Oocytes Is Associated with Compromised Follicle Growth in Adult Rat Offspring.

    Science.gov (United States)

    Tsoulis, Michael W; Chang, Pauline E; Moore, Caroline J; Chan, Kaitlyn A; Gohir, Wajiha; Petrik, James J; Vickers, Mark H; Connor, Kristin L; Sloboda, Deborah M

    2016-04-01

    Maternal obesity predisposes offspring to metabolic and reproductive dysfunction. We have shown previously that female rat offspring born to mothers fed a high-fat (HF) diet throughout pregnancy and lactation enter puberty early and display aberrant reproductive cyclicity. The mechanisms driving this reproductive phenotype are currently unknown thus we investigated whether changes in ovarian function were involved. Wistar rats were mated and randomized to: dams fed a control diet (CON) or dams fed a HF diet from conception until the end of lactation (HF). Ovaries were collected from fetuses at Embryonic Day (E) 20, and neonatal ovaries at Day 4 (P4), prepubertal ovaries at P27 and adult ovaries at P120. In a subset of offspring, the effects of a HF diet fed postweaning were evaluated. The present study shows that fetuses of mothers fed a HF diet had significantly fewer oocytes at E20, and in neonates, have reduced AMH signaling that may facilitate an increased number of assembled primordial follicles. Both prepubertally and in adulthood, ovaries show increased follicular atresia. As adults, offspring have reduced FSH responsiveness, low expression levels of estrogen receptor alpha (Eralpha), the oocyte-secreted factor, Gdf9, oocyte-specific RNA binding protein, Dazl, and high expression levels of the granulosa-cell derived factor, AMH, in antral follicles. Together, these data suggest that ovarian compromise in offspring born to HF-fed mothers may arise from changes already observable in the fetus and neonate and in the long term, associated with increased follicular atresia through adulthood. PMID:26962114

  6. Immunohistochemical localization of basic fibroblast growth factor in bovine ovarian follicles.

    Science.gov (United States)

    van Wezel, I L; Umapathysivam, K; Tilley, W D; Rodgers, R J

    1995-12-29

    Basic fibroblast growth factor (bFGF, FGF2) controls cell proliferation and differentiation in many organs and tissues. In the ovary, cells proliferate and differentiate during folliculogenesis and during formation of the corpus luteum. While previous studies have inferred a role for bFGF in these processes, the precise contribution of bFGF to follicular activation or recruitment has not been established. For this reason, bFGF was immunolocalized in bovine follicles, using anti-bFGF immunoglobulin specific for the 1-24-amino acid terminus of the 18-kDa peptide. Basic FGF was immunolocalized to the cytoplasm of oocytes from bovine primordial and primary follicles. Strong immunostaining was also observed in corpora lutea, the ovarian surface epithelium, and smooth muscle cells surrounding blood vessels, while substantial levels of immunostaining were also present in cells of the theca interna. In most of the healthy antral follicles examined, the three or so layers of granulosa cells which were closest to the basement membrane were also stained, with greatest levels of staining at the most basal region of each cell. Atretic antral follicles had significant and uniform levels of immunostaining throughout the theca interna and the membrana granulosa. Immunostaining as described above was reduced to background levels when the primary specific immunoglobulin was preabsorbed with a 350 molar excess of peptide comprising the NH2-terminal 24 amino acids of bFGF. Based upon our previous observations and those reported here, we propose that basic fibroblast growth factor is synthesized by immature oocytes, especially those from primordial and primary follicles, and that bFGF has a potential role in activating follicle growth via stimulation of granulosa cell proliferation and follicular basement membrane synthesis. PMID:8824888

  7. Paracrine effects of oocyte secreted factors and stem cell factor on porcine granulosa and theca cells in vitro

    Directory of Open Access Journals (Sweden)

    Webb Bob

    2003-08-01

    Full Text Available Abstract Oocyte control of granulosa and theca cell function may be mediated by several growth factors via a local feedback loop(s between these cell types. This study examined both the role of oocyte-secreted factors on granulosa and thecal cells, cultured independently and in co-culture, and the effect of stem cell factor (SCF; a granulosa cell derived peptide that appears to have multiple roles in follicle development. Granulosa and theca cells were isolated from 2–6 mm healthy follicles of mature porcine ovaries and cultured under serum-free conditions, supplemented with: 100 ng/ml LR3 IGF-1, 10 ng/ml insulin, 100 ng/ml testosterone, 0–10 ng/ml SCF, 1 ng/ml FSH (granulosa, 0.01 ng/ml LH (theca or 1 ng/ml FSH and 0.01 ng/ml LH (co-culture and with/without oocyte conditioned medium (OCM or 5 oocytes. Cells were cultured in 96 well plates for 144 h, after which viable cell numbers were determined. Medium was replaced every 48 h and spent medium analysed for steroids. Oocyte secreted factors were shown to stimulate both granulosa cell proliferation (P

  8. A retrospective study of ovarian tumours and tumour-like lesions

    International Nuclear Information System (INIS)

    Background: Ovaries are common site of non-neoplastic and neoplastic lesions. They can present from the neonatal period to post menopause. Most are functional in nature and resolve with minimal treatment. Objective of the study was to determine the nature of various ovarian lesions and to ascertain the frequency and distribution of the various non-neoplastic and neoplastic lesions. Methods: The study was a retrospective review of all cases of ovarian cancer, benign ovarian neoplasm and functional ovarian cysts received during Jan-Dec 2008 at Chughtai's Lahore Laboratory. The clinical data of the patients was obtained from their respective files. Results: A total of 498 different non-neoplastic and neoplastic lesions were seen during one calendar year 2008. Non-neoplastic cysts were more common (343, 68.87%) than neoplastic tumours (155, 31.12%). The commonest non-neoplastic cyst was luteal cyst followed by follicular cyst. Among the neoplastic tumours 78.70% were benign and 21.29% were malignant. Benign serous cysts were the commonest benign tumour followed by mature cystic teratoma and mucinous cyst. Serous cyst adenocarcinoma was the commonest malignant tumour followed closely by endometrioid carcinoma and granulosa cell tumour. Krukenberg tumour, tumour metastatic to ovaries and non-Hodgkins lymphoma was also diagnosed during this period. Malignant germ cell tumours were seen in much younger age group followed by sex cord stromal tumours. Epithelial tumours were seen in much older age group. Conclusion: The morphologic diversity of ovarian masses poses many challenges. A specific diagnosis can usually be made by evaluating routinely stained slides but sometimes immunohistochemistry is required in difficult cases. Gross features also provide useful diagnostic clues. (author)

  9. Differential expression of matrix metalloproteinases during stimulated ovarian recrudescence in Siberian hamsters (Phodopus sungorus).

    Science.gov (United States)

    Salverson, Trevor J; McMichael, Greer E; Sury, Jonathan J; Shahed, Asha; Young, Kelly A

    2008-02-01

    The matrix metalloproteinases (MMPs) are a family of extracellular matrix-cleaving enzymes involved in ovarian remodeling. In many non-tropical species, including Siberian hamsters, ovarian remodeling is necessary for the functional changes associated with seasonal reproduction. We evaluated MMPs and their endogenous inhibitors (TIMPs), during photoperiod-induced ovarian recrudescence in Siberian hamsters. Hamsters were transferred from long day (LD; 16:8) to short day (SD; 8:16) photoperiods for 14weeks, and then returned to LD for 0, 1, 2, 4, or 8weeks for collection of ovaries and plasma. Post-transfer (PT) LD exposure increased body and ovarian mass. Number of corpora lutea and antral, but not preantral follicles increased in PT groups. Plasma estradiol concentrations were lower in PT weeks 0-4, and returned to LD levels at PT week 8. No change was observed in relative MMP/TIMP mRNA levels at PT week 0 (SD week 14) as compared to LD. Photostimulation increased MMP-2 mRNA at PT week 8 as compared to PT weeks 0-1. MMP-14 mRNA expression peaked at PT weeks 1-2 as compared to LD levels, while MMP-13 expression was low during this time. TIMP-1 mRNA peaked at PT week 8 as compared to PT weeks 0-4. No changes were noted in MMP-9 and TIMP-2 mRNA expression. In general, MMP/TIMP protein immunodetection followed the same patterns with most staining occurring in granulosa cells of follicles and corpora lutea. Our data suggest that mRNA and protein for several members of the MMP/TIMP families are expressed in Siberian hamster ovaries during recrudescence. Because of the variation observed in expression patterns, MMPs and TIMPs may be differentially involved with photostimulated return to ovarian function.

  10. [Haemoabdomen and haemothorax in a cow with metastatic granulosa cell tumor].

    Science.gov (United States)

    Trösch, L; Müller, K; Brosinski, K; Braun, U

    2015-06-01

    This case report describes the clinical, ultrasonographic, pathological and histological findings in a two-year-old Swiss Braunvieh cow with granulosa cell tumor and metastases in the abdomen and thorax. The cow was ill and had tachycardia, coughing, increased breath sounds, positive reticular foreign body tests and a tense abdominal wall. Ultrasonography revealed a massive accumulation of hypoechoic fluid in the thorax and abdomen, and abdomino- and thoracocentesis yielded red fluid indicative of abdominal and thoracic haemorrhage. Because of a poor prognosis, the cow was euthanized and examined postmortem. Multiple nodular lesions were seen in the omentum, liver, spleen and lungs. The left ovary was grossly enlarged and nodular in appearance. Histological examination of the lesions revealed granulosa cell tumour of the left ovary and metastases in the omentum, liver, spleen and lungs.

  11. Enhanced response of granulosa and theca cells from sheep carriers of the FecB mutation in vitro to gonadotropins and bone morphogenic protein-2, -4, and -6.

    Science.gov (United States)

    Campbell, B K; Souza, C J H; Skinner, A J; Webb, R; Baird, D T

    2006-04-01

    The FecB (Booroola) mutation, which leads to increased ovulation rates and multiple births in sheep, is now known to occur in the signaling domain of the bone morphogenic protein (BMP)-1B receptor. We examined the effect of the mutation on the responsiveness of granulosa (GC) and theca cells (TC) to BMPs and other local regulators using tissue from animals with (Fec(B/B)) and without (Fec(+/+)) the FecB mutation. Experiments examined the effect of BMP-2, -4, and -6 (0.005-50 ng/ml), and their interaction with IGF-I (0.1-10 ng/ml LR3 analog) and gonadotropins, on the proliferation and differentiation of GCs and TCs isolated from small (<2 mm) antral follicles and maintained in serum-free culture for up to 8 d. Dose-finding studies using ovaries from wild-type sheep obtained from the abbattoir showed no difference among the different BMPs in stimulating (P < 0.001) estradiol (E2) production by GCs cultured with FSH (10 ng/ml), but there was a clear interaction (P < 0.001) with IGF-I. BMPs had no effect on GC proliferation or the sensitivity of GCs to FSH. In contrast, higher doses of BMPs (5-50 ng/ml) inhibited LH-stimulated androstenedione production by TCs, whereas lower doses (0.005-0.05 ng/ml) stimulated TC proliferation (P < 0.01). Regardless of dose of IGF-I, at the end of culture (96-192 h) hormone production by GCs (E2, inhibin A) and TCs (androstenedione) was 4- to 5-fold greater (P < 0.001) by cells from Fec(B/B), compared with Fec(+/+) ewes exposed to the same dose of gonadotropin. In the presence of low concentrations of IGF-I (0.1 ng/ml), the maximum increase in the production of E2 and inhibin A by GCs from FF ewes in response to BMPs was observed at doses that were 3- to 10-fold lower (3-10 ng/ml) than ++ (30 ng/ml; P < 0.001). Low doses of BMPs stimulated proliferation of TCs from ++ (P < 0.01) but not FF ewes. Immunohistochemistry confirmed BMP-6 protein expression in the oocyte, granulosa, and thecal layers of antral follicles from both genotypes

  12. Molecular cloning and expression analyses of porcine MAP1LC3A in the granulosa cells of normal and miniature pig

    Directory of Open Access Journals (Sweden)

    Kim Sang H

    2013-02-01

    Full Text Available Abstract Background The members of the microtubule-associated protein 1 light chain (MAP1LC family, especially those of the LC3 family (MAP1LC3A, B, C, are known to induce autophagy upon localization onto the autophagosomal membrane. In this regard, LC3 can be utilized as a marker for the formation of autophagosomes during the process of autophagy. The aims of this study are to clone porcine MAP1LC3A, and analyze the pattern of its expression in the ovarian tissues of normal and miniature pig ovary in an attempt to understand the distinct mode of apoptosis between two strains. Methods Rapid amplification of cDNA ends (RACE were used to obtain the 5′ and 3′ ends of the porcine MAP1LC3A full length cDNA. Reverse-transcriptase-PCR (RT-PCR, real-time PCR, and western blot analysis were performed to examine the expression of porcine MAP1LC3A. The localization of MAP1LC3A in the ovary was determined by In situ Hybridization and Immunohistochemical staining. Results We cloned the full-length cDNA of porcine MAP1LC3A and identified an open reading frame of 980 bp encoding 121 amino acids. Based on its homology to known mammalian proteins (98% this novel cDNA was designated as porcine MAP1LC3A and registered to the GenBank (Accession No. GU272221. We compared the expression of MAP1LC3A in the Graafian follicles of normal and miniature pigs by in situ hybridization at day 15 of the estrus cycle. While normal pigs showed a stronger expression of MAP1LC3A mRNA than miniature pigs in the theca cell area, the expression was lower in the granulosa cells. Immunofluorescence analysis of the MAP1LC3A fusion reporter protein showed the subcellular localization of porcine MAP1LC3A and ATG5 as a punctate pattern in the cytoplasm of porcine granulosa cells under stress conditions. In addition, the expressions of MAP1LC3A and ATG5 were higher in normal pigs than in miniature pigs both in the presence and absence of rapamycin. Conclusions The newly cloned porcine

  13. Effect of anabolics on bovine granulosa-luteal cell primary cultures.

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    Bartolomeo Biolatti

    2007-10-01

    Full Text Available Granulosa cell tumours are observed with increased frequency among calves slaughtered in Northern Italy. The use of illegal anabolics in breeding was taken into account as a cause of this pathology. An in vitro approach was used to detect the possible alterations of cell proliferation induced by anabolics on primary cultures of bovine granulosa-luteal cells. Cultures were treated with different concentrations of substances illegally used in cattle (17beta-estradiol, clenbuterol and boldione. Cytotoxicity was determined by means of MTT test, to exclude toxic effects induced by anabolics and to determine the highest concentration to be tested. Morphological changes were evaluated by means of routine cytology, while PCNA expression was quantified in order to estimate cell proliferation. Cytotoxic effects were revealed at the highest concentrations. The only stimulating effect on cell proliferation was detected in boldione treated cultures: after 48 h treated cells, compared to controls, showed a doubled expression of PCNA. In clenbuterol and 17beta-estradiol treated cells PCNA expression was similar to controls or even decreased. As the data suggest an alteration in cell proliferation, boldione could have a role in the early stage of pathogenesis of granulosa cell tumour in cattle.

  14. Immunogold study on lectin binding in the porcine zona pellucida and granulosa cells

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    F Parillo

    2009-06-01

    Full Text Available An ultrastructural localization of lectin receptors on the zona pellucida (ZP of porcine antral oocytes and on the granulosa cells was performed using a panel of horseradish peroxidase- labelled lectins in conjunction with antiperoxidase antibody and protein A-gold. In some cases, lectin incubation was preceded by sialidase digestion. WGA-, Con-A-, UEA-I-, RCA-I-, PNA- and SBA-reactive sites were distributed differently in the porcine ZP. Sialidase digestion increased the positivity obtained with RCA-I and it was necessary to promote PNA and SBA reactivity. These results indicated that the ZP contained N-acetylglucosamine, a-mannose, a- fucose, b-Gal-(1-4GlcNAc, b-Gal- (1-3GalNAc, b-GalNAc and sialic acid residues. We also observed the presence of vesicles in both the ooplasm and granulosa cells, showing a similar lectin binding pattern to that of the ZP, thus suggesting that the oocyte and granulosa cells are the site of synthesis of ZP glucidic determinants.

  15. BILATERAL IMMATURE OVARIAN TERATOMA

    OpenAIRE

    Vinay; Aditya Pratap; Chetan; Ramesh; Rajlaxmi Jaysing

    2014-01-01

    : Immature teratoma (IMT) is tumor composed of tissues from ectoderm, mesoderm and endoderm and is considered the second most common germ cell tumor. IMT account for 10-20% of all ovarian neoplasias in women less than 20 years of age, with peak incidence between 15 and 19 years old. IMT rarely occurs during menopause. We herein reporting a rare case in a 3 years old girl with bilateral immature ovarian teratoma which is very rare in bilateralism of tumor as well as the fac...

  16. BILATERAL IMMATURE OVARIAN TERATOMA

    Directory of Open Access Journals (Sweden)

    Vinay

    2014-10-01

    Full Text Available : Immature teratoma (IMT is tumor composed of tissues from ectoderm, mesoderm and endoderm and is considered the second most common germ cell tumor. IMT account for 10-20% of all ovarian neoplasias in women less than 20 years of age, with peak incidence between 15 and 19 years old. IMT rarely occurs during menopause. We herein reporting a rare case in a 3 years old girl with bilateral immature ovarian teratoma which is very rare in bilateralism of tumor as well as the fact that the patient age is below the average for the occurrence of these tumors.

  17. Retropancreatic Ovarian Tumor.

    Science.gov (United States)

    Acharya, Soumyo Ranjan; Dasgupta, Prosenjit; Das, Subhobroto; Halder, Sandip; Panda, Nilanjan

    2016-06-01

    Retroperitoneal mucinous cystadenomas are rare lesions (less than 50 reported) characterized by presence of ovary like stroma of unknown origin. However, germinal component of ovary has never been found in them. The pancreas occasionally gives rise to mucinous cystadenomas, but they are always intrapancreatic. We report a unique case of a rare retroperitoneal mucinous cystadenomas with presence of ovarian follicles in a 45-year-old lady who presented with an abdominal mass. This was successfully excised. Though retroperitoneal mucinous cystadenomas are rare, presence of ovarian follicle (germ cell) in them has never been reported before. PMID:27358520

  18. Homeobox A7 increases cell proliferation by up-regulation of epidermal growth factor receptor expression in human granulosa cells

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    Yanase Toshihiko

    2010-06-01

    Full Text Available Abstract Background Homeobox (HOX genes encode transcription factors, which regulate cell proliferation, differentiation, adhesion, and migration. The deregulation of HOX genes is frequently associated with human reproductive system disorders. However, knowledge regarding the role of HOX genes in human granulosa cells is limited. Methods To determine the role of HOXA7 in the regulation and associated mechanisms of cell proliferation in human granulosa cells, HOXA7 and epidermal growth factor receptor (EGFR expressions were examined in primary granulosa cells (hGCs, an immortalized human granulosa cell line, SVOG, and a granulosa tumor cell line, KGN, by real-time PCR and Western blotting. To manipulate the expression of HOXA7, the HOXA7 specific siRNA was used to knockdown HOXA7 in KGN. Conversely, HOXA7 was overexpressed in SVOG by transfection with the pcDNA3.1-HOAX7 vector. Cell proliferation was measured by the MTT assay. Results Our results show that HOXA7 and EGFR were overexpressed in KGN cells compared to hGCs and SVOG cells. Knockdown of HOXA7 in KGN cells significantly decreased cell proliferation and EGFR expression. Overexpression of HOXA7 in SVOG cells significantly promoted cell growth and EGFR expression. Moreover, the EGF-induced KGN proliferation was abrogated, and the activation of downstream signaling was diminished when HOXA7 was knocked down. Overexpression of HOXA7 in SVOG cells had an opposite effect. Conclusions Our present study reveals a novel mechanistic role for HOXA7 in modulating granulosa cell proliferation via the regulation of EGFR. This finding contributes to the knowledge of the pro-proliferation effect of HOXA7 in granulosa cell growth and differentiation.

  19. Effect of 9-cis retinoic acid (RA) on progesterone and estradiol secretion and RA receptor expression in the chicken ovarian follicles.

    Science.gov (United States)

    Pawłowska, Katarzyna; Sechman, Andrzej; Suchanek, Iwona; Grzegorzewska, Agnieszka; Rzasa, Janusz

    2008-01-01

    Several lines of evidence indicate that retinoids, derivates of vitamin A, affect reproductive function in birds, however, the mechanism of their action in the ovary is still unknown. Therefore, the present study was designed (i) to show whether in the domestic hen 9-cis retinoic acid (9-cis RA), one of the retinoids, influences steroid secretion in vitro by white and yellow chicken ovarian follicles, and (ii) to detect expression of retinoic acid RXR receptor mRNA in these follicles. The white follicles (small: 1-4 mm, medium: 4-6 mm and large 6-8 mm in diameter) and the three largest yellow preovulatory follicles (F3-F1; 25-37 mm) were isolated from the ovary 3 h before ovulation. The granulosa layer was separated from the theca layer in the preovulatory follicles, which were subsequently divided into 4 equal pieces. The isolated whole white follicles or parts of the granulosa or theca layers were incubated for 24 h at 38 degrees C in Eagle's medium in the following 4 groups: control, ovine LH (oLH; 10 ng/ml), 9-cis RA (100 ng/ml) and 9-cis RA + oLH. After incubation, the medium was collected for estradiol (E2) and progesterone (P4) determination while tissues were saved for protein assay. It was found that 9-cis RA affects steroid secretion from chicken ovarian follicles. It decreased E2 secretion from white follicles and from the theca layer of the two largest (F2 and F1) preovulatory follicles. 9-cis RA had no effect on oLH-stimulated E2 secretion by the white follicles and yellow F2 and F1 follicles, but it diminished E2 secretion by F3 follicles. As regards P4, the effect of 9-cis RA was opposite; it increased P4 secretion from the granulosa layer of all preovulatory follicles. 9-cis RA did not change oLH-stimulated P4 secretion by granulosa layers ofF3 and F2 follicles, however, it inhibited oLH-enhanced P4 secretion from the F1 granulosa layer. In a separate experiment, the presence of mRNA encoding RXR was found in the stroma and all follicles of the

  20. Expression of Peptidylarginine Deiminase Type 4 in Ovarian Tumors

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    Lin Wang, Xiaotian Chang, Guangying Yuan, Yan Zhao, Pengcheng Wang

    2010-01-01

    Full Text Available Peptidylarginine deiminase type 4 (PADI4 converts arginine residues into citrulline. The current study focused on the expression of PADI4 in various subtypes of ovary cancers, and this study investigated the effects of estrogen on PADI4 expression in SKOV-3 cells that originated from ovary tumors. We utilized immunohistochemistry, real-time PCR and western blotting to analyze the expression of PADI4 in the tumor tissues and in the cell line that were cultured with estrodial-17β. PADI4 was detected in serious cystadenocarcinoma (n=39, positivity=100%, clear cell cancer (n=7, positivity= 100%, mucinous cystadenocarcinoma (n=6, positivity=100%, dysgerminoma (n=6, positivity=100%, squamous cell tumor (n=6, positivity=100%, sibnet-ring cell carcinoma (n=6, positivity=100%, endodermal sinus tumor (n=6, positivity=100%, germ cell tumors (n=6, positivity=100% and immature teratoma (n=6, positivity=100%. However, PADI4 was either not detected or detected at low levels in granulosa cell tumor (n=6, malignant thecoma (n=6, ovarian cystadenoma (n=5 and normal ovarian tissue (n=11. For serious cystadenocarcinoma, all of the samples with high PADI4 expression belonged to the T1 and T2 stages of pTMN, whereas all of the samples that exhibited weak or moderate PADI4 expression belonged to the T3 and T4 stages. PADI4 was evenly distributed in the cytoplasm of tumor cells of serious cystadenocarcinoma that were classified as being grade II and III by histopathological scoring. However, PADI4 showed granular cellular distribution in the tumor tissues that were isolated from grade I cystadenocarcinoma. In addition, the PADI4 level was positively related with the ages of the patients that presented with serious adenocarcinoma (p=0.029. Real-time PCR and western blot analyses confirmed that PADI4 was expressed at higher levels in ovarian adenocarcinoma (n=8 compared to ovarian cystadenoma (n=5 (p< 0.05. The study also detected an increased level of PADI4 in SKOV-3

  1. Influence of triiodothyronine (T(3)) on secretion of steroids and thyroid hormone receptor expression in chicken ovarian follicles.

    Science.gov (United States)

    Sechman, A; Pawlowska, K; Rzasa, J

    2009-08-01

    The present study was designed to (1) assess the role of triiodothyronine (T(3)) with regard to in vitro steroid hormone secretion by chicken ovarian follicles; (2) determine whether T(3) influences the in vivo function of the pituitary-ovarian axis in the hen; and (3) detect expression of thyroid hormone receptor (TR) mRNA in chicken ovarian follicles. In the first experiment, laying hens were decapitated 22.5h before ovulation. White prehierarchical follicles (1-8mm) and fragments of theca and granulosa layers of the 3 largest yellow preovulatory follicles F3-F1 (22-35mm) were incubated in a medium supplemented with T(3) (0, 0.1, 1, 10, 100, or 1000ng/mL) or ovine luteinizing hormone (LH) (10ng/mL) in combination with doses of T(3) (1, 10, and 100ng/mL). Triiodothyronine decreased basal and LH-stimulated estradiol secretion by white follicles and the theca layer of all preovulatory follicles. On the other hand, it increased progesterone secretion by F2 and F1 follicles. In the second experiment, hens were injected 1h after ovulation with saline (control) or T(3) (10microg/100g body weight, intraperitoneally). Results indicated that exogenous T(3) decreased plasma concentrations of LH and estradiol and increased plasma concentrations of progesterone. In the third experiment, using reverse transcription polymerase chain reaction (RT-PCR) analysis, expression of thyroid hormone receptor (TRalpha and TRbeta0), mRNA was detected in all of the ovarian compartments. The expression of TRalpha mRNA was relatively greater in comparison with TRbeta0. There were no differences between white ovarian follicles in the expression of TRalpha and TRbeta0 mRNA. A considerably higher TRalpha and lower TRbeta0 expression was detected in the granulosa layer of preovulatory follicles in comparison with the theca layer. In conclusion, the data indicate that thyroid hormones acting via nuclear receptors are involved in regulation of the pituitary-ovarian axis and processes associated

  2. The role of mitogen-activated protein kinase in insulin and insulin-like growth factor I (IGF-I) signaling cascades for progesterone and IGF-binding protein-1 production in human granulosa cells.

    Science.gov (United States)

    Seto-Young, Donna; Zajac, Jacek; Liu, Hung-Ching; Rosenwaks, Zev; Poretsky, Leonid

    2003-07-01

    Insulin and IGF-I participate in the regulation of ovulation, steroidogenesis, and IGF-binding protein (IGFBP) production in the ovary. Insulin and IGF-I actions in the ovary are closely related. For example, insulin may amplify IGF-I action in the ovary by up-regulating type I IGF receptors and inhibiting IGFBP-1 production, thus increasing the bioavailability of IGF-I. It is hypothesized that ovarian effects of insulin in insulin-resistant states are mediated via an insulin action pathway(s) distinct from those involved in glucose transport. We previously reported that insulin-induced stimulation of progesterone and inhibition of IGFBP-1 production in the human ovary are mediated by signaling pathways that are independent of phosphatidylinositol 3-kinase, the enzyme whose activation is crucial for glucose transport. We now examined whether activation of MAPK is necessary to mediate insulin-induced or IGF-I-induced stimulation of progesterone or inhibition of IGFBP-1 production in human granulosa cells. Human granulosa cells were obtained during in vitro fertilization. Cells (0.5-1 x 10(5)) were incubated for 24 h in the presence of 0, 10, 10(2), or 10(3) ng/ml insulin or 0, 0.5, 1, 2.5, or 5 ng/ml IGF-I and in the presence or absence of 1 micro M PD98059, a specific inhibitor of ERK1/2 MAPK. The progesterone concentration in the tissue culture medium was measured by RIA (Pantex, Santa Monica, CA), and the IGFBP-1 concentration was measured by immunoradiometric assay (DSL-7800, Diagnostic Systems Laboratories, Inc., Webster, TX). MAPK activity was assessed using the MAPK IP-Kinase assay kit (Upstate Biotechnology, Inc., Lake Placid, NY). ANOVA was used to compare mean values of progesterone or IGFBP-1 concentrations. MAPK was stimulated by insulin up to 350% of the baseline value. Progesterone production in human granulosa cells was stimulated by insulin in a dose-related manner to 123% of the control value (P < 0.001), and IGFBP-1 production was inhibited to 25

  3. Serum levels of anti-Müllerian hormone as a marker of ovarian function in 926 healthy females from birth to adulthood and in 172 Turner syndrome patients

    DEFF Research Database (Denmark)

    Hagen, CP; Aksglæde, Lise; Sørensen, K;

    2010-01-01

    In adult women, anti-Müllerian hormone (AMH) is related to the ovarian follicle pool. Little is known about AMH in girls.......In adult women, anti-Müllerian hormone (AMH) is related to the ovarian follicle pool. Little is known about AMH in girls....

  4. Leptin receptor in the chicken ovary: potential involvement in ovarian dysfunction of ad libitum-fed broiler breeder hens

    Directory of Open Access Journals (Sweden)

    Collin Anne

    2004-10-01

    Full Text Available Abstract In hens, the ovarian follicles committed to ovulation are arranged in an ordered follicular hierarchy. In standard broiler breeders hens genetically selected for high growth rate the reproductive function is clearly dysfunctional. Feed restriction is needed during reproductive development to limit the formation of excessive numbers of ovarian yellow follicles arranged in multiple hierarchies. To determine whether leptin is involved in the nutritional and reproductive interactions controlling follicular hierarchy in hens, blood leptin levels and ovarian expression of the leptin receptor mRNA were determined during follicle maturation in three chicken lines; a slow growing broiler "Label" genotype without reproductive dysfunction, a fast growing "Standard" genotype fed ad libitum or restricted and a fast growing "Experimental" line with intermediate reproductive performance levels. Whereas expression of the leptin receptor mRNA did not change in the theca, it clearly decreased with follicular differentiation in the granulosa of slow growing hens. In fast growing standard hens fed ad libitum and presenting significant reproductive dysfunction, the decrease was disrupted and dramatic up-regulation of granulosa cell expression of the leptin receptor was observed. On the other hand, feed restriction decreased the overall level of expression of the leptin receptor mRNA and restored the decrease with follicular growth. The level of expression of the leptin receptor probably modulates the action of leptin on follicular differentiation. Since blood leptin and other metabolic factors were not affected by the genotype or by nutritional state, the factors involved in the regulation of leptin receptor gene expression remain to be determined. This study demonstrates the involvement of leptin in the nutritional control of reproduction in birds. Leptin action on the ovary probably controls follicular hierarchy through the regulation of steroidogenesis.

  5. Managing hereditary ovarian cancer

    NARCIS (Netherlands)

    Mourits, M. J.; de Bock, G. H.

    2009-01-01

    In this review we present an overview of recent developments in the management of hereditary ovarian cancer. Until recently, intensive screening of the ovaries was recommended to mutation carriers and their first-degree female relatives. However, since screening is not effective in detecting early-s

  6. Ovarian cavernous hemangioma.

    Science.gov (United States)

    Alvarez, M; Cerezo, L

    1986-01-01

    Vascular tumors of the female genital tract are rare, especially those of the ovary. Most cases are small lesions that are discovered incidentally. We describe a 68-year-old woman with a benign hemangioma that presented clinically as a very large ovarian mass. PMID:3753575

  7. Childhood ovarian malignancy.

    Science.gov (United States)

    Mahadik, Kalpana; Ghorpade, Kanchanmala

    2014-04-01

    Objective of this article is to appraise diagnostic aspects and treatment modalities in childhood ovarian tumor in background of available evidence. Literature search on Pubmed revealed various aspects of epidemiology, histopathological diagnosis, and treatment of pediatric ovarian tumor. 85 % of childhood tumors are germ cell tumors. The varied histopathological picture in germ cell tumors poses a diagnostic and therapeutic challenge. Immunohistochemistry and newer genetic markers like SALL4 and karyopherin-2 (KPNA2) have been helpful in differentiating ovarian yolk sac tumor from dysgerminoma, teratomas, and other pictures of hepatoid, endometrioid, clear cell carcinomatous, and adenocarcinomatous tissues with varied malignant potential. Before platinum therapy, these tumors were almost fatal in children. Fertility-conserving surgery with bleomycin, etoposide, and cisplatin has dramatically changed the survival rates in these patients. This modality gives cancer cure with healthy offspring to female patients with childhood ovarian tumor. Evidence also supports this protocol resulting in successful pregnancy rates and safety of cytotoxic drugs in children born to these patients. PMID:24757335

  8. Polycystic ovarian syndrome

    OpenAIRE

    Nina Madnani; Kaleem Khan; Phulrenu Chauhan; Girish Parmar

    2013-01-01

    Polycystic ovarian syndrome (PCOS) is a "multispeciality" disorder suspected in patients with irregular menses and clinical signs of hyperandrogenism such as acne, seborrhoea, hirsutism, irregular menses, infertility, and alopecia. Recently, PCOS has been associated with the metabolic syndrome. Patients may develop obesity, insulin resistance, acanthosis nigricans, Type 2 diabetes, dyslipidemias, hypertension, non-alcoholic liver disease, and obstructive sleep apnoea. Good clinical examinatio...

  9. National Ovarian Cancer Coalition

    Science.gov (United States)

    ... 10, 2016 TESARO, Inc., an oncology-focused biopharmaceutical company, and ENGOT, the European Network for Gynecological Oncological Trial groups, today announced the presentation ... Read More NOCC Launches NOCC CancerConnect Community Social Media Network for Women with Ovarian Cancer September ...

  10. The ameliorative effect of propolis against methoxychlor induced ovarian toxicity in rat.

    Science.gov (United States)

    El-Sharkawy, Eman E; Kames, Amany O G; Sayed, S M; Nisr, Neveen A E L; Wahba, Nahed M; Elsherif, Walaa M; Nafady, Allam M; Abdel-Hafeez, M M; Aamer, A A

    2014-12-01

    A study was designed to evaluate ameliorative effect of propolis against methoxychlor (MXC) induced ovarian toxicity in rat. The organochlorine pesticide (MXC) is a known endocrine disruptor with estrogenic, anti-estrogenic, and anti-androgenic properties. To investigate whether chronic exposure to MXC could cause ovarian dysfunction, two groups of Sprague-Dawley adult female rats were exposed to MXC alone in a dose of 200mg/kg, twice/weekly, orally or MXC dose as previous plus propolis in a dose of 200mg/l/day, in drinking water for 10 months. Another two groups of rat were given corn oil (control) or propolis. Multiple reproductive parameters, ovarian weight, serum hormone levels, ovarian oxidative status and ovarian morphology were examined. In MXC-exposed group, there is a significant decrease in body and ovarian weight vs. control. MXC decreases serum estradiol and progesterone levels. A significant increase in the levels of lipid peroxidation was obtained while a significant decrease of the total antioxidant was recorded. Ovarian histopathology showed primary, secondary and vesicular follicles displaying an atretic morphology. Increase in the ovarian surface epithelium height accompanied with vacuolated, pyknotic oocytes were obtained. The previous toxic effects were neutralized by the administration of propolis in MXC+propolis group. The present results suggest that propolis may be effective in decreasing of MXC-induced ovarian toxicity in rat.

  11. Changes in homologous and heterologous gap junction contacts during maturation-inducing hormone-dependent meiotic resumption in ovarian follicles of Atlantic croaker

    Science.gov (United States)

    Bolamba, D.; Patino, R.; Yoshizaki, G.; Thomas, P.

    2003-01-01

    Homologous (granulosa cell-granulosa cell) gap junction (GJ) contacts increase in ovarian follicles of Atlantic croaker (Micropogonias undulatus) during the early (first) stage of maturation, but their profile during the second stage [i.e., during maturation-inducing hormone (MIH)-mediated meiotic resumption] is unknown. The profile of homologous GJ contacts during the second stage of maturation in croaker follicles was examined in this study and compared to that of heterologous (granulosa cell-oocyte) GJ, for which changes have been previously documented. Follicles were incubated with human chorionic gonadotropin to induce maturational competence (first stage), and then with MIH to induce meiotic resumption. The follicles were collected for examination immediately before and after different durations of MIH exposure until the oocyte had reached the stage of germinal vesicle breakdown (GVBD; index of meiotic resumption). Ultrathin sections were observed by transmission electron microscopy, and homologous and heterologous GJ contacts were quantified along a 100-??m segment of granulosa cell-zona radiata complex per follicle (three follicles/time/fish, n=3 fish). Relatively high numbers of both types of GJ were observed before and after the first few hours of MIH exposure (up to the stage of oil droplet coalescence). GJ numbers declined during partial yolk globule coalescence (at or near GVBD) and were just under 50% of starting values after the completion of GVBD (Pobservations that GVBD temporally correlates with declining heterologous GJ contacts, and for the first time in teleosts show that there is a parallel decline in homologous GJ. The significance of the changes in homologous and heterologous GJ is uncertain and deserves further study. ?? 2003 Elsevier Science (USA). All rights reserved.

  12. Granulosa cell tumors of the ovary : The clinical value of serum inhibin A and B levels in a large single center cohort

    NARCIS (Netherlands)

    Mom, C. H.; Engelen, M. J. A.; Willemse, P. H. B.; Gietema, J. A.; ten Hoor, K. A.; de Vries, E. G. E.; van der Zee, A. G. J.

    2007-01-01

    Objectives. In patients with a granulosa cell tumor of the ovary, the value of serum inhibin A and B concentrations for the assessment of disease status was investigated. Methods. In 30 consecutive patients with a stage I-III granulosa cell tumor, inhibin A and B concentrations were measured in pre-

  13. Morphological and Hormonal Identiifcation of Porcine Atretic Follicles and Relationship Analysis of Hormone Receptor Levels During Granulosa Cell Apoptosis In vivo

    Institute of Scientific and Technical Information of China (English)

    YU De-bing; YU Min-li; LIN Fei; JIANG Bao-chun; YANG Li-na; WANG Si-yu; ZHAO Ying; WNAG Zheng-chao

    2014-01-01

    Recent reports have demonstrated that follicular atresia is initiated or caused by granulosa cell apoptosis followed by theca cell degeneration in mammalian ovaries, but the mechanism of follicular atresia is still to be elucidated. Therefore, our present study was designed to examine our hypothesis that the changes of follicular microenvironment induce the granulosa cell apoptosis during pocrine follicular atresia in vivo. We ifrstly isolated intact porcine antral follicles and identiifed them into three groups, healthy follicles (HF), early atretic follicles (EAF) and progressed atretic follicles (PAF) through morphology and histology. To further conifrm their status, we detected hormone levels in follicular lfuids and the expression level of apoptosis gene Bax in granulosa cells. The rate of progesterone (P) and estradiol (E2) was increased with the expression of Bax, indicating hormone can be used as a marker of granulosa cell apoptosis or follicular atresia. Finally, we analyzed the expression level of hormone receptor genes in granulosa cells and their relationship with follicular atresia. In PAF, the expression of Progesterone receptor (PGR) was increased signiifcantly while estradiol receptor (ER) had no notable changes, which suggesting the increased-PGR accelerated the effect of P-stimulated granulosa cell apoptosis. The dramatic increasing of androgen receptor (AR) expression in PAF and the obvious increase of tumor necrosis factor-αreceptor (TNFR) in EAF indicated that there are different pathways regulating granulosa cell apoptosis during follicular atresia. Together, our results suggested that different pathways of granulosa cell apoptosis was induced by changing the follicular microenvironment during follicular atresia.

  14. Ovarian tissue cryopreservation: promises and uncertainties.

    Science.gov (United States)

    Olsthoorn-Heim, Els; de Wert, Guido

    2009-06-01

    Cancer in children and young adults is increasingly being cured by operations, radiotherapy and/or chemotherapy. However, one of the serious side effects of these treatments is the risk of damage to fertility. Whereas the most important goal used to be survival, now increasing attention is being paid to the quality of life in the long term, thanks to the success of these treatments. Infertility affects the quality of life. In post-pubescent boys and men semen can be frozen for later use prior to treatment that harms the spermatogenesis. In girls and young women the solution for reduced fertility or infertility after ovary damaging treatment, may consist of the cryopreservation of ovarian tissue prior to this treatment. At a later stage a decision can be made to transplant this ovarian tissue into the patient or to follow an IVF procedure. There are important normative questions regarding this experimental treatment. The main question is, whether it may be introduced in health care as a regular treatment or should be subject to medical research first. In the Netherlands, a working party of both doctors and ethical, legal and psychological experts recommended to carry out proper research before introducing ovarian tissue cryopreservation in regular health care. This article is meant to elucidate this policy and, including some relevant updates, thus to contribute to the discussion on this question in other European countries. PMID:19544925

  15. Premature ovarian failure and fertility in long-term survivors of Hodgkin's lymphoma: a European Organisation for Research and Treatment of Cancer Lymphoma Group and Groupe d'Etude des Lymphomes de l'Adulte Cohort Study.

    NARCIS (Netherlands)

    Kaaij, M.A. van der; Heutte, N.; Meijnders, P.; Abeilard-Lemoisson, E.; Spina, M.; Moser, E.C.; Allgeier, A.; Meulemans, B.; Simons, A.H.; Lugtenburg, P.J.; Aleman, B.M.; Noordijk, E.M.; Ferme, C.; Thomas, J.; Stamatoullas, A.; Fruchart, C.; Brice, P.; Gaillard, I.; Bologna, S.; Ong, F.; Eghbali, H.; Doorduijn, J.K.; Morschhauser, F.; Sebban, C.; Roesink, J.M.; Bouteloup, M.; Hoof, A. van; Raemaekers, J.M.M.; Henry-Amar, M.; Kluin-Nelemans, H.C.

    2012-01-01

    PURPOSE: In this large cohort of Hodgkin's lymphoma survivors with long follow-up, we estimated the impact of treatment regimens on premature ovarian failure (POF) occurrence and motherhood, including safety of nonalkylating chemotherapy and dose-response relationships for alkylating chemotherapy an

  16. Premature Ovarian Failure and Fertility in Long-Term Survivors of Hodgkin's Lymphoma : A European Organisation for Research and Treatment of Cancer Lymphoma Group and Groupe d'Etude des Lymphomes de l'Adulte Cohort Study

    NARCIS (Netherlands)

    van der Kaaij, Marleen A. E.; Heutte, Natacha; Meijnders, Paul; Abeilard-Lemoisson, Edwige; Spina, Michele; Moser, Elizabeth C.; Allgeier, Anouk; Meulemans, Bart; Simons, Arnold H. M.; Lugtenburg, Pieternella J.; Aleman, Berthe M. P.; Noordijk, Evert M.; Ferme, Christophe; Thomas, Jose; Stamatoullas, Aspasia; Fruchart, Christophe; Brice, Pauline; Gaillard, Isabelle; Bologna, Serge; Ong, Francisca; Eghbali, Houchingue; Doorduijn, Jeanette K.; Morschhauser, Franck; Sebban, Catherine; Roesink, Judith M.; Bouteloup, Marie; Van Hoof, Achiel; Raemaekers, John M. M.; Henry-Amar, Michel; Kluin-Nelemans, Hanneke C.

    2012-01-01

    Purpose In this large cohort of Hodgkin's lymphoma survivors with long follow-up, we estimated the impact of treatment regimens on premature ovarian failure (POF) occurrence and motherhood, including safety of nonalkylating chemotherapy and dose-response relationships for alkylating chemotherapy and

  17. Premature ovarian failure and fertility in long-term survivors of Hodgkin's lymphoma: A European Organisation for Research and Treatment of Cancer Lymphoma Group and Groupe d'ÉTude des Lymphomes de l'Adulte Cohort Study

    NARCIS (Netherlands)

    M.A.E. van der Kaaij (Marleen A.); N. Heutte (Natacha); P. Meijnders (Paul); E. Abeilard-Lemoisson (Edwige); M. Spina (Michele); E.C. Moser (E.); A. Allgeier (Anouk); B. Meulemans (Bart); A.H.M. Simons; P.J. Lugtenburg (Pieternella); B.M.P. Aleman (Berthe); E.M. Noordijk (Evert); C. Fermé (Christophe); J. Thomas (Jose); A. Stamatoullas (Aspasia); C. Fruchart (Christophe); P. Brice (Pauline); I. Gaillard (Isabelle); S. Bologna (Serge); F. Ong (Francisca); H. Eghbali (Houchingue); J.K. Doorduijn (Jeanette); F. Morschhauser; C. Sebban (Catherine); J.M. Roesink (Judith); M. Bouteloup (Marie); A.L. van Hoof (Achiel); J. Raemaekers; M. Henry-Amar (Michel); H.C. Kluin-Nelemans (Hanneke)

    2012-01-01

    textabstractPurpose: In this large cohort of Hodgkin's lymphoma survivors with long follow-up, we estimated the impact of treatment regimens on premature ovarian failure (POF) occurrence and motherhood, including safety of nonalkylating chemotherapy and dose-response relationships for alkylating che

  18. Natural mixtures of persistent organic pollutants (POPs) suppress ovarian follicle development, liver vitellogenin immunostaining and hepatocyte proliferation in female zebrafish (Danio rerio)

    Energy Technology Data Exchange (ETDEWEB)

    Kraugerud, Marianne, E-mail: Marianne.Kraugerud@nvh.no [Dept. of Basic Sciences and Aquatic Medicine, Norwegian School of Veterinary Science, POB 8146 Dep., 0033 Oslo (Norway); Doughty, Richard William, E-mail: vetrwdoughty@yahoo.co.uk [Sundveien 22, 2015 Leirsund (Norway); Lyche, Jan L., E-mail: Jan.Lyche@nvh.no [Dept. of Food Safety and Infection Biology, Norwegian School of Veterinary Science, POB 8146 Dep., 0033 Oslo (Norway); Berg, Vidar, E-mail: Vidar.Berg@nvh.no [Dept. of Food Safety and Infection Biology, Norwegian School of Veterinary Science, POB 8146 Dep., 0033 Oslo (Norway); Tremoen, Nina H., E-mail: Nina.Hardnes@nvh.no [Dept. of Production Animal Clinical Sciences, Norwegian School of Veterinary Science, POB 8146 Dep., 0033 Oslo (Norway); Alestrom, Peter, E-mail: Peter.Alestrom@nvh.no [Dept. of Basic Sciences and Aquatic Medicine, Norwegian School of Veterinary Science, POB 8146 Dep., 0033 Oslo (Norway); Aleksandersen, Mona, E-mail: Mona.Aleksandersen@nvh.no [Dept. of Basic Sciences and Aquatic Medicine, Norwegian School of Veterinary Science, POB 8146 Dep., 0033 Oslo (Norway); Ropstad, Erik, E-mail: Erik.Ropstad@nvh.no [Dept. of Production Animal Clinical Sciences, Norwegian School of Veterinary Science, POB 8146 Dep., 0033 Oslo (Norway)

    2012-07-15

    Persistent organic pollutants such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and dichlorodiphenyltrichloroethane (DDT) are present in high concentrations in livers of burbot (Lota lota) in Lake Mjosa, Norway. In order to assess effects of such pollutants on fish gonadal morphology, female zebrafish were exposed in two generations by food to mixtures of pollutants extracted from livers of burbot from Lake Mjosa (high and low dose) and Lake Losna, which represents background pollution, and compared to a control group. Ovarian follicle counts detected a significant decrease in late vitellogenic follicle stages in fish exposed to the Losna and the high concentrations of Mjosa mixtures in fish from the first generation. In addition, proliferation of granulosa cells, visualized by immunohistochemistry against proliferating cell nuclear antigen (PCNA), was decreased in all exposure groups in either early or late vitellogenic follicle stages compared to control. This was accompanied by increased apoptosis of granulosa cells. There was a decrease in proliferation of liver hepatocytes with exposure to both Mjosa mixtures. In addition, immunopositivity for vitellogenin in the liver was significantly lower in the Mjosa high group than in the control group. When analysing effects of parental exposure, fish with parents exposed to Mjosa high mixture had significantly higher numbers of perinucleolar follicles than fish with control parents. We conclude that long-term exposure of a real-life mixture of pollutants containing high- and background levels of chemicals supress ovarian follicle development, liver vitellogenin immunostaining intensity and hepatocyte proliferation in the zebrafish model.

  19. Gemcitabine Hydrochloride With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Recurrent Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

    Science.gov (United States)

    2016-09-19

    Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Cystadenocarcinoma; Ovarian Seromucinous Carcinoma; Ovarian Serous Cystadenocarcinoma; Ovarian Serous Surface Papillary Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Ovarian Carcinoma

  20. Ovarian pregnancy: an unusual presentation

    Directory of Open Access Journals (Sweden)

    Ayesha Arif Hussain

    2016-08-01

    Full Text Available Ovarian pregnancy is a rare type of ectopic pregnancy and usually, it ends with rupture before the end of the first trimester. The clinical picture generally mimics that of ruptured tubal ectopic pregnancy and hemorrhagic ovarian cyst. Transvaginal sonography may be helpful. We report a rare primary ruptured ovarian pregnancy in a 23 years lady. [Int J Reprod Contracept Obstet Gynecol 2016; 5(8.000: 2888-2890

  1. Novel methods of treating ovarian infertility in older and POF women, testicular infertility, and other human functional diseases.

    Science.gov (United States)

    Bukovsky, Antonin

    2015-02-25

    In vitro maturation (IVM) and in vitro fertilization (IVF) technologies are facing with growing demands of older women to conceive. Although ovarian stem cells (OSCs) of older women are capable of producing in vitro fresh oocyte-like cells (OLCs), such cells cannot respond to IVM and IVF due to the lack of granulosa cells required for their maturation. Follicular renewal is also dependent on support of circulating blood mononuclear cells. They induce intermediary stages of meiosis (metaphase I chromosomal duplication and crossover, anaphase, telophase, and cytokinesis) in newly emerging ovarian germ cells, as for the first time demonstrated here, induce formation of granulosa cells, and stimulate follicular growth and development. A pretreatment of OSC culture with mononuclear cells collected from blood of a young healthy fertile woman may cause differentiation of bipotential OSCs into both developing germ and granulosa cells. A small blood volume replacement may enable treatment of ovarian infertility in vivo. The transferred mononuclear cells may temporarily rejuvenate virtually all tissues, including improvement of the function of endocrine tissues. Formation of new follicles and their development may be sufficient for IVM and IVF. The novel proposed in vitro approaches may be used as a second possibility. Infertility of human males affects almost a half of the infertility cases worldwide. Small blood volume replacement from young healthy fertile men may also be easy approach for the improvement of sperm quality in older or other affected men. In addition, body rejuvenation by small blood volume replacement from young healthy individuals of the same sex could represent a decline of in vitro methodology in favor of in vivo treatment for human functional diseases. Here we propose for the first time that blood mononuclear cells are essential for rejuvenation of those tissues, where immune system components participate in an appropriate division and differentiation

  2. Study of the potential effect of selenium on gamma-radiation induced ovarian failure

    International Nuclear Information System (INIS)

    Radiotherapy is a major factor contributing to female infertility by inducing premature ovarian failure (POF). Therefore, the need for an effective radioprotective agent is evident. The present study investigated the mechanism of potential radioprotective effect of sodium selenite on radiation-induced ovarian failure and whether sodium selenite can stimulate in vivo follicular development in experimental rats. Immature female Sprague-Dawely rats were either exposed to gamma radiation (3.2 Gy, LD20), once and/or treated with sodium selenite (0.5 mg/kg), once daily for one week before irradiation. Follicular and oocyte development, apoptotic markers, proliferation marker as well as oxidative stress markers were assessed 24-h after irradiation. In addition, fertility assessment was performed after female rats became completely mature at two months of age. Sodium selenite significantly enhanced follicular development as compared to the irradiated group. Sodium selenite significantly reversed the oxidative stress effects of radiation that was evidenced by increasing in lipid peroxide level and decreasing in glutathione level, and glutathione peroxidase (GPx) activity. Assessment of apoptosis and cell proliferation markers revealed that caspase 3 and cytochrome c expressions markedly-increased, whereas, PCNA expression markedly-decreased in the irradiated group; in contrast, sodium selenite treatment prevented these alterations. Histopathological examination further confirmed the radioprotective efficacy of sodium selenite and its in-vivo effect on ovarian follicles’ maturation. In conclusion, sodium selenite showed a radioprotective effect and improved folliculogenesis through increasing ovarian granulosa cells proliferation, estradiol and FSH secretion, and GPx activity, whilst decreasing lipid peroxidation and oxidative stress, leading to inhibition of the apoptosis pathway through decreasing the expressions of caspase 3 and cytochrome c.

  3. Poor ovarian reserve

    Directory of Open Access Journals (Sweden)

    Padma Rekha Jirge

    2016-01-01

    Full Text Available Poor ovarian reserve (POR is an important limiting factor for the success of any treatment modality for infertility. It indicates a reduction in quantity and quality of oocytes in women of reproductive age group. It may be age related as seen in advanced years of reproductive life or may occur in young women due to diverse etiological factors. Evaluating ovarian reserve and individualizing the therapeutic strategies are very important for optimizing the success rate. Majority or women with POR need to undergo in vitro fertilization to achieve pregnancy. However, pregnancy rate remains low despite a plethora of interventions and is associated with high pregnancy loss. Early detection and active management are essential to minimize the need for egg donation in these women.

  4. Tubo-ovarian actinomycosis.

    OpenAIRE

    Shroff C; Deodhar K; Patkar V; Fonseca J

    1981-01-01

    Actinomycotic infection of the female genital tract is rare. Actinomycosis is a chronic suppurative granulomatous infection that is characterized by formation of abscesses, multiple draining sinuses and appearance of tangled mycelial masses or granules in the discharges and tissue sections. 2 cases of tubo-ovarian actinomycosis are reported. The 1st case presented clinical with gastrointestinal symptoms and a ventral scar hernia following an operation for a non-healing abdominal wound 6 mo...

  5. Spontaneous transformation of human granulosa cell tumours into an aggressive phenotype: a metastasis model cell line

    International Nuclear Information System (INIS)

    Granulosa cell tumours (GCTs) are frequently seen in menopausal women and are relatively indolent. Although the physiological properties of normal granulosa cells have been studied extensively, little is known about the molecular mechanism of GCT progression. Here, we characterise the unique behavioural properties of a granulosa tumour cell line, KGN cells, for the molecular analysis of GCT progression. Population doubling was carried out to examine the proliferation capacity of KGN cells. Moreover, the invasive capacity of these cells was determined using the in vitro invasion assay. The expression level of tumour markers in KGN cells at different passages was then determined by Western blot analysis. Finally, the growth and metastasis of KGN cells injected subcutaneously (s.c.) into nude mice was observed 3 months after injection. During in vitro culture, the advanced passage KGN cells grew 2-fold faster than the early passage cells, as determined by the population doubling assay. Moreover, we found that the advanced passage cells were 2-fold more invasive than the early passage cells. The expression pattern of tumour markers, such as p53, osteopontin, BAX and BAG-1, supported the notion that with passage, KGN cells became more aggressive. Strikingly, KGN cells at both early and advanced passages metastasized to the bowel when injected s.c. into nude mice. In addition, more tumour nodules were formed when the advanced passage cells were implanted. KGN cells cultured in vitro acquire an aggressive phenotype, which was confirmed by the analysis of cellular activities and the expression of biomarkers. Interestingly, KGN cells injected s.c. are metastatic with nodule formation occurring mostly in the bowel. Thus, this cell line is a good model for analysing GCT progression and the mechanism of metastasis in vivo

  6. MDR1 overexpression inhibits chemotherapy-induced toxicity of granulosa cells

    Science.gov (United States)

    Salih, Sana M

    2011-01-01

    OBJECTIVE To protect granulosa cells from chemotherapy-induced toxicity by retrovirus-mediated multidrug resistance gene (MDR1) transfection. DESIGN Laboratory study. SETTING Academic research laboratory in a university hospital. INTERVENTION(S) KK15 immortalized murine granulosa cell line was transiently transduced with sf91m3 retrovirus vector carrying MDR1 cDNA that encodes P-glycoprtoein (P-gp). Transduced cells were selected with colchicine and treated with doxorubicin or paclitaxel for 24–72 hours. The expression and function of MDR1 and the mRNA expression of selected steroidogenesis enzymes were evaluated by flow cytometry, cell viability assays, Western blot, and RT-PCR. MAIN OUTCOME MEASURE(S) Viability of sf91m3-transduced KK15 cells after treatment with doxorubicin and paclitaxel. RESULT(S) sf91m3-transduced KK15 demonstrated high expression of biologically active MDR1 as shown by flow cytometry analysis and immunoblotting using P-gp monoclonal antibody and Rhodamine 123 efflux assays. sf91m3-transduced KK15 exhibited significant resistance to toxicity of 10uM paclitaxel(p≤0.001). MDR1-transduced KK15 cells were also protected from doxorubicin toxicity (10nM to 2.5uM) as shown by cell viability assay (p≤0.02). Both flow cytometry and cell viability assay showed that the protection of KK15 from doxorubicin toxicity was lost at 5 uM of doxorubicin; equivalent to 500 times LD50 (p≥0.05). sf91m3-transduced KK15 showed normal mRNA expression of a panel of selected steroidogenesis enzymes. CONCLUSION(S) Retroviral gene delivery of human MDR1 inhibited chemotherapy- induced granulosa cell toxicity and offered chemoprotection in an in vitro model. PMID:21316663

  7. In vitro culture of oocytes and granulosa cells collected from normal, obese, emaciated and metabolically stressed ewes.

    Science.gov (United States)

    Tripathi, S K; Farman, M; Nandi, S; Mondal, S; Gupta, Psp; Kumar, V Girish

    2016-07-01

    The present study was undertaken to investigate the oocyte morphology, its fertilizing capacity and granulosa cell functions in ewes (obese, normal, metabolic stressed and emaciated). Ewes (Ovis aries) of approximately 3 years of age (Bellary breed) from a local village were screened, chosen and categorized into a) normal b) obese but not metabolically stressed, c) Emaciated but not metabolically stressed d) Metabolically stressed based on body condition scoring and blood markers. Oocytes and granulosa cells were collected from ovaries of the ewes of all categories after slaughter and were classified into good (oocytes with more than three layers of cumulus cells and homogenous ooplasm), fair (oocytes one or two layers of cumulus cells and homogenous ooplasm) and poor (denuded oocytes or with dark ooplasm). The good and fair quality oocytes were in vitro matured and cultured with fresh semen present and the fertilization, cleavage and blastocyst development were observed. The granulosa cells were cultured for evaluation of metabolic activity by use of the MTT assay, and cell viability, cell number as well as estrogen and progesterone production were assessed. It was observed that the good and fair quality oocytes had greater metabolic activity when collected from normal and obese ewes compared with those from emaciated and metabolically stressed ewes. No significant difference was observed in oocyte quality and maturation amongst the oocytes collected from normal and obese ewes. The cleavage and blastocyst production rates were different for the various body condition classifications and when ranked were: normal>obese>metabolically stressed>emaciated. Lesser metabolic activity was observed in granulosa cells obtained from ovaries of emaciated ewes. However, no changes were observed in viability and cell number of granulosa cells obtained from ewes with the different body condition categories. Estrogen and progesterone production from cultured granulosa cells were

  8. Tubo-ovarian actinomycosis.

    Directory of Open Access Journals (Sweden)

    Shroff C

    1981-01-01

    Full Text Available Actinomycotic infection of the female genital tract is rare. Actinomycosis is a chronic suppurative granulomatous infection that is characterized by formation of abscesses, multiple draining sinuses and appearance of tangled mycelial masses or granules in the discharges and tissue sections. 2 cases of tubo-ovarian actinomycosis are reported. The 1st case presented clinical with gastrointestinal symptoms and a ventral scar hernia following an operation for a non-healing abdominal wound 6 months earlier. The 2nd case sought medical attention for backache and leucorrhea of 4 years′ duration. Exploratory laparotomy in the 1st case revealed tubo-ovarian masses; the vermiform appendix was not traceable. The uterine cavity in the 2nd case harbored a wooden stick. Direct extension from established ileocacal actinomycosis was believed to involve the female genital adnexae in the past. Association of tubo-ovarian actinomycosis with the presence of a foreign body in the female genital tract has been reported sporadically in the literature, yet an increase in the incidence may be expected because of the frequent use of intrauterine contraceptive devices in recent times. It is suggested that in women presenting clinically with vague abdominal symptoms, backache and discharge, actinomycosis should be considered and ruled out with the help of cytologic and proper microbial culture methods. Once the diagnosis is established, the infection can be treated with good results with penicillin.

  9. Research on toxic effect of pesticide residues from schisandra on ovarian granulose cells%五味子中残留农药对卵巢颗粒细胞的毒性研究

    Institute of Scientific and Technical Information of China (English)

    姜丹丹; 朗朗; 季宇彬

    2014-01-01

    The research method of the pesticide residues toxic effect from schisandra on the o-varian granulose cell was explored .MTT assay was used to determine pesticide extract on o-varian granulosa cells after 24, 48,72 h cell proliferation,and Western blot was used to de-tect the impact of pesticide extract on the expression levels of ERK 1/2 and p-ERK1/2 pro-tein of MAPK signal pathway of ovarian granulosa cell .MTT results showed that pesticide ex-tract could significantly promote cell proliferation , and the highest growth rate was at 48 h ( P <0.01 ) .Western blot showed that pesticide extract could promote the expression of ERK1/2 and p-ERK1/2 protein , which compared with the negative control group had sig-nificant difference ( P <0 .01 ) .Therefore pesticides extract on ovarian granulosa cells in vitro could significantly promote cell proliferation by promoting the expression of ERK 1/2 , p-ERK1/2 protein of MAPK signal pathway to produce toxic effects for granulosa cells .%探讨五味子中残留农药对卵巢颗粒细胞的毒性作用.MTT 法测定农药提取物作用于卵巢颗粒细胞24、48、72 h后的细胞增殖情况;Western blot法检测农药提取物对卵巢颗粒细胞MAPK信号通路的ERK1/2及p-ERK1/2蛋白表达水平的影响.MTT结果显示农药提取物能够显著促进卵巢颗粒细胞增殖,48 h增殖率最高(P<0.01),Western blot 结果显示提取物能够促进ERK1/2、p-ERK1/2蛋白表达,与阴性对照组相比差异极显著( P<0.01).因此农药提取物作用于体外培养的卵巢颗粒细胞能够显著促进细胞增殖,通过促进MAPK信号通路的ERK1/2、p-ERK1/2蛋白表达,对颗粒细胞产生毒性作用.

  10. Expression and histopathological correlation of CCR9 and CCL25 in ovarian cancer.

    Science.gov (United States)

    Singh, Rajesh; Stockard, Cecil R; Grizzle, William E; Lillard, James W; Singh, Shailesh

    2011-08-01

    Ovarian carcinoma is the most lethal gynecological malignancy among women and its poor prognosis is mainly due to metastasis. Chemokine receptor CCR9 is primarily expressed by a small subset of immune cells. The interactions between CCL25 and CCR9 have been implicated in leukocyte trafficking to the small bowel, a frequent metastatic site for ovarian cancer cells. We have previously shown that ovarian cancer cells express CCR9 and play an important role in cell migration, invasion and survival in the presence of its natural ligand in vitro. In this study, we have evaluated the expression of CCR9 and CCL25 in ovarian cancer cells and clinical samples. Ovarian cancer tissue microarrays from University of Alabama at Birmingham and AccuMax were stained for CCR9 and CCL25. Aperio ScanScope was used to acquire 80X digital images and expression analysis of CCR9 and CCL25. Flow cytometry and the Image stream system were used to conform the expression of CCR9 and CCL25 in ovarian cancer cells. Our results show significantly higher (ptumor, dysgerminoma, transitional cell carcinoma, Brenner tumor, yolk sac tumor, adenocarcinoma and fibroma cases, compared to non-neoplastic ovarian tissue. Similar to tissue expression, CCR9 was also significantly expressed by the ovarian cancer cell lines (OVCAR-3 and SK-OV-3) in comparison to normal adult ovarian epithelial cell. We provide the first evidence that CCR9 and its natural ligand CCL25 are highly expressed by ovarian cancer tissue and their expression correlates with histological subtypes. Expression of this chemokine receptor and its ligand CCL25 within primary tumor tissue further suggests a potential role of this chemokine-receptor axis in ovarian cancer progression. PMID:21637913

  11. Clinicopathologic Analysis of Ovary Guvenile Granulosa Cell Tumor%卵巢幼年型粒层细胞瘤临床病理观察

    Institute of Scientific and Technical Information of China (English)

    崔华娟; 赖日权; 王卓才; 王炜; 彭大云

    2012-01-01

    abdomen three years after spealbone chondrosarcoma surgery and diagnosed as JGCT at stage FIGOm after the surgery. The patient died 26 months after surgery. Another case presented with hormonal disturbance and diagnosed as JGCT at stage FIGO I A, and followed up for 29 months without tumor recurrence. Microscopic examination showed diffused atypical follicular structures formed by granulosa cells. The granulosa cells contained round hyper-chromatic nuclei without nuclear grooves or Call-Exner body formation. The first case had severe cellular atypia and the mitotic count was more than 10/10 HPF. The second case had mild cellular atypia and the mitotic count was less than 5/ 10 HPF. Immunohistochemical study showed diffused positivity for vimentin (2/2) and dispersive positivity for CD99. The first case was positive for mucus carmine red stain. The second case was nodal staining for crinhibin and CK18. cytokeratin pan (CKpan), S-100 protein, protein gene product (PGP) 9.5, smooth muscle actin (SMA), epithelial membrane antigen (EMA), desmin, myogenin, vascular endothelial growth factor (VEGF), placental alkaline phosphatase (PLAP) , human chorionicgonagotropin( HCG) , alpha - fetoprotein ( AFP) , CD4 5 and Calretinin were all negative. Conclusion JGCT is a low-grade malignant tumor, but few cases are highly malignant. Early diagnose is the most important prognostic factor. JGCT should be differentiated from adult granulosa cell tumor, hypercalcemia small cell carcinoma and malignant melanoma.

  12. Imunotherapy opportunities in ovarian cancer

    Directory of Open Access Journals (Sweden)

    I. Zh. Shubina

    2013-01-01

    Full Text Available In the last decade, accumulated evidence in favor of that ovarian cancer is an immunogenic tumor. Immunotherapy is aimed at stimulating the innate and adaptive immunity, may cause an effective response in patients with ovarian cancer. Various approaches immunotherapy include cytokinetherapy, use of monoclonal antibodies and cell therapy.

  13. Cryobanking of human ovarian tissue

    DEFF Research Database (Denmark)

    Macklon, Kirsten Tryde; Ernst, Erik; Andersen, Anders Nyboe;

    2014-01-01

    Cryopreservation of ovarian tissue is one way of preserving fertility in young women with a malignant disease or other disorders that require gonadotoxic treatment. The purpose of the study was to explore how many women remained interested in continued cryostorage of their ovarian tissue beyond a...

  14. Rhesus monkey cumulus cells revert to a mural granulosa cell state after an ovulatory stimulus.

    Science.gov (United States)

    Chaffin, Charles L; Lee, Young S; VandeVoort, Catherine A; Patel, Bela G; Latham, Keith E

    2012-11-01

    Follicular somatic cells (mural granulosa cells and cumulus cells) and the oocyte communicate through paracrine interactions and through direct gap junctions between oocyte and cumulus cells. Considering that mural and cumulus cells arise through a common developmental pathway and that their differentiation is essential to reproductive success, understanding how these cells differ is a key aspect to understanding their critical functions. Changes in global gene expression before and after an ovulatory stimulus were compared between cumulus and mural granulosa cells to test the hypothesis that mural and cumulus cells are highly differentiated at the time of an ovulatory stimulus and further differentiate during the periovulatory interval. The transcriptomes of the two cell types were markedly different (>1500 genes) before an ovulatory hCG bolus but converged after ovulation to become completely overlapping. The predominant transition was for the cumulus cells to become more like mural cells after hCG. This indicates that the differentiated phenotype of the cumulus cell is not stable and irreversibly established but may rather be an ongoing physiological response to the oocyte.

  15. Dehydration hardly slows hopping toads (Rhinella granulosa) from xeric and mesic environments.

    Science.gov (United States)

    Prates, Ivan; Angilleta, Michael J; Wilson, Robbie S; Niehaus, Amanda C; Navas, Carlos A

    2013-01-01

    The locomotor capacity of amphibians depends strongly on temperature and hydration. Understanding the potential interactions between these variables remains an important challenge because temperature and water availability covary strongly in natural environments. We explored the effects of temperature and hydration on the hopping speeds of Rhinella granulosa, a small toad from the semiarid Caatinga and the Atlantic Rain Forest in Brazil. We asked whether thermal and hydric states interact to determine performance and whether toads from the Caatinga differ from their conspecifics from the Atlantic Forest. Both dehydration and cooling impaired hopping speed, but effects were independent of one another. In comparison to performances of other anurans, the performance of R. granulosa was far less sensitive to dehydration. Consequently, dehydrated members of this species may be able to sustain performance through high body temperatures, which agrees with the exceptional heat tolerance of this species. Surprisingly, toads from both the Caatinga and the Atlantic Forest were relatively insensitive to dehydration. This observation suggests that migration or gene flow between toads from the forest and those from a drier region occurred or that toads from a dry region colonized the forest secondarily. PMID:23799839

  16. Expression of Leptin Long-form Receptor mRNA in Luteinized Granulosa Cells of Obese Women with Polycystic Ovary Syndrome

    Institute of Scientific and Technical Information of China (English)

    YIN Jie; LIU Yi; LV Liqun; WANG Donghua; GONG Cheng; XIAO Wei; SHENG Hui

    2007-01-01

    To investigate the expression of mRNA of leptin long-form receptor (OB-Rb) in luteinized granulosa cells of obese women with polycystic ovary syndrome (PCOS), and to determine the role of leptin in the physiopathology of PCOS, luteinized granulosa cells were collected from the follicle fluid of 10 obese women who met the diagnostic criteria for PCOS and their BMI was equal to or greater than 25 kg/m2, and at the same time, granulosa cells were collected from 10 normal women undergoing IVF-ET who served as the control group. Some luteinized granulosa cells were taken from normal women for in-vitro culture, into which human leptin of different concentrations was added (0, 10, 100 and 1000 ng/mL). After stimulation with leptin for 48 h, RT-PCR was employed for the detection of the expression of OB-RLmRNA in the luteinized granulosa cells. Our results showed that the level of OB-RLmRNA in luteinized granulosa cells of obese PCOS women was higher than those in the control (P<0.05). In luteinized granulosa cells cultured in vitro and stimulated by human leptin for 48 h, the level of OB-RLmRNA was higher than those without leptin stimulation (P<0.01), and when leptin concentration was at 100 ng/mL, and the level of OB-RLmRNA reached a peak. It is concluded that in obese PCOS women, the level of serum leptin is increased, which promotes the expression of OB-RL in luteinized granulosa cells and increases the sensitivity of the granulosa cells to leptin. Leptin may contribute to anovulation in obese women with PCOS.

  17. Contributions of androgen and estrogen to fetal programming of ovarian dysfunction

    Directory of Open Access Journals (Sweden)

    Dumesic Daniel A

    2006-04-01

    Full Text Available Abstract In female mammals, including humans, deviations from normal androgenic or estrogenic exposure during fetal development are detrimental to subsequent adult ovarian function. Androgen deficiency, without accompanying estrogen deficit, has little apparent impact on ovarian development. Fetal estrogen deficiency, on the other hand, results in impaired oocyte and follicle development, immature and abnormal adult ovaries, and excessive ovarian stimulation from endogenous gonadotropins ultimately generating hemorrhagic follicles. Complete estrogen deficiency lasting into adulthood results in partial ovarian masculinization. Fetal androgen excess, on the other hand, mediated either by direct androgen action or following androgen aromatization to estrogen, reprograms ovarian development and reproductive neuroendocrinology to mimic that found in women with polycystic ovary syndrome: enlarged, polyfollicular, hyperandrogenic, anovulatory ovaries with accompanying LH hypersecretion. Oocyte developmental competence is also compromised. Insulin is implicated in the mechanism of both anovulation and deficient oocyte development. Fetal estrogen excess induces somewhat similar disruption of adult ovarian function to fetal androgen excess. Understanding the quality of the fetal female sex steroid hormone environment is thus becoming increasingly important in improving our knowledge of mechanisms underlying a variety of female reproductive pathologies.

  18. Transforming growth factor-β1 increases lysyl oxidase expression by downregulating MIR29A in human granulosa lutein cells.

    Science.gov (United States)

    Fang, Ying; Chang, Hsun-Ming; Cheng, Jung-Chien; Klausen, Christian; Leung, Peter C K; Yang, Xiaokui

    2016-09-01

    Lysyl oxidase (LOX), a key enzyme in the formation and stabilization of the extracellular matrix, is expressed in granulosa cells and plays a critical role in the regulation of granulosa cell differentiation, oocyte maturation and ovulation. To date, the regulation of LOX expression in human granulosa cells remains largely unknown. In this study, using primary and immortalized human granulosa lutein cells, we demonstrated that transforming growth factor (TGF)-β1 (TGFB1) upregulated LOX expression and downregulated microRNA-29a (MIR29A) expression via a TGF-β type I receptor-mediated signaling pathway. Additionally, we showed that MIR29A downregulated the expression of LOX in both types of cells. Furthermore, the downregulation of MIR29A contributed to the TGFB1-induced increase in LOX expression because the inhibition of MIR29A with a MIR29A inhibitor not only reversed the MIR29A-induced downregulation of LOX but also enhanced the TGFB1-induced upregulation of LOX. Our findings suggest that TGFB1 and MIR29A may play essential roles in the regulation of extracellular matrix remodeling during the periovulatory phase. PMID:27335131

  19. In human granulosa cells from small antral follicles, androgen receptor mRNA and androgen levels in follicular fluid correlate with FSH receptor mRNA

    DEFF Research Database (Denmark)

    Nielsen, M. E.; Rasmussen, I. A.; Kristensen, Stine Gry;

    2011-01-01

    RNA analysis (24 women). Expression of Androgen Receptor (AR) mRNA levels in granulosa cells, and of androstenedione and testosterone in FF, were correlated to the expression of FSH receptor (FSHR), LH receptor (LHR), CYP19 and anti-Müllerian Hormone-receptor2 (AMHR2) mRNA in the granulosa cells and to the FF...... with the expression of AMHR2, but did not correlate with any of the hormones in the FF. These data demonstrate an intimate association between AR expression in immature granulosa cells, and the expression of FSHR in normal small human antral follicles and between the FF levels of androgen and FSHR expression...

  20. Hydrogen-rich Water Exerting a Protective Effect on Ovarian Reserve Function in a Mouse Model of Immune Premature Ovarian Failure Induced by Zona Pellucida 3

    Science.gov (United States)

    He, Xin; Wang, Shu-Yu; Yin, Cheng-Hong; Wang, Tong; Jia, Chan-Wei; Ma, Yan-Min

    2016-01-01

    Background: Premature ovarian failure (POF) is a disease that affects female fertility but has few effective treatments. Ovarian reserve function plays an important role in female fertility. Recent studies have reported that hydrogen can protect male fertility. Therefore, we explored the potential protective effect of hydrogen-rich water on ovarian reserve function through a mouse immune POF model. Methods: To set up immune POF model, fifty female BALB/c mice were randomly divided into four groups: Control (mice consumed normal water, n = 10), hydrogen (mice consumed hydrogen-rich water, n = 10), model (mice were immunized with zona pellucida glycoprotein 3 [ZP3] and consumed normal water, n = 15), and model-hydrogen (mice were immunized with ZP3 and consumed hydrogen-rich water, n = 15) groups. After 5 weeks, mice were sacrificed. Serum anti-Müllerian hormone (AMH) levels, granulosa cell (GC) apoptotic index (AI), B-cell leukemia/lymphoma 2 (Bcl-2), and BCL2-associated X protein (Bax) expression were examined. Analyses were performed using SPSS 17.0 (SPSS Inc., Chicago, IL, USA) software. Results: Immune POF model, model group exhibited markedly reduced serum AMH levels compared with those of the control group (5.41 ± 0.91 ng/ml vs. 16.23 ± 1.97 ng/ml, P = 0.033) and the hydrogen group (19.65 ± 7.82 ng/ml, P = 0.006). The model-hydrogen group displayed significantly higher AMH concentrations compared with that of the model group (15.03 ± 2.75 ng/ml vs. 5.41 ± 0.91 ng/ml, P = 0.021). The GC AI was significantly higher in the model group (21.30 ± 1.74%) than those in the control (7.06 ± 0.27%), hydrogen (5.17 ± 0.41%), and model-hydrogen groups (11.24 ± 0.58%) (all P hydrogen group compared with that of the hydrogen group (11.24 ± 0.58% vs. 5.17 ± 0.41%, P = 0.021). Compared with those of the model group, ovarian tissue Bcl-2 levels increased (2.18 ± 0.30 vs. 3.01 ± 0.33, P = 0.045) and the Bax/Bcl-2 ratio decreased in the model-hydrogen group

  1. Analysis of computed tomography of ovarian tumor

    Energy Technology Data Exchange (ETDEWEB)

    Omura, Makoto; Taniike, Keiko; Nishiguchi, Hiroyasu

    1987-07-01

    One hundred and twenty six patients with ovarian mass were studied with computed tomography (CT) and classified into five groups according to its margin and inner structure. The incidence of malignancy of cystic ovarian mass with smooth margin was low and that of solid ovarian mass with irreglar margin was high. Three cases (6.7 %) of malignant ovarian tumor demonstrated completely cystic pattern. Ovarian teratomas contained well defined component of fat density.

  2. Plasma and ovarian oestradiol and the variability in the LH surge induced in ewes by the ram effect.

    Science.gov (United States)

    Fabre-Nys, Claude; Chanvallon, Audrey; Debus, Nathalie; François, Dominique; Bouvier, Frédéric; Dupont, Joelle; Lardic, Lionel; Lomet, Didier; Ramé, Christelle; Scaramuzzi, Rex J

    2015-05-01

    The proportion of anoestrous ewes ovulating after exposure to a sexually active ram is variable mainly due to whether an LH surge is induced. The aim of this study was to determine the role of oestradiol (E2) in the ram-induced LH surge. In one study, we measured the plasma concentrations of E2 in ewes of different breeds before and after the 'ram effect' and related these patterns to the presence and latency of the LH surge, while another compared ovarian responses with the 'ram effect' following exposure to rams for 2 or 12 h. In all ewes, the concentration of E2 increased 2-4 h after rams were introduced and remained elevated for 14.5 ± 0.86 h. The quantity of E2 secreted before the LH surge varied among breeds as did the mean concentration of E2. The granulosa cells of IF ewes collected after 12 h exposure to rams secreted more E2 and progesterone and had higher levels of StAR than the 2 h group but in MV ewes there was no differences between these groups for any of these parameters. These results demonstrate that the LH surge induced by the rams is a result of increased E2 secretion associated with increased levels of STAR in granulosa cells and that these responses varied among breeds. The results suggest that the variable occurrence of a LH surge and ovulation may be the result of variable ovarian responses to the 'ram effect' and insensitivity of the hypothalamus to the E2-positive feedback signal.

  3. BMP2, 4 and 6 and BMPR1B are altered from early stages of bovine cystic ovarian disease development.

    Science.gov (United States)

    Díaz, Pablo U; Hein, Gustavo J; Belotti, Eduardo M; Rodríguez, Fernanda M; Rey, Florencia; Amweg, Ayelén N; Matiller, Valentina; Baravalle, María E; Ortega, Hugo H; Salvetti, Natalia R

    2016-10-01

    Cystic ovarian disease (COD) is an important cause of subfertility in dairy cattle. Bone morphogenetic proteins (BMPs), mainly BMP2, BMP4 and BMP6, play a key role in female fertility. In this study, we hypothesized that an altered BMP system is associated with ovarian alterations contributing to COD pathogenesis. Therefore, we examined the expression of BMP2, BMP4 and BMP6 and BMP receptor 1B (BMPR1B) in the ovaries of animals with spontaneous or ACTH-induced COD, as well as during the development of the disease, in a model of follicular persistence induced by low doses of progesterone (at 5, 10 and 15 days of follicular persistence). Results showed changes in BMP2, BMP4 and BMP6 expression during folliculogenesis, in granulosa and theca cells in the COD groups, as well as at different stages of follicular persistence. Results also showed changes in BMPR1B expression in developing follicles in animals with COD, and at the initial stages of follicular persistence (P5). Comparison between groups showed significant differences, mainly in BMP4 and BMP6 expression, in granulosa and theca cells of different follicular categories. The expression of these BMPs also increased in cystic and persistent follicles, in relation to antral follicles of the control group. BMPR1B showed high expression in cystic follicles. Together, these results may indicate an alteration in BMPs, especially in BMP4 and BMP6, as well as in BMPR1B, which occurs early in folliculogenesis and incipiently during the development of COD, which could be a major cause of recurrence of this disease in cattle.Free Spanish abstract: A Spanish translation of this abstract is freely available at http://www.reproduction-online.org/content/early/2016/08/01/REP-15-0315/suppl/DC1. PMID:27486268

  4. Tubal ligation and salpingectomy and the risk of epithelial ovarian cancer and borderline ovarian tumors

    DEFF Research Database (Denmark)

    Madsen, C; Baandrup, Louise; Dehlendorff, Christian;

    2015-01-01

    OBJECTIVE: According to the recent theories on the ovarian cancer origin, any protective effect of tubal ligation may vary with histologic subtype of ovarian cancer. Furthermore, bilateral salpingectomy may represent an opportunity for surgical prevention of serous ovarian cancer. DESIGN: Nationw......OBJECTIVE: According to the recent theories on the ovarian cancer origin, any protective effect of tubal ligation may vary with histologic subtype of ovarian cancer. Furthermore, bilateral salpingectomy may represent an opportunity for surgical prevention of serous ovarian cancer. DESIGN...

  5. "Incessant ovulation" and ovarian cancer.

    Science.gov (United States)

    Casagrande, J T; Louie, E W; Pike, M C; Roy, S; Ross, R K; Henderson, B E

    1979-07-28

    A case-control study of 150 ovarian cancer patients under the age of 50 and individually matched controls was done to study the influence of fertility and oral contraceptive use on the risk of ovarian cancer. The risk decreased with increasing numbers of live births, with increasing numbers of incomplete pregnancies, and with the use of oral contraceptives. These three factors can be amalgamated into a single index of protection--"protected time"--by considering them all as periods of anovulation. The complement of protected time--viz., "ovulatory age", the period between menarche and diagnosis of ovarian cancer (or cessation of menses) minus "protected time"--was strongly related to risk of ovarian cancer. Other factors found to be associated with increased ovarian cancer risk were obesity, cervical polyps, and gallbladder disease. Women who had an "immediate" intolerance to oral contraceptive use had a fourfold increased risk of ovarian cancer. 7 patients, but no controls, could recall a family history of ovarian cancer. PMID:89281

  6. Premature ovarian failure.

    Science.gov (United States)

    Vujović, Svetlana; Ivović, Miomira; Tancić-Gajić, Milina; Marina, Ljiljana; Barać, Marija; Arizanović, Zorana; Nenezić, Ana; Ivanisević, Maja; Micić, Jelena; Sajić, Silvija; Micić, Dragan

    2012-01-01

    Premature ovarian failure (POF) is the occurrence of hypergonadotropic hypoestrogenic amenorrhea in women under the age of forty years. It is idiopathic in 74-90% patients. Known cases can be divided into primary and secondary POF. In primary POF genetic aberrations can involve the X chromosome (monosomy, trisomy, translocations, deletions) or autosomes. Genetic mechanisms include reduced gene dosage and non-specific chromosome effects impairing meiosis, decreasing the pool of primordial follicles and increasing atresia due to apoptosis or failure of follicle maturation. Autoimmune ovarian damage is caused by alteration of T-cell subsets and T-cell mediated injury, increase of autoantibody producing B-cells, a low number of effector/cytotoxic lymphocyte, which decreases the number and activity of natural killer cells. Bilateral oophorectomy, chemotherapy, radiotherapy and infections cause the secondary POF. Symptoms of POF include irritability, nervousness, loss of libido, depression, lack of concentration, hot flushes, weight gaining, dry skin, vaginal dryness, frequent infections etc.The diagnosis is confirmed by the level of FSH of over 40 IU/L and estradiol below 50 pmol/L in women aged below 40 years. Biochemical and other hormonal analysis (free thyroxin, TSH, prolactin, testosterone), karyotype (libido. Sequential estrogen progestagen replacement therapy is the first line therapy for ovulation induction in those looking for pregnancy and after that oocyte donation will be advised. Appropriate estro-progestagen therapy improves the quality of life and prevents complications such as cardiovascular diseases, osteoporosis, stroke etc. PMID:23350261

  7. Correlation between anti-Mullerian hormone and follicle-stimulating hormone receptor mRNA expression in granulosa cells in vitro.%体外颗粒细胞培养中抗苗勒管激素与卵泡刺激素受体mRNA表达的相关性

    Institute of Scientific and Technical Information of China (English)

    张迪; 桑丽英; 崔蓉; 苗竹林; 钟兴明; 韦相才

    2012-01-01

    目的 体外培养小鼠原代颗粒细胞培养液中,加入不同浓度的抗苗勒管激素(AMH),比较各组间小鼠颗粒细胞上卵泡刺激素受体(FSHR)mRNA的表达情况,探讨体外培养颗粒细胞中AMH与FSHRmRNA表达的关系.方法 选取4~5周的昆明雌性小鼠,腹腔注射孕马血清促性腺激素,48~54h后颈椎脱臼法处死小鼠,取双侧卵巢,采用机械分离法释放颗粒细胞,胰蛋白酶消化细胞,低速离心分离细胞,用含15%胎牛血清的DMEM/F12培养基置于37℃、5%CO2培养箱中培养.显微镜观察细胞形态,流式细胞术分离细胞,并用免疫荧光法对所培养的颗粒细胞进行鉴定.同时在体外培养的小鼠原代颗粒细胞培养液中加入不同浓度(5、10、20、30、40ng/mL)的AMH,测定每组培养基中AMH的终浓度,并用荧光定量PCR技术检测每组颗粒细胞中FSHR mRNA 的表达.结果 分离培养的颗粒细胞纯度大于80%;随AMH浓度加大,小鼠颗粒细胞中FSHR mRNA的表达逐渐降低,当AMH浓度为 5 和10ng/mL时,与对照组比较差异有统计学意义(P<0.05),且5 ng/mL浓度组颗粒细胞上FSHR mRNA的表达量最高.结论 用机械分离加胰酶消化加低速离心能得到纯度较高活性很好的颗粒细胞,用FSHR鉴定颗粒细胞是一种简便易行的方法,AMH浓度与颗粒细胞上FSHRmRNA表达呈一定负相关,表明AMH有可能通过抑制FSHR表达降低FSH敏感性,从而参与卵巢早衰的病理生理过程.%Objective To investigate the correlation between anti - Mullerian hormone (AMH) and follicle -stimulating hormone receptor (FSHR) mRNA expression in the cultured granulosa cells in vitro. Methods Kunming female mice were peritoneally injected with pregnant mare serum gonadotropin (PMSG) and sacrificed 48 to 54 hours after injection for collection of ovarian. Granulosa cells were isolated by mechanical method, trypsin digestion and low - speed centrifugation. Granulosa cells were diluted and incubated in

  8. Maternal obesity is associated with ovarian inflammation and upregulation of early growth response factor 1.

    Science.gov (United States)

    Ruebel, Meghan; Shankar, Kartik; Gaddy, Dana; Lindsey, Forrest; Badger, Thomas; Andres, Aline

    2016-07-01

    Obesity impairs reproductive functions through multiple mechanisms, possibly through disruption of ovarian function. We hypothesized that increased adiposity will lead to a proinflammatory gene signature and upregulation of Egr-1 protein in ovaries from obese (OB; n = 7) compared with lean (LN; n = 10) female Sprague-Dawley rats during the peri-implantation period at 4.5 days postcoitus (dpc). Obesity was induced by overfeeding (40% excess calories for 28 days) via total enteral nutrition prior to mating. OB dams had higher body weight (P < 0.001), greater fat mass (P < 0.001), and reduced lean mass (P < 0.05) and developed metabolic dysfunction with elevated serum lipids, insulin, leptin, and CCL2 (P < 0.05) compared with LN dams. Microarray analyses identified 284 differentially expressed genes between ovaries from LN vs. OB dams (±1.3 fold, P < 0.05). RT-qPCR confirmed a decrease in expression of glucose transporters GLUT4 and GLUT9 and elevation of proinflammatory genes, including CCL2, CXCL10, CXCL11, CCR2, CXCR1, and TNFα in ovaries from OB compared with LN (P < 0.05). Protein levels of PI3K and phosphorylated Akt were significantly decreased (P < 0.05), whereas nuclear levels of Egr-1 (P < 0.05) were increased in OB compared with LN ovaries. Moreover, Egr-1 was localized to granulosa cells, with the highest expression in cumulus cells of preovulatory follicles. mRNA expression of VCAN, AURKB, and PLAT (P < 0.05) correlated with %visceral fat weight (r = 0.51, -0.77, and -0.57, respectively, P ≤ 0.05), suggesting alterations in ovarian function with obesity. In summary, maternal obesity led to an upregulation of inflammatory genes and Egr-1 expression in peri-implantation ovarian tissue and a concurrent downregulation of GLUTs and Akt and PI3K protein levels. PMID:27279249

  9. Involvement of ERK1/2 signaling pathway in atrazine action on FSH-stimulated LHR and CYP19A1 expression in rat granulosa cells

    Energy Technology Data Exchange (ETDEWEB)

    Fa, Svetlana; Pogrmic-Majkic, Kristina; Samardzija, Dragana; Glisic, Branka; Kaisarevic, Sonja; Kovacevic, Radmila; Andric, Nebojsa, E-mail: nebojsa.andric@dbe.uns.ac.rs

    2013-07-01

    Worldwide used herbicide atrazine is linked to reproductive dysfunction in females. In this study, we investigated the effects and the mechanism of atrazine action in the ovary using a primary culture of immature granulosa cells. In granulosa cells, follicle-stimulating hormone (FSH) activates both cyclic adenosine monophosphate (cAMP) and extracellular-regulated kinase 1/2 (ERK1/2) cascades, with cAMP pathway being more important for luteinizing hormone receptor (LHR) and aromatase (CYP19A1) mRNA expression. We report that 48 h after atrazine exposure the FSH-stimulated LHR and CYP19A1 mRNA expression and estradiol synthesis were decreased, with LHR mRNA being more sensitive to atrazine than CYP19A1 mRNA. Inadequate acquisition of LHR in the FSH-stimulated and atrazine-exposed granulosa cells renders human chorionic gonadotropin (hCG) ineffective to stimulate amphiregulin (Areg), epiregulin (Ereg), and progesterone receptor (Pgr) mRNA expression, suggesting anti-ovulatory effect of atrazine. To dissect the signaling cascade involved in atrazine action in granulosa cells, we used U0126, a pharmacological inhibitor of ERK1/2. U0126 prevents atrazine-induced decrease in LHR and CYP19A1 mRNA levels and estradiol production in the FSH-stimulated granulosa cells. ERK1/2 inactivation restores the ability of hCG to induce expression of the ovulatory genes in atrazine-exposed granulosa cells. Cell-based ELISA assay revealed that atrazine does not change the FSH-stimulated ERK1/2 phosphorylation in granulosa cells. The results from this study reveal that atrazine does not affect but requires ERK1/2 phosphorylation to cause decrease in the FSH-induced LHR and CYP19A1 mRNA levels and estradiol production in immature granulosa cells, thus compromising ovulation and female fertility. - Highlights: • Atrazine inhibits estradiol production in FSH-stimulated granulosa cells. • Atrazine inhibits LHR and Cyp19a1 mRNA expression in FSH-stimulated granulosa cells. • Atrazine

  10. Genomic profile of ovarian carcinomas

    OpenAIRE

    Micci, Francesca; Haugom, Lisbeth; Vera M. Abeler; Davidson, Ben; Tropé, Claes G; Heim, Sverre

    2014-01-01

    Background It is known that all tumors studied in sufficient number to draw conclusions show characteristic/specific chromosomal rearrangements, and the identification of these chromosomes and the genes rearranged behind the aberrations may ultimately lead to a tailor-made therapy for each cancer patient. Knowledge about the acquired genomic aberrations of ovarian carcinomas is still unsatisfactory. Methods We cytogenetically analyzed 110 new cases of ovarian carcinoma of different histologic...

  11. Ultrasound in evaluating ovarian reserve

    OpenAIRE

    Eman Ahmaed Shawky Sabek; Ola I. Saleh; Howida A. Ahmed

    2015-01-01

    The objective of this study was to compare the diagnostic accuracy of transvaginal ultrasound (TVS), as a less invasive technique instead of hormonal assay to evaluate the ovarian reserve. This study included fifty-five females with breast cancer and we compared the ovarian reserve for these patients by hormonal assay through measuring the serum AntiMullerian Hormone (AMH) level and follicular stimulating hormone (FSH) level before and after chemotherapy, and by transvaginal ultrasound throug...

  12. The origin of ovarian teratomas.

    OpenAIRE

    Parrington, J M; West, L F; Povey, S

    1984-01-01

    Chromosome and enzyme markers have been studied in 21 benign ovarian teratomas from 14 patients. Markers heterozygous in the patient were completely homozygous in 52% of the teratomas and completely heterozygous in 19%. The remainder showed a mixture of the two, 10% having homozygous centromeres with some heterozygous enzyme markers and 19% having heterozygous centromeres and some homozygous enzyme markers. These results suggest that benign ovarian teratomas in the present series arise from g...

  13. Ovarian Abscess Following Therapeutic Insemination

    OpenAIRE

    Kolb, Bradford A.; Lane Mercer; Albert J. Peters; Ralph Kazer

    1994-01-01

    Background: Artificial insemination is a commonly performed procedure for the treatment of various forms of infertility. Infectious complications have only rarely been noted as a complication of intrauterine insemination (IUI). Case: In this presentation, we report the first case of an ovarian abscess following IUI with the husband's semen. Despite treatment with triple antibiotics, an oophorectomy was required. Surgical as well as pathological evaluation confirmed the diagnosis of an ovarian...

  14. Polycystic ovarian syndrome

    Directory of Open Access Journals (Sweden)

    Nina Madnani

    2013-01-01

    Full Text Available Polycystic ovarian syndrome (PCOS is a "multispeciality" disorder suspected in patients with irregular menses and clinical signs of hyperandrogenism such as acne, seborrhoea, hirsutism, irregular menses, infertility, and alopecia. Recently, PCOS has been associated with the metabolic syndrome. Patients may develop obesity, insulin resistance, acanthosis nigricans, Type 2 diabetes, dyslipidemias, hypertension, non-alcoholic liver disease, and obstructive sleep apnoea. Good clinical examination with hematological and radiological investigations is required for clinical evaluation. Management is a combined effort involving a dermatologist, endocrinologist, gynecologist, and nutritionist. Morbidity in addition includes a low "self image" and poor quality of life. Long term medications and lifestyle changes are essential for a successful outcome. This article focuses on understanding the normal and abnormal endocrine functions involved in the pathogenesis of PCOS. Proper diagnosis and management of the patient is discussed.

  15. Neonatal overfeeding induces early decline of the ovarian reserve: Implications for the role of leptin.

    Science.gov (United States)

    Sominsky, Luba; Ziko, Ilvana; Soch, Alita; Smith, Jeremy T; Spencer, Sarah J

    2016-08-15

    Early life nutrition is crucial for reproduction. Overweight and obese girls are more likely to experience early menarche, increasing the risk of adult disease. We have previously demonstrated neonatal overfeeding in the rat leads to accelerated growth, early puberty and increased circulating levels of leptin, an adipocyte-derived hormone that regulates puberty. However, the long-term consequences of accelerated puberty and metabolic dysfunction on ovarian reserve are unknown. Here we show that neonatal overfeeding reduced the number of ovarian follicles in adult rats; specifically, the primordial follicle pool was reduced compared to controls. The reduction of ovarian reserve coincided with a diminished release of pituitary gonadotropins at ovulation and altered expression of ovarian markers important for follicular recruitment and survival. These changes were associated with increased levels of ovarian leptin and its receptor. Postnatal administration of leptin antagonist did not reverse the weight gain induced by early life overfeeding, but rescued the decline in the primordial follicle pool and abolished the differences in circulating leptin and gonadotropins. Our findings suggest that the acute effects of elevated circulating leptin may be responsible for the long-term reproductive outcomes after neonatal overfeeding, leading to premature ovarian ageing and changes in reproductive efficiency. PMID:27154163

  16. Tamoxifen and ovarian function.

    Directory of Open Access Journals (Sweden)

    Martine Berliere

    Full Text Available BACKGROUND: Some studies suggest that the clinical parameter "amenorrhea" is insufficient to define the menopausal status of women treated with chemotherapy or tamoxifen. In this study, we investigated and compared the ovarian function defined either by clinical or biological parameters in pre-menopausal breast cancer patients treated with tamoxifen administered as adjuvant therapy. MATERIALS AND METHODS: Between 1999 and 2003, 138 premenopausal patients consecutively treated for early breast cancer were included. Sixty-eight received tamoxifen in monotherapy as the only adjuvant systemic treatment (Group I and 70 were treated with tamoxifen after adjuvant chemotherapy (Group II. All patients had a confirmed premenopausal status based on clinical parameters and hormonal values at study entry. They were followed prospectively every 3 months for 3 years: menses data, physical examination and blood tests (LH, FSH, 17-beta-estradiol. Vaginal ultrasonography was carried out every 6 months. After 3 years, prospective evaluation was completed and monitoring of ovarian function was performed as usual in our institution (1x/year. All data were retrospectively evaluated in 2011. RESULTS: Three patients were excluded from the study in group I and 2 were excluded in group II. Patients were divided into 4 subgroups according to clinical data, i.e. menses patterns. These patterns were assessed by questionnaires. a: Regular menses (>10 cycles/year b: Oligomenorrhea (5 to 9 cycles/year c: Severe oligomenorrhea (1 to 4 cycles/year d: Complete amenorrhea Estrogen levels did not appear to have any impact on disease-free survival rates after 3 or 8 years. FSH values were also documented and analyzed. They exhibited the same profile as estradiol values. CONCLUSIONS: Amenorrhea is an insufficient parameter to define menopausal status in patients receiving tamoxifen. Low estradiol levels must be coupled with other biological parameters to characterize endocrine status

  17. Premature ovarian failure

    Directory of Open Access Journals (Sweden)

    Vujović Svetlana

    2012-01-01

    Full Text Available Premature ovarian failure (POF is the occurrence of hypergonadotropic hypoestrogenic amenorrhea in women under the age of forty years. It is idiopathic in 74-90% patients. Known cases can be divided into primary and secondary POF. In primary POF genetic aberrations can involve the X chromosome (monosomy, trisomy, translocations, deletions or autosomes. Genetic mechanisms include reduced gene dosage and non-specific chromosome effects impairing meiosis, decreasing the pool of primordial follicles and increasing atresia due to apoptosis or failure of follicle maturation. Autoimmune ovarian damage is caused by alteration of T-cell subsets and T-cell mediated injury, increase of autoantibody producing B-cells, a low number of effector/cytotoxic lymphocyte, which decreases the number and activity of natural killer cells. Bilateral oophorectomy, chemotherapy, radiotherapy and infections cause the secondary POF. Symptoms of POF include irritability, nervousness, loss of libido, depression, lack of concentration, hot flushes, weight gaining, dry skin, vaginal dryness, frequent infections etc. The diagnosis is confirmed by the level of FSH of over 40 IU/L and estradiol below 50 pmol/L in women aged below 40 years. Biochemical and other hormonal analysis (free thyroxin, TSH, prolactin, testosterone, karyotype (<30 years of age, ultrasound of the breasts and pelvis are advisable. Optimal therapy is combined estrogen progestagen therapy given in a sequential rhythm, after excluding absolute contraindications. Testosterone can be added to adnexectomized women and those with a low libido. Sequential estrogen progestagen replacement therapy is the first line therapy for ovulation induction in those looking for pregnancy and after that oocyte donation will be advised. Appropriate estro-progestagen therapy improves the quality of life and prevents complications such as cardiovascular diseases, osteoporosis, stroke etc.

  18. Critical Role of FoxO1 in Granulosa Cell Apoptosis Caused by Oxidative Stress and Protective Effects of Grape Seed Procyanidin B2

    Directory of Open Access Journals (Sweden)

    Jia-Qing Zhang

    2016-01-01

    Full Text Available Reactive oxygen species (ROS are closely related to the follicular granulosa cell apoptosis. Grape seed procyanidin B2 (GSPB2 has been reported to possess potent antioxidant activity. However, the GSPB2-mediated protective effects and the underlying molecular mechanisms in granulosa cell apoptosis process remain unknown. In this study, we showed for the first time that GSPB2 treatment decreased FoxO1 protein level, improved granulosa cell viability, upregulated LC3-II protein level, and reduced granulosa cell apoptosis rate. Under a condition of oxidative stress, GSPB2 reversed FoxO1 nuclear localization and increased its level in cytoplasm. In addition, FoxO1 knockdown inhibited the protective effects of GSPB2 induced. Our findings suggest that FoxO1 plays a pivotal role in regulating autophagy in granulosa cells, GSPB2 exerts a potent and beneficial role in reducing granulosa cell apoptosis and inducing autophagy process, and targeting FoxO1 could be significant in fighting against oxidative stress-reduced female reproductive system diseases.

  19. Hormone therapy and ovarian cancer

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms;

    2009-01-01

    CONTEXT: Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration. OBJECTIVE: To assess risk of ovarian cancer in perimenopausal and postmenopau......CONTEXT: Studies have suggested an increased risk of ovarian cancer among women taking postmenopausal hormone therapy. Data are sparse on the differential effects of formulations, regimens, and routes of administration. OBJECTIVE: To assess risk of ovarian cancer in perimenopausal...... and postmenopausal women receiving different hormone therapies. DESIGN AND SETTING: Nationwide prospective cohort study including all Danish women aged 50 through 79 years from 1995 through 2005 through individual linkage to Danish national registers. Redeemed prescription data from the National Register...... bands included hormone exposures as time-dependent covariates. PARTICIPANTS: A total of 909,946 women without hormone-sensitive cancer or bilateral oophorectomy. MAIN OUTCOME MEASURE: Ovarian cancer. RESULTS: In an average of 8.0 years of follow-up (7.3 million women-years), 3068 incident ovarian...

  20. Doxorubicin-induced ovarian toxicity

    Directory of Open Access Journals (Sweden)

    Rizel Shulamith

    2010-03-01

    Full Text Available Abstract Background Young cancer patients may occasionally face infertility and premature gonadal failure. Apart from its direct effect on follicles and oocytes, chemotherapy may induce ovarian toxicity via an impact on the entire ovary. The role of doxorubicin in potential ovarian failure remains obscure. Our intention was to elucidate doxorubicin-related toxicity within ovaries. Methods Female mice were injected intraperitoneally with 7.5 or 10 mg/kg doxorubicin and their ovaries were visualized in vivo by high resolution MRI, one day and one month following treatment. Ovaries of other treated mice were excised and weighed at the same post-treatment intervals. Ovarian histological sections were stained for TUNEL or active caspase-3 and follicles were counted and categorized. Ovulation rates were evaluated in superovulated female mice treated with doxorubicin. Results A single injection of doxorubicin resulted in a major reduction in both ovarian size and weight that lasted even one month post treatment. A dramatic reduction in ovulation rate was observed one week after treatment, followed by a partial recovery at one month. Histological examination revealed positive staining of TUNEL and active caspase-3. We observed a significant reduction in the population of secondary and primordial follicles one month following treatment. Conclusions Our results may imply a mechanism of chemotherapy-induced ovarian toxicity, manifested by reduced ovulation and accompanied by a reduction in ovarian size, caused probably by an acute insult to the ovary.

  1. Leptin interferes with 3',5'-Cyclic Adenosine Monophosphate (cAMP signaling to inhibit steroidogenesis in human granulosa cells

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    HoYuen Basil

    2009-10-01

    Full Text Available Abstract Background Obesity has been linked to an increased risk of female infertility. Leptin, an adipocytokine which is elevated during obesity, may influence gonadal function through modulating steroidogenesis in granulosa cells. Methods The effect of leptin on progesterone production in simian virus 40 immortalized granulosa (SVOG cells was examined by Enzyme linked immunosorbent assay (ELISA. The effect of leptin on the expression of the steroidogenic enzymes (StAR, P450scc, 3betaHSD in SVOG cells was examined by real-time PCR and Western blotting. The mRNA expression of leptin receptor isoforms in SVOG cells were examined by using PCR. SVOG cells were co-treated with leptin and specific pharmacological inhibitors to identify the signaling pathways involved in leptin-reduced progesterone production. Silencing RNA against leptin receptor was used to determine that the inhibition of leptin on cAMP-induced steroidogenesis acts in a leptin receptor-dependent manner. Results and Conclusion In the present study, we investigated the cellular mechanisms underlying leptin-regulated steroidogenesis in human granulosa cells. We show that leptin inhibits 8-bromo cAMP-stimulated progesterone production in a concentration-dependent manner. Furthermore, we show that leptin inhibits expression of the cAMP-stimulated steroidogenic acute regulatory (StAR protein, the rate limiting de novo protein in progesterone synthesis. Leptin induces the activation of ERK1/2, p38 and JNK but only the ERK1/2 (PD98059 and p38 (SB203580 inhibitors attenuate the leptin-induced inhibition of cAMP-stimulated StAR protein expression and progesterone production. These data suggest that the leptin-induced MAPK signal transduction pathway interferes with cAMP/PKA-stimulated steroidogenesis in human granulosa cells. Moreover, siRNA mediated knock-down of the endogenous leptin receptor attenuates the effect of leptin on cAMP-induced StAR protein expression and progesterone

  2. Diazinon-Induced Ovarian Toxicity and Protection by Vitamins E

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    Zinat Sargazi

    2014-09-01

    Full Text Available Background: DZN (diazinon is an organophosphate insecticide that had been used in agriculture and for domestic and veterinary use for several years and caused many negative effects on plants and animal species, especially on human. The aim of present study was to evaluate the effects of DZN on MDA (malondialdehyde and GSH (glutathione levels in female rat reproductive tissue (ovary and to assess the protective role of vitamin E. Methods: A total of 30 adult female Wistar rats were divided into five groups: control group (without any intervention, sham group (received only pure corn oil, as solvent, experimental group 1 (DZN+corn oil, 60 mg/kg, experimental group 2 (vitamin E, 200 mg/kg, and experimental group 3 (DZN+vitamin E, the same dosage. All drugs were injected intraperitoneally, except vitamin E which was administrated by gavage. The animals were scarified after two weeks and MDA as a marker of lipid peroxidation and GSH content were measured in ovarian tissue. Results: DZN reduced GSH content and increased MDA level in ovary compared with the control group (P<0.001. Vitamin E plus DZN increased GSH content but decreased DZN-induced MDA elevation in rat ovarian tissue. Conclusion: Oxidative stress contributes to DZN-induced ovarian toxicity. The results of this study suggested that vitamin E may have a protective effect on DZN-induced ovarian toxicity.

  3. Pediatric ovarian tumors in a tertiary care hospital of Kolkata: An experience of last 5 years with its clinicopathological correlation

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    Senjuti Dasgupta

    2016-01-01

    Full Text Available Background: Pediatric ovarian tumors are rare with an approximate incidence of 2.6 per 100,000 girls per year. Aims and Objectives: This study was done to delineate the clinicopathological profile of pediatric ovarian masses encountered in a tertiary care hospital over 5 years. Materials and Methods: A retrospective study was conducted for a period of 5 years during which all patients whose age did not exceed 20 years and underwent surgical resection of ovarian masses, were included. History, operative notes, gross findings, and microscopic features of each case were noted. Results: A total of 76 cases were included in the study. The age of patients ranged between 2 and 20 years with a mean of 17 ± 2.5 years. Of the 76 cases, 53 (69.7% were benign and 23 (30.3% malignant tumors. The benign tumors included 16 cases each of teratoma (21.1% and serous cystadenoma (21.1%, and 21 cases of mucinous cystadenoma (27.6%. Germ cell tumors were the commonest malignant tumors in patients up to 15 years of age and they included four cases of dysgerminoma (5.3% and one case of immature teratoma (1.3%. Between 16 and 20 years, 8 cases of serous cystadenocarcinoma were found (10.5%, in addition to seven malignant germ cell tumors (9.2%. One case (1.3% each of granulosa cell tumor and sertoli leydig cell tumor was also found in the same age group. Conclusion: Pediatric ovarian tumors require early attention and institution of appropriate treatment since they bear important implications on the future lives of young females.

  4. Anti-Müllerian hormone: plasma levels in women with polycystic ovary syndrome and with premature ovarian failure

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    Piotr Skałba

    2011-06-01

    Full Text Available Background: Anti-Müllerian hormone (AMH is a member of the transforming growth factor β (TGF-β family of growth and differentiation factors. AMH is produced by granulosa cells of preantral and small antral follicles.Aim of the study: The aim of the study was to assess the AMH plasma levels of healthy women in reproductive age and in women with polycystic ovary syndrome (PCOS and premature ovarian failure (POF.Material and methods: The study included 187 women.Results: AMH concentration in serum of patients with PCOS (73.68 ±25.58 pmol/l was significantly higher than in healthy women (16.97 ±5.80 pmol/l (p < 0.05. In patients with POF AMH concentrations in blood serum were very low or undetectable, and averaged 0.65 ±1.81 pmol/l. Average concentrations of AMH in the blood serum of the healthy group of patients differed significantly (p < 0.001 between the age-dependent subgroups. AMH concentration in serum of healthy women decreased with age. The average concentration of AMH in the blood serum in PCOS decreased after 30 years of age. There were no statistically significant differences between age subgroups.In the premature ovarian failure patients with secondary amenorrhea persisting for at least three years AMH plasma levels were extremely low (0.16 ±0.10 pmol/l and showed a significant difference compared to patients whose menses returned.Conclusions:1. In PCOS women the determination of AMH plasma levels can be used to assess severity of the syndrome.2. The determination of AMH in blood serum can be used as a marker of diminished ovarian reserve in premature ovarian failure women.

  5. Pelvic inflammatory disease and risk of invasive ovarian cancer and ovarian borderline tumors

    DEFF Research Database (Denmark)

    Rasmussen, Christina B; Faber, Mette T; Jensen, Allan;

    2013-01-01

    The aim of the study was to examine the potential association between a history of pelvic inflammatory disease (PID) and risk of epithelial ovarian cancer or ovarian borderline tumors.......The aim of the study was to examine the potential association between a history of pelvic inflammatory disease (PID) and risk of epithelial ovarian cancer or ovarian borderline tumors....

  6. Stem cell-like gene expression in ovarian cancer predicts type II subtype and prognosis.

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    Matthew Schwede

    Full Text Available Although ovarian cancer is often initially chemotherapy-sensitive, the vast majority of tumors eventually relapse and patients die of increasingly aggressive disease. Cancer stem cells are believed to have properties that allow them to survive therapy and may drive recurrent tumor growth. Cancer stem cells or cancer-initiating cells are a rare cell population and difficult to isolate experimentally. Genes that are expressed by stem cells may characterize a subset of less differentiated tumors and aid in prognostic classification of ovarian cancer. The purpose of this study was the genomic identification and characterization of a subtype of ovarian cancer that has stem cell-like gene expression. Using human and mouse gene signatures of embryonic, adult, or cancer stem cells, we performed an unsupervised bipartition class discovery on expression profiles from 145 serous ovarian tumors to identify a stem-like and more differentiated subgroup. Subtypes were reproducible and were further characterized in four independent, heterogeneous ovarian cancer datasets. We identified a stem-like subtype characterized by a 51-gene signature, which is significantly enriched in tumors with properties of Type II ovarian cancer; high grade, serous tumors, and poor survival. Conversely, the differentiated tumors share properties with Type I, including lower grade and mixed histological subtypes. The stem cell-like signature was prognostic within high-stage serous ovarian cancer, classifying a small subset of high-stage tumors with better prognosis, in the differentiated subtype. In multivariate models that adjusted for common clinical factors (including grade, stage, age, the subtype classification was still a significant predictor of relapse. The prognostic stem-like gene signature yields new insights into prognostic differences in ovarian cancer, provides a genomic context for defining Type I/II subtypes, and potential gene targets which following further

  7. Survivorship Care Planning in Improving Quality of Life in Survivors of Ovarian Cancer

    Science.gov (United States)

    2016-08-19

    Cancer Survivor; Stage IA Ovarian Epithelial Cancer; Stage IB Ovarian Epithelial Cancer; Stage IC Ovarian Epithelial Cancer; Stage IIA Ovarian Epithelial Cancer; Stage IIB Ovarian Epithelial Cancer; Stage IIC Ovarian Epithelial Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIB Ovarian Epithelial Cancer; Stage IIIC Ovarian Epithelial Cancer

  8. Exercise May Help Thwart Ovarian Cancer

    Science.gov (United States)

    ... page: https://medlineplus.gov/news/fullstory_159486.html Exercise May Help Thwart Ovarian Cancer Chronic inactivity linked ... TUESDAY, June 21, 2016 (HealthDay News) -- Lack of exercise is associated with an increased risk of ovarian ...

  9. The effect of monosaccharide sugars and pyruvate on the differentiation and metabolism of sheep granulosa cells in vitro.

    Science.gov (United States)

    Campbell, B K; Onions, V; Kendall, N R; Guo, L; Scaramuzzi, R J

    2010-10-01

    The objective of this study was to investigate the effect of three monosaccharides or pyruvate on the ability of gonadotrophins to induce cellular proliferation and differentiation of cultured sheep granulosa cells. Lactate production and levels of mRNA expression for the glucose transporters SLC2A1, SLC2A4, SLC2A5 and SLC2A8 were also determined. No energy source in the culture media reduced cell number (50%) and oestradiol (E(2)) production. Dose and type of monosaccharide had a highly significant (Pculture in the presence of fructose and glucose. These data show that glucose, metabolised under anoxic conditions to lactate, is the preferred energy substrate to support the gonadotrophin-induced differentiation of ovine granulosa cells in vitro, and that fructose and pyruvate, but not galactose, are alternative energy substrates despite marked differences in the way these substrates are metabolised. PMID:20634389

  10. The methoxychlor metabolite, HPTE, directly inhibits the catalytic activity of cholesterol side-chain cleavage (P450scc) in cultured rat ovarian cells.

    Science.gov (United States)

    Akgul, Yucel; Derk, Raymond C; Meighan, Terence; Rao, K Murali Krishna; Murono, Eisuke P

    2008-01-01

    Exposure to the pesticide methoxychlor in rodents is linked to impaired steroid production, ovarian atrophy and reduced fertility. Following in vivo administration, it is rapidly converted by the liver to 2,2-bis-(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), the reported active metabolite. Both methoxychlor and HPTE have weak estrogenic and antiandrogenic activities, and these effects are thought to be mediated through the estrogen and androgen receptors, respectively. Previous in vivo studies on methoxychlor exposure to female animals have demonstrated decreased progesterone production but no change in serum estrogen levels. We recently showed that HPTE specifically inhibits the P450 cholesterol side-chain cleavage (P450scc, CYP11A1) step resulting in decreased androgen production by cultured rat testicular Leydig cells. The current studies examined the mechanism of action of HPTE on progesterone production by cultured ovarian cells (granulosa and theca-interstitial) from pregnant mare serum gonadotropin-primed immature rats. In addition, we evaluated whether the effects of HPTE on rat ovarian cell progesterone biosynthesis were mediated through the estrogen or androgen receptors. Exposure to HPTE (0, 10, 50 or 100nM) alone progressively inhibited progesterone formation in cultured theca-interstitial and granulosa cells and the P450scc catalytic activity in theca-interstitial cells in a dose-dependent manner with significant declines starting at 50nM. However, HPTE did not change mRNA levels of the P450scc system (P450scc, adrenodoxin reductase and adrenodoxin) as well as P450scc protein levels. Of interest, estradiol, xenoestrogens (bisphenol-A or 4-tert-octylphenol), a pure antiestrogen (ICI 182,780), or antiandrogens (4-hydroxyflutamide or the vinclozolin metabolite M-2), had no effect on progesterone production even at 1000nM. Co-treatment of HPTE with ICI 182,780 did not block the effect of HPTE on progesterone formation. These studies suggest that the

  11. Human pituitary and placental hormones control human insulin-like growth factor II secretion in human granulosa cells.

    OpenAIRE

    Ramasharma, K; Li, C. H.

    1987-01-01

    Human granulosa cells cultured with calf serum actively proliferated for 18-20 generation and secreted progesterone into the medium; progesterone levels appeared to decline with increase in generation number. Cells cultured under serum-free conditions secreted significant amounts of progesterone and insulin-like growth factor II (IGF-II). The progesterone secretion was enhanced by the addition of human follitropin, lutropin, and chorionic gonadotropin but not by growth hormone. These cells, w...

  12. Transcriptome profiling of sheep granulosa cells and oocytes during early follicular development obtained by Laser Capture Microdissection

    OpenAIRE

    Bonnet Agnes; Bevilacqua Claudia; Benne Francis; Bodin Loys; Cotinot Corinne; Liaubet Laurence; Sancristobal Magali; Sarry Julien; Terenina Elena; Martin Patrice; Tosser-Klopp Gwenola; Mandon-Pepin Beatrice

    2011-01-01

    Abstract Background Successful achievement of early folliculogenesis is crucial for female reproductive function. The process is finely regulated by cell-cell interactions and by the coordinated expression of genes in both the oocyte and in granulosa cells. Despite many studies, little is known about the cell-specific gene expression driving early folliculogenesis. The very small size of these follicles and the mixture of types of follicles within the developing ovary make the experimental st...

  13. Genetic analysis of ovarian microcystic stromal tumor

    OpenAIRE

    Lee, Jae Hoon; Kim, Hyun-Soo; Cho, Nam Hoon; Lee, Jung-Yun; Kim, Sunghoon; Kim, Sang Wun; Kim, Young Tae; Nam, Eun Ji

    2016-01-01

    Microcystic stromal tumor (MCST) of the ovary is a rare subtype of ovarian tumor first described in 2009. Although high nuclear expression of β-catenin and β-catenin gene (CTNNB1) mutation are related with ovarian MCST, the origin and genetic background of ovarian MCST remain unclear. In this study, two cases of ovarian MCST are presented. Microscopically, the tumors showed a microcystic pattern and regions with lobulated cellular masses with intervening hyalinized, fibrous stroma. Tumor cell...

  14. An Update on Ovarian Aging and Ovarian Reserve Tests

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    Migraci Tosun

    2016-12-01

    Full Text Available Ovaries are the female organs that age more quickly than other tissues such as the uterus, the pituitary gland or pancreas. Different from males, an interesting question is why and how the females lose fertility so rapidly. During the aging process, both the number and quality of the oocytes in the ovaries decrease and reach to a point beyond that no more viable offspring may be produced and the associated cyclic endocrinological activities cease, entering the menopause in females at an average age of 50 years. Females who delayed childbearing with or without their willing until their 30 years or 40 years constitute the largest portion of the total infertility population. Ovarian reserve tests (ORTs provide an indirect estimate of a female�s diminishing ovarian reserve or remaining follicular pool. This article briefly reviews recent progresses in relation to ovarian aging and ORTs.

  15. Human pituitary and placental hormones control human insulin-like growth factor II secretion in human granulosa cells

    Energy Technology Data Exchange (ETDEWEB)

    Ramasharma, K.; Li, C.H.

    1987-05-01

    Human granulosa cells cultured with calf serum actively proliferated for 18-20 generations and secreted progesterone into the medium; progesterone levels appeared to decline with increase in generation number. Cells cultured under serum-free conditions secreted significant amounts of progesterone and insulin-like growth factor II (IGF-II). The progesterone secretion was enhanced by the addition of human follitropin, lutropin, and chorionic gonadotropin but not by growth hormone. These cells, when challenged to varying concentrations of human growth hormone, human chorionic somatomammotropin, human prolactin, chorionic gonadotropin, follitropin, and lutropin, secreted IGF-II into the medium as measured by specific IGF-II RIA. Among these human hormones, chorionic gonadotropin, follitropin, and lutropin were most effective in inducing IGF-II secretion from these cells. When synthetic lutropin-releasing hormone and ..cap alpha..-inhibin-92 were tested, only lutropin-releasing hormone was effective in releasing IGF-II. The results described suggest that cultured human granulosa cells can proliferate and actively secrete progesterone and IGF-II into the medium. IGF-II production in human granulosa cells was influenced by a multi-hormonal complex including human growth hormone, human chorionic somatomammotropin, and prolactin.

  16. Human pituitary and placental hormones control human insulin-like growth factor II secretion in human granulosa cells

    International Nuclear Information System (INIS)

    Human granulosa cells cultured with calf serum actively proliferated for 18-20 generations and secreted progesterone into the medium; progesterone levels appeared to decline with increase in generation number. Cells cultured under serum-free conditions secreted significant amounts of progesterone and insulin-like growth factor II (IGF-II). The progesterone secretion was enhanced by the addition of human follitropin, lutropin, and chorionic gonadotropin but not by growth hormone. These cells, when challenged to varying concentrations of human growth hormone, human chorionic somatomammotropin, human prolactin, chorionic gonadotropin, follitropin, and lutropin, secreted IGF-II into the medium as measured by specific IGF-II RIA. Among these human hormones, chorionic gonadotropin, follitropin, and lutropin were most effective in inducing IGF-II secretion from these cells. When synthetic lutropin-releasing hormone and α-inhibin-92 were tested, only lutropin-releasing hormone was effective in releasing IGF-II. The results described suggest that cultured human granulosa cells can proliferate and actively secrete progesterone and IGF-II into the medium. IGF-II production in human granulosa cells was influenced by a multi-hormonal complex including human growth hormone, human chorionic somatomammotropin, and prolactin

  17. A retrospective study of ovarian cysts

    Directory of Open Access Journals (Sweden)

    Shivaji Neelgund

    2016-06-01

    Conclusions: Unilocular simple ovarian cysts are usually functional ovarian cysts and resolve spontaneously. Therapy by 3 to 6 months of Oral Contraceptives, usually resolves them and this also helps to distinguish between physiological and pathological ovarian cysts [Int J Reprod Contracept Obstet Gynecol 2016; 5(6.000: 1969-1973

  18. Do We Know What Causes Ovarian Cancer?

    Science.gov (United States)

    ... Next Topic Can ovarian cancer be prevented? Do we know what causes ovarian cancer? We don’t yet know exactly what causes most ovarian cancers. As discussed in the previous section, we do know some factors that make a woman ...

  19. Ovarian teratoma and endometritis in a mare

    Science.gov (United States)

    2005-01-01

    Abstract An 8-year-old Arabian mare was admitted for a large ovarian anovulatory follicle. A clinical diagnosis of ovarian tumor and endometritis was established. Histological examinations revealed an ovarian teratoma and a grade II endometritis. Three months after unilateral ovariectomy, the mare was confirmed pregnant and eventually gave birth uneventfully. PMID:16363331

  20. Therapeutic efficacy of amniotic membrane stem cells and adipose tissue stem cells in rats with chemically induced ovarian failure

    OpenAIRE

    Fouad, Hanan; Sabry, Dina; Elsetohy, Khaled; Fathy, Naglaa

    2015-01-01

    The present study was conducted to compare between the therapeutic efficacies of human amniotic membrane-derived stem cells (hAM-MSCs) vs. adipose tissue derived stem cells (AD-MSCs) in cyclophosphamide (CTX)-induced ovarian failure in rats. Forty-eight adult female rats were included in the study; 10 rats were used as control group. Thirty-eight rats were injected with CTX to induce ovarian failure and divided into four groups: ovarian failure (IOF) (IOF group), IOF + phosphate buffer saline...

  1. Inactivation of Retinoblastoma Protein (Rb1 in the Oocyte: Evidence That Dysregulated Follicle Growth Drives Ovarian Teratoma Formation in Mice.

    Directory of Open Access Journals (Sweden)

    Qi-En Yang

    2015-07-01

    Full Text Available The origin of most ovarian tumors is undefined. Here, we report development of a novel mouse model in which conditional inactivation of the tumor suppressor gene Rb1 in oocytes leads to the formation of ovarian teratomas (OTs. While parthenogenetically activated ooctyes are a known source of OT in some mutant mouse models, enhanced parthenogenetic propensity in vitro was not observed for Rb1-deficient oocytes. Further analyses revealed that follicle recruitment and growth is disrupted in ovaries of mice with conditional inactivation of Rb1, leading to abnormal accumulation of secondary/preantral follicles. These findings underpin the concept that miscues between the germ cell and somatic compartments cause premature oocyte activation and the formation of OTs. Furthermore, these results suggest that defects in folliculogenesis and a permissive genetic background are sufficient to drive OT development, even in the absence of enhanced parthenogenetic activation. Thus, we have discovered a novel role of Rb1 in regulating the entry of primordial oocytes into the pool of growing follicles and signaling between the oocyte and granulosa cells during the protracted process of oocyte growth. Our findings, coupled with data from studies of other OT models, suggest that defects in the coordinated regulation between growth of the oocyte and somatic components in follicles are an underlying cause of OT formation.

  2. Ricinus communis L. stem bark extracts regulate ovarian cell functions and secretory activity and their response to Luteinising hormone.

    Science.gov (United States)

    Nath, S; Kadasi, A; Grossmann, R; Sirotkin, A V; Kolesarova, A; Talukdar, A D; Choudhury, M D

    2015-01-01

    Ricinus communis L. has ethnopharmacological contraceptive reputation but its stem bark has unexplored mechanisms of action in female reproductive system. In the present study, the effect of methanolic and aqueous extracts from the stem bark of the plant was examined on basic porcine ovarian granulosa cell functions and its response to Luteinising hormone (LH)-the upstream hormonal regulator. Systemic treatment of methanolic and aqueous extracts stimulated cell proliferation (proliferating cell nuclear antigen, PCNA) and also promoted cell apoptosis (caspase-3). Aqueous extract has inverted the stimulatory effect of LH on PCNA but not on caspase-3. Methanolic extract stimulated as well as inhibited progesterone release and stimulated testosterone secretion. Whereas aqueous extract inhibited both steroid releases and suppressed the stimulatory effect of LH on progesterone release and promoted the inhibitory effect of LH on testosterone release. In conclusion, the present study unveils the mechanism of action of R. communis stem bark in in vitro condition. These suggest its possible contraceptive efficacy by exerting its regulatory role over LH and on basic ovarian cell functions and secretion activity.

  3. Molecular imaging in ovarian cancer.

    Science.gov (United States)

    Reyners, A K L; Broekman, K E; Glaudemans, A W J M; Brouwers, A H; Arts, H J G; van der Zee, A G J; de Vries, E G E; Jalving, M

    2016-04-01

    Ovarian cancer has a high mortality and novel-targeted treatment strategies have not resulted in breakthroughs for this disease. Insight into the molecular characteristics of ovarian tumors may improve diagnosis and selection of patients for treatment with targeted therapies. A potential way to achieve this is by means of molecular imaging. Generic tumor processes, such as glucose metabolism ((18)F-fluorodeoxyglucose) and DNA synthesis ((18)F-fluorodeoxythymidine), can be visualized non-invasively. More specific targets, such as hormone receptors, growth factor receptors, growth factors and targets of immunotherapy, can also be visualized. Molecular imaging can capture data on intra-patient tumor heterogeneity and is of potential value for individualized, target-guided treatment selection. Early changes in molecular characteristics during therapy may serve as early predictors of response. In this review, we describe the current knowledge on molecular imaging in the diagnosis and as an upfront or early predictive biomarker in patients with ovarian cancer. PMID:27141066

  4. Testosterone for Poor Ovarian Responders

    DEFF Research Database (Denmark)

    Polyzos, Nikolaos P; Davis, Susan R; Drakopoulos, Panagiotis;

    2016-01-01

    Testosterone, an androgen that directly binds to the androgen receptor, has been shown in previous small randomized controlled trials to increase the reproductive outcomes of poor ovarian responders. In most of these studies, transdermal testosterone in relatively high doses was administered before...... ovarian stimulation with a duration varying from 5 to 21 days. Nevertheless, the key question to be asked is whether, based on ovarian physiology and testosterone pharmacokinetics, a short course of testosterone administration of more than 10 mg could be expected to have any beneficial effect...... on reproductive outcome. The rationale for asking this question lies in the existing scientific evidence derived from basic research and animal studies regarding the action of androgens during folliculogenesis, showing that their main effect in follicular development is defined during the earlier developmental...

  5. M- CSF对人卵巢颗粒细胞表达FSH与其受体的影响及相互作用研究%Effect of macrophage colony-stimulating factor (M-CSF) on expression of follicle stimulating hormone (FSH) and its receptor in human granulosa cells

    Institute of Scientific and Technical Information of China (English)

    许嵩; 张治芬

    2014-01-01

    目的:通过研究巨噬细胞集落刺激因子(M- CSF)对卵巢颗粒细胞表达卵泡刺激素(FSH)与其受体(FSHR)的影响及其与FSH之间的相互作用,探讨M- CSF在卵泡发育中的作用。方法体外培养人卵巢肿瘤颗粒细胞系COV434,分别给予不同浓度的M- CSF(0、5、10、25、50、100ng/ml)进行干预,24h后收取细胞和培养上清液,用荧光定量PCR法检测颗粒细胞内FSH受体表达量的变化,并用同法检测FSH对M- CSF及其受体M- CSFR的作用。用ELISA方法对上清液中细胞分泌的雌二醇(E2)进行检测,观察M- CSF对颗粒细胞分泌E2的影响。结果 M- CSF可使颗粒细胞FSHR的表达上升,呈剂量依赖性,当M- CSF浓度>10ng/ml时,上升更为明显(P<0.01);FSH可以提升M- CSF及其受体在颗粒细胞内的表达,但当FSH浓度过高时(>50ng/ml),此作用消失;M- CSF和FSH在体外条件下达到一定浓度后可以促进E2的分泌。结论 M- CSF能够促进颗粒细胞表达FSH受体和分泌E2,协助FSH发挥促卵泡发育的作用。%Objective To examine the effect of macrophage colony- stimulating factor (M- CSF) on the expression of fol i-cle stimulating hormone (FSH) and its receptor (FSHR) in human non- luteinizing granulosa cells. Methods The cultured human ovarian granulosa celltumor COV434 cells were treated with different concentrations of M- CSF (0, 5, 10, 25, 50, 100ng/ml). After 24 h, granulosa cells were col ected and the mRNA expression of FSHR, M- CSF and M- CSF receptor was detected by quantita-tive PCR. Estradiol (E2) contents in culture supernatant were measured by ELISA. Results M- CSF significantly increased the mRNA expression of FSHR in a dose dependent manner (P10ng/ml. FSH enhanced the production of M- CSF and its receptor when the concentration<50ng/ml. Both M- CSF and FSH increased the secretion of E2 in granulosa cells. Conclusion M- CSF can increase the expression of FSHR and E2

  6. Ovarian Cancer Pathogenesis: A Model in Evolution

    Directory of Open Access Journals (Sweden)

    Alison M. Karst

    2010-01-01

    Full Text Available Ovarian cancer is a deadly disease for which there is no effective means of early detection. Ovarian carcinomas comprise a diverse group of neoplasms, exhibiting a wide range of morphological characteristics, clinical manifestations, genetic alterations, and tumor behaviors. This high degree of heterogeneity presents a major clinical challenge in both diagnosing and treating ovarian cancer. Furthermore, the early events leading to ovarian carcinoma development are poorly understood, thus complicating efforts to develop screening modalities for this disease. Here, we provide an overview of the current models of ovarian cancer pathogenesis, highlighting recent findings implicating the fallopian tube fimbria as a possible site of origin of ovarian carcinomas. The ovarian cancer model will continue to evolve as we learn more about the genetics and etiology of this disease.

  7. Expression of 17beta- and 3beta-hydroxysteroid dehydrogenases and steroidogenic acute regulatory protein in non-luteinizing bovine granulosa cells in vitro.

    Science.gov (United States)

    Sahmi, M; Nicola, E S; Silva, J M; Price, C A

    2004-08-31

    Granulosa cells of small follicles differentiate in vitro in serum-free medium, resulting in increased estradiol secretion and abundance of mRNA encoding cytochrome P450aromatase (P450arom). We tested the hypothesis that differentiation in vitro also involves increased expression of 3beta- and 17beta-hydroxysteroid dehydrogenases (HSD) in the absence of steroidogenic acute regulatory protein (StAR) expression, as has been observed in vivo. Granulosa cells from small (basal layer of the membrana granulosa) did not affect steroidogenesis. We conclude that under the present cell culture system granulosa cells do not luteinize, and show expression of key steroidogenic enzymes in patterns similar to those occurring in differentiating follicles in vivo. Further, the data suggest that 17beta-HSD may be as important as P450arom in regulating estradiol secretion, and that 3beta-HSD is more important than P450scc as a regulator of progesterone secretion in non-luteinizing granulosa cells. PMID:15279910

  8. Palliative Care in Improving Quality of Life and Symptoms in Patients With Stage III-IV Pancreatic or Ovarian Cancer

    Science.gov (United States)

    2014-12-18

    Recurrent Ovarian Epithelial Cancer; Recurrent Ovarian Germ Cell Tumor; Recurrent Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IIIA Ovarian Epithelial Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIB Ovarian Epithelial Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIC Ovarian Epithelial Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Pancreatic Cancer

  9. Natural mixtures of persistent organic pollutants (POPs) suppress ovarian follicle development, liver vitellogenin immunostaining and hepatocyte proliferation in female zebrafish (Danio rerio)

    International Nuclear Information System (INIS)

    Persistent organic pollutants such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and dichlorodiphenyltrichloroethane (DDT) are present in high concentrations in livers of burbot (Lota lota) in Lake Mjøsa, Norway. In order to assess effects of such pollutants on fish gonadal morphology, female zebrafish were exposed in two generations by food to mixtures of pollutants extracted from livers of burbot from Lake Mjøsa (high and low dose) and Lake Losna, which represents background pollution, and compared to a control group. Ovarian follicle counts detected a significant decrease in late vitellogenic follicle stages in fish exposed to the Losna and the high concentrations of Mjøsa mixtures in fish from the first generation. In addition, proliferation of granulosa cells, visualized by immunohistochemistry against proliferating cell nuclear antigen (PCNA), was decreased in all exposure groups in either early or late vitellogenic follicle stages compared to control. This was accompanied by increased apoptosis of granulosa cells. There was a decrease in proliferation of liver hepatocytes with exposure to both Mjøsa mixtures. In addition, immunopositivity for vitellogenin in the liver was significantly lower in the Mjøsa high group than in the control group. When analysing effects of parental exposure, fish with parents exposed to Mjøsa high mixture had significantly higher numbers of perinucleolar follicles than fish with control parents. We conclude that long-term exposure of a real-life mixture of pollutants containing high- and background levels of chemicals supress ovarian follicle development, liver vitellogenin immunostaining intensity and hepatocyte proliferation in the zebrafish model.

  10. STMN1 Promotes Progesterone Production Via StAR Up-regulation in Mouse Granulosa Cells

    Science.gov (United States)

    Dou, Yun-De; Zhao, Han; Huang, Tao; Zhao, Shi-Gang; Liu, Xiao-Man; Yu, Xiao-Chen; Ma, Zeng-Xiang; Zhang, Yu-Chao; Liu, Tao; Gao, Xuan; Li, Lei; Lu, Gang; Chan, Wai-Yee; Gao, Fei; Liu, Hong-Bin; Chen, Zi-Jiang

    2016-01-01

    Stathmin 1 (STMN1) is a biomarker in several types of neoplasms. It plays an important role in cell cycle progression, mitosis, signal transduction and cell migration. In ovaries, STMN1 is predominantly expressed in granulosa cells (GCs). However, little is known about the role of STMN1 in ovary. In this study, we demonstrated that STMN1 is overexpressed in GCs in patients with polycystic ovary syndrome (PCOS). In mouse primary GCs, the overexpression of STMN1 stimulated progesterone production, whereas knockdown of STMN1 decreased progesterone production. We also found that STMN1 positively regulates the expression of Star (steroidogenic acute regulatory protein) and Cyp11a1 (cytochrome P450 family 11 subfamily A member 1). Promoter and ChIP assays indicated that STMN1 increased the transcriptional activity of Star and Cyp11a1 by binding to their promoter regions. The data suggest that STMN1 mediates the progesterone production by modulating the promoter activity of Star and Cyp11a1. Together, our findings provide novel insights into the molecular mechanisms of STMN1 in ovary GC steroidogenesis. A better understanding of this potential interaction between STMN1 and Star in progesterone biosynthesis in GCs will facilitate the discovery of new therapeutic targets in PCOS. PMID:27270953

  11. Establishment and validation of a model for non-luteinized human mural granulosa cell culture.

    Science.gov (United States)

    Ophir, L; Yung, Y; Maman, E; Rubinstein, N; Yerushalmi, G M; Haas, J; Barzilay, E; Hourvitz, A

    2014-03-25

    Cell culture techniques of human mural granulosa cells (MGCs) serve as a major in vitro tool. However, the use of luteinized MGCs has major limitations due to their luteinized state. Our aim was to establish a standardized protocol for the culture of MGCs as a model for different stages of folliculogenesis. We showed that early-non-luteinized, preovulatory-non-luteinized and luteal-MGCs have distinct gene expression pattern. After 4 days of incubation of luteinized-MGCs, ovulatory genes mRNA's achieve expression levels similar to the early non-luteinized follicles. FSH stimulation for 48 h of these 4 days cultured MGCs showed ovulatory genes mRNA's expression similar to the pre-ovulatory non-luteinized follicles. These FSH-stimulated cells responded to hCG stimulation in a pattern similar to the response of pre-ovulatory follicles. This novel model may provide a standardized research tool for delineation of the molecular processes occurring during the latter stages of follicular development in the human ovary.

  12. Hereditary breast and ovarian cancer

    DEFF Research Database (Denmark)

    Nielsen, Finn Cilius; van Overeem Hansen, Thomas; Sørensen, Claus Storgaard

    2016-01-01

    Genetic abnormalities in the DNA repair genes BRCA1 and BRCA2 predispose to hereditary breast and ovarian cancer (HBOC). However, only approximately 25% of cases of HBOC can be ascribed to BRCA1 and BRCA2 mutations. Recently, exome sequencing has uncovered substantial locus heterogeneity among...

  13. Genomic profile of ovarian carcinomas

    OpenAIRE

    Micci, Francesca; Haugom, Lisbeth; Vera M. Abeler; Davidson, Ben; Tropé, Claes G; Heim, Sverre

    2014-01-01

    Background It is known that all tumors studied in sufficient number to draw conclusions show characteristic/specific chromosomal rearrangements, and the identification of these chromosomes and the genes rearranged behind the aberrations may ultimately lead to a tailor-made therapy for each cancer patient. Knowledge about the acquired genomic aberrations of ovarian carcinomas is still unsatisfactory. Methods ...

  14. Ovarian Cancer Risk Prediction Models

    Science.gov (United States)

    Developing statistical models that estimate the probability of developing ovarian cancer over a defined period of time will help clinicians identify individuals at higher risk of specific cancers, allowing for earlier or more frequent screening and counseling of behavioral changes to decrease risk.

  15. Ovarian cancer and body size

    DEFF Research Database (Denmark)

    Mosgaard, Berit Jul

    2012-01-01

    Only about half the studies that have collected information on the relevance of women's height and body mass index to their risk of developing ovarian cancer have published their results, and findings are inconsistent. Here, we bring together the worldwide evidence, published and unpublished, and...

  16. Ovarian stimulation and embryo quality

    NARCIS (Netherlands)

    Baart, Esther; Macklon, Nick S.; Fauser, Bart J. C. M.

    2009-01-01

    To Study the effects of different ovarian stimulation approaches on oocyte and embryo quality, it is imperative to assess embryo quality with a reliable and objective method. Embryos rated as high quality by standardized morphological assessment are associated with higher implantation and pregnancy

  17. Ultrasound in evaluating ovarian reserve

    Directory of Open Access Journals (Sweden)

    Eman Ahmaed Shawky Sabek

    2015-12-01

    Full Text Available The objective of this study was to compare the diagnostic accuracy of transvaginal ultrasound (TVS, as a less invasive technique instead of hormonal assay to evaluate the ovarian reserve. This study included fifty-five females with breast cancer and we compared the ovarian reserve for these patients by hormonal assay through measuring the serum AntiMullerian Hormone (AMH level and follicular stimulating hormone (FSH level before and after chemotherapy, and by transvaginal ultrasound through the ovarian volume (OV calculation and counting the Antral follicles (AFC before and after chemotherapy treatment. There was decline in the AntiMullerian Hormone level after chemotherapy by 27 ± 11.19% and decrease in the Antral follicle counts by 21 ± 13.43%. In conclusion there was strong relation between AMH level and AFC which makes the use of transvaginal ultrasound is a reliable alternative method to the hormonal assay to detect the ovarian reserve.

  18. Early Detection of Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Donna Badgwell

    2007-01-01

    Full Text Available Despite advances in therapy, ovarian cancer remains the most deadly of the gynecological cancers. Less than 30% of women with advanced stage disease survive long-term. When diagnosed in stage I, up to 90% of patients can be cured with conventional surgery and chemotherapy. At present, only 25% of ovarian cancers are detected in stage I due, in part, to the absence of specific symptoms and to lack of an effective screening strategy. Early detection of ovarian cancer might significantly improve the overall survival rate of women with ovarian cancer if 1 most cancers are clonal and unifocal, arising in the ovary rather than in the peritoneum, 2 metastatic disease results from progression of clinically detectable stage I lesions, and 3 cancers remain localized for a sufficient interval to permit cost-effective screening. Given the prevalence of ovarian cancer, strategies for early detection must have high sensitivity for early stage disease (> 75%, but must have extremely high specificity (99.6% to attain a positive predictive value of at least 10%. Transvaginal sonography (TVS, serum markers and a combination of the two modalities have been evaluated for early detection of ovarian cancer. Among the serum markers, CA125 has received the most attention, but lacks the sensitivity or specificity to function alone as a screening test. Greater specificity can be achieved by combining CA125 and TVS and/or by monitoring CA125 over time. Two stage screening strategies promise to be cost effective, where abnormal serum assays prompt TVS to detect lesions that require laparotomy. Accrual has been completed for a 200,000 woman trial in the United Kingdom that will test the ability of a rising CA125 to trigger TVS and subsequent exploratory surgery. Given the heterogeneity of ovarian cancer, it is unlikely that any single marker will be sufficiently sensitive to provide an effective initial screen. Sensitivity of serum assays might be enhanced by utilizing a

  19. Endometrial and ovarian carcinomas with undifferentiated components: clinically aggressive and frequently underrecognized neoplasms.

    Science.gov (United States)

    Tafe, Laura J; Garg, Karuna; Chew, Ivy; Tornos, Carmen; Soslow, Robert A

    2010-06-01

    Carcinomas of the endometrium and ovary with undifferentiated components are uncommon neoplasms that are likely underdiagnosed. They are important to recognize as they have been shown to be clinically aggressive. We identified 32 carcinomas with undifferentiated components as defined by Silva and co-workers, 26 endometrial and 6 of ovarian origin. The patient age ranged from 21 to 76 years (median 55); 40% of patients were focal nuclear pleomorphism and eight cases had variably sized zones of rhabdoid cells in a background of myxoid stroma. The tumors were frequently misdiagnosed; they received a wide range of diagnoses, including FIGO grade 2 or 3 endometrioid carcinoma, carcinosarcoma, high-grade sarcoma including endometrial stromal sarcoma, neuroendocrine carcinoma, lymphoma, granulosa cell tumor and epithelioid sarcoma. Up to 86% of the cases showed focal, but strong keratin and/or epithelial membrane antigen staining, with CK18 being the most frequently positive keratin stain. They were predominantly negative for neuroendocrine markers, smooth muscle markers and estrogen receptor/progesterone receptor. Mismatch repair protein expression by immunohistochemistry was evaluated in 17 cases, and 8 (47%) were abnormal (7 with loss of MLH1/PMS2 and 1 with MSH6 loss). Follow-up was available for 27 patients, although it was very short in many cases, ranging from 0.5 to 89 months (median 9 months). Eleven patients (41%) died of the disease in 0.5-20 months, four are alive with disease and twelve patients have no evidence of disease. Endometrial and ovarian carcinomas with undifferentiated components have a broad histologic differential diagnosis, but they show specific histologic features that should enable accurate diagnosis. These tumors can occur in young women, may be associated with microsatellite instability and behave in a clinically aggressive manner.

  20. Potential protective effect of arginine against 4-nitrophenol-induced ovarian damage in rats.

    Science.gov (United States)

    Xu, Wei-Feng; Li, Yan-Sen; Dai, Peng-Yuan; Li, Chun-Mei

    2016-01-01

    4-nitrophenol (PNP) is generally regarded as a diesel exhaust particle (DEP). Arginine plays an important role as a new feed additive, possessing highly efficient antioxidant activities. Here we investigated the effects of dietary supplementation with arginine against ovarian damage induced by PNP in rats. A total of thirty-two female rats postnatal day 28 (PND 28) were randomly divided into four groups. Two groups were fed with basal diet or 13 g/kg arginine in diet for 4 weeks, respectively; the other two groups were given PNP (100 mg/kg b.w.) daily by subcutaneous injection for 2 weeks following pretreatment with either basal diet or arginine diet for 2 weeks. The values of body weight gain (BWG), average daily gain (ADG) and percentage weight gain (PWG) upon PNP treatment were significantly reduced than those in other groups. The relative liver weight in the PNP group was significantly decreased compared with the control group. Treatment with PNP significant reduced the number of corpora lutea, although serum 17β-estradiol (E2) and progesterone (P4) concentrations were unchanged. The morphology of the ovaries in PNP-treated rats displayed necrosis, follicular deformation and granulosa cells irregular arrangement. Moreover, exposure to PNP enhanced production of malondialdehyde (MDA) and hydrogen peroxide (H2O2), and decreased the activities of total superoxide dismutase (T-SOD) and catalase (CAT), and the co-administration of arginine can attenuate the oxidative stress caused by PNP. These results suggest that arginine may have a protective effect against ovarian damage induced by PNP owing to its antioxidant capacity effect. PMID:27193729

  1. Ovarian cysts on prenatal MRI

    International Nuclear Information System (INIS)

    Objective: Ovarian cysts are the most frequently encountered intra-abdominal masses in females in utero. They may, at times, require perinatal intervention. Using magnetic resonance imaging (MRI) as an adjunct to ultrasonography (US) in prenatal diagnosis, we sought to demonstrate the ability to visualize ovarian cysts on prenatal MRI. Materials and methods: This retrospective study included 17 fetal MRI scans from 16 female fetuses (23–37 gestational weeks) with an MRI diagnosis of ovarian cysts after suspicious US findings. A multiplanar MRI protocol was applied to image and to characterize the cysts. The US and MRI findings were compared, and the prenatal findings were compared with postnatal imaging findings or histopathology. Results: Simple ovarian cysts were found in 10/16 cases and complex cysts in 7/16 cases, including one case with both. In 11/16 (69%) cases, US and MRI diagnoses were in agreement, and, in 5/16 (31%) cases, MRI specified or expanded the US diagnosis. In 6/16 cases, postnatal US showed that the cysts spontaneously resolved or decreased in size, and in 1/16 cases, postnatal imaging confirmed a hemorrhagic cyst. In 4/16 cases, the prenatal diagnoses were confirmed by surgery/histopathology, and for the rest, postnatal correlation was not available. Conclusion: Our results illustrate the MRI visualization of ovarian cysts in utero. In most cases, MRI will confirm the US diagnosis. In certain cases, MRI may provide further diagnostic information, additional to US, which is the standard technique for diagnosis, monitoring, and treatment planning.

  2. Ovarian cysts on prenatal MRI

    Energy Technology Data Exchange (ETDEWEB)

    Nemec, Ursula [Department of Radiology, Division of Neuroradiology and Musculoskeletal Radiology, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Nemec, Stefan F., E-mail: stefan.nemec@meduniwien.ac.at [Department of Radiology, Division of Neuroradiology and Musculoskeletal Radiology, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Medical Genetics Institute, Cedars Sinai Medical Center, 8700 Beverly Boulevard, PACT Suite 400, Los Angeles, CA 90048 (United States); Bettelheim, Dieter [Department of Obstetrics and Gynaecology, Division of Prenatal Diagnosis and Therapy, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Brugger, Peter C. [Center of Anatomy and Cell Biology, Integrative Morphology Group, Medical University Vienna, Waehringerstrasse 13, A-1090 Vienna (Austria); Horcher, Ernst [Department of Pediatric Surgery, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Schoepf, Veronika [Department of Radiology, Division of Neuroradiology and Musculoskeletal Radiology, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria); Graham, John M.; Rimoin, David L. [Medical Genetics Institute, Cedars Sinai Medical Center, 8700 Beverly Boulevard, PACT Suite 400, Los Angeles, CA 90048 (United States); Weber, Michael; Prayer, Daniela [Department of Radiology, Division of Neuroradiology and Musculoskeletal Radiology, Medical University Vienna, Waehringer Guertel 18-20, A-1090 Vienna (Austria)

    2012-08-15

    Objective: Ovarian cysts are the most frequently encountered intra-abdominal masses in females in utero. They may, at times, require perinatal intervention. Using magnetic resonance imaging (MRI) as an adjunct to ultrasonography (US) in prenatal diagnosis, we sought to demonstrate the ability to visualize ovarian cysts on prenatal MRI. Materials and methods: This retrospective study included 17 fetal MRI scans from 16 female fetuses (23-37 gestational weeks) with an MRI diagnosis of ovarian cysts after suspicious US findings. A multiplanar MRI protocol was applied to image and to characterize the cysts. The US and MRI findings were compared, and the prenatal findings were compared with postnatal imaging findings or histopathology. Results: Simple ovarian cysts were found in 10/16 cases and complex cysts in 7/16 cases, including one case with both. In 11/16 (69%) cases, US and MRI diagnoses were in agreement, and, in 5/16 (31%) cases, MRI specified or expanded the US diagnosis. In 6/16 cases, postnatal US showed that the cysts spontaneously resolved or decreased in size, and in 1/16 cases, postnatal imaging confirmed a hemorrhagic cyst. In 4/16 cases, the prenatal diagnoses were confirmed by surgery/histopathology, and for the rest, postnatal correlation was not available. Conclusion: Our results illustrate the MRI visualization of ovarian cysts in utero. In most cases, MRI will confirm the US diagnosis. In certain cases, MRI may provide further diagnostic information, additional to US, which is the standard technique for diagnosis, monitoring, and treatment planning.

  3. Role of TGF-β1 in the Formation of Ovarian Interstitial Fibrosis in PCOS Rat

    Institute of Scientific and Technical Information of China (English)

    Zhu-lin MIAO; Zu-neng WANG; Yan-dong YANG; Long-qiu CHEN; Rong CUI; Xiao-lan WANG; Ru-qiang OU

    2008-01-01

    Objective To study the role of TGF-β1 in the formation of interstitial fibrosis and capsular thickening in the PCOS rats.Methods PCOS rat model were established by subcutaneous injection DHEA.Estradiol(E2).testosterone(T).follicular stimulating hormone(FSH).Iuteinizing hormone(LH).LH/FSH and fasting insulin(FINS)hormone values of the model were tested by microparticle enzyme immunoassay,the pathohistology of PCOS rat ovaries was observed by HE staining,and their ultrastructure was tested by transmission electron microscope(TEM).The expressions of TGF-β1 in PCOS group(n=20),and control group(n=20)were detected and evaluated by immunohistochemistry and image analysis system.Results The results of serum E2,T,LH/FSH,FINS,the ovarian pathological-histology and the ultrastructure showed that the model was esmblished successfully.Compared with control group:there was no significant difference of TGF-β1,expression intensity in oocytes,granulosa cells of the different developing stages of follicle in PCOS(P>0.05).But it was markedly higher expressed in the theca cells of antral follicles(P<0.01).and stromal cells(P<0.05)in PCOS group than in control group.Conclusion The abnormal expression of TGF-β1 in PCOS is the main cause of capsular thickening and interstitial fibrosis.TGF-β1 also takes part in regulating PCOS follicle development and atresia.

  4. Lactational exposure to hexavalent chromium delays puberty by impairing ovarian development, steroidogenesis and pituitary hormone synthesis in developing Wistar rats

    International Nuclear Information System (INIS)

    Hexavalent chromium (Cr-VI) is used in a wide range of industries. Cr-VI from chromate industries and atmospheric emissions contribute to the Cr contamination in the environment. Cr is a reproductive metal toxicant that can traverse the placental barrier and cause a wide range of fetal effects including ovotoxicity. Therefore, the goal of this study was to investigate the basic mechanisms involved in Cr(VI)-induced ovotoxicity, and the protective role of vitamin C on ovarian follicular development and function in Cr(VI)-induced reproductive toxicity using both in vivo and in vitro approaches. Lactating rats received potassium dichromate (200 mg/L) with or without vitamin C (500 mg/L), through drinking water from postpartum days 1-21. During postnatal days (PND) 1-21 the pups received Cr(VI) via the mother's milk. Pups from both control and treatment groups were continued on regular diet and water from PND-21 onwards, and euthanized on PND-21, -45 and -65. Cr(VI) decreased steroidogenesis, GH and PRL, increased FSH and did not alter LH. Cr(VI) delayed puberty, decreased follicle number, and extended estrous cycle. Spontaneously immortalized rat granulosa cells were treated with 12.5 μM (IC50) potassium dichromate for 12 and 24 h, with or without vitamin C pre-treatment. Cr(VI) decreased the mRNA expressions of StAR, SF-1, 17β-HSD-1, 17β-HSD-2, FSHR, LHR, ERα and ERβ. Vitamin C pre-treatment protected ovary and granulosa cells from the deleterious effects of Cr(VI) toxicity, both in vivo and in vitro. Therefore, Cr(VI) toxicity could be a potential risk to the reproductive system in developing females, and vitamin C plays a protective role against Cr(VI)-induced ovotoxicity

  5. Photoperiod-gonadotropin mismatches induced by treatment with acyline or FSH in Siberian hamsters: impacts on ovarian structure and function.

    Science.gov (United States)

    Zysling, D A; Park, S-U; McMillan, E L; Place, N J

    2012-11-01

    Many seasonal breeders time their reproductive efforts to specific times of the year to ensure adequate resources for the production and care of young. For long-day (LD) breeders, females born before the summer solstice (LDs) reach sexual maturity quickly and often breed that same year, whereas females born after the summer solstice (short days (SDs)) may delay reproductive development to the following spring when environmental conditions are favorable for reproduction. In Siberian hamsters, development in SD is associated with structural and functional differences in the ovary compared with females held in LD, including a greater number of primordial follicles and an abundance of hypertrophied granulosa cells (HGCs), which are immunoreactive for anti-Müllerian hormone. The goal of this study was to determine whether SD-induced gonadotropin suppression is responsible for these phenotypic differences. Gonadotropin levels were suppressed in LD hamsters using the GNRH antagonist acyline. Conversely, to determine whether the SD ovarian phenotype is completely reversed by gonadotropin stimulation, recombinant human FSH (rhFSH) was administered. Our treatments were successful in mimicking FSH concentrations of the opposite photoperiod, but they did not produce a comparable change in the ovarian phenotype. Most notable was the lack of HGCs in the ovaries of acyline-treated LD females. Similarly, HGCs were maintained in the ovaries of SD females treated with rhFSH. Our data suggest that gonadotropins alone do not account for the SD ovarian phenotype. Future studies will determine whether SD-induced changes in other factors underlie these phenotypic changes.

  6. Identification of the key regulating genes of diminished ovarian reserve (DOR) by network and gene ontology analysis.

    Science.gov (United States)

    Pashaiasl, Maryam; Ebrahimi, Mansour; Ebrahimie, Esmaeil

    2016-09-01

    Diminished ovarian reserve (DOR) is one of the reasons for infertility that not only affects both older and young women. Ovarian reserve assessment can be used as a new prognostic tool for infertility treatment decision making. Here, up- and down-regulated gene expression profiles of granulosa cells were analysed to generate a putative interaction map of the involved genes. In addition, gene ontology (GO) analysis was used to get insight intol the biological processes and molecular functions of involved proteins in DOR. Eleven up-regulated genes and nine down-regulated genes were identified and assessed by constructing interaction networks based on their biological processes. PTGS2, CTGF, LHCGR, CITED, SOCS2, STAR and FSTL3 were the key nodes in the up-regulated networks, while the IGF2, AMH, GREM, and FOXC1 proteins were key in the down-regulated networks. MIRN101-1, MIRN153-1 and MIRN194-1 inhibited the expression of SOCS2, while CSH1 and BMP2 positively regulated IGF1 and IGF2. Ossification, ovarian follicle development, vasculogenesis, sequence-specific DNA binding transcription factor activity, and golgi apparatus are the major differential groups between up-regulated and down-regulated genes in DOR. Meta-analysis of publicly available transcriptomic data highlighted the high coexpression of CTGF, connective tissue growth factor, with the other key regulators of DOR. CTGF is involved in organ senescence and focal adhesion pathway according to GO analysis. These findings provide a comprehensive system biology based insight into the aetiology of DOR through network and gene ontology analyses. PMID:27324248

  7. Morphological classification of bovine ovarian follicles.

    Science.gov (United States)

    Rodgers, R J; Irving-Rodgers, H F

    2010-02-01

    Follicle classification is an important aid to the understanding of follicular development and atresia. Some bovine primordial follicles have the classical primordial shape, but ellipsoidal shaped follicles with some cuboidal granulosa cells at the poles are far more common. Preantral follicles have one of two basal lamina phenotypes, either a single aligned layer or one with additional layers. In antral follicles basal granulosa cells and additional layers of basal lamina, which appear as loops in cross section ('loopy'). The remainder have aligned single-layered follicular basal laminas with rounded basal cells, and contain better quality oocytes than the loopy/columnar follicles. In sizes >5 mm, only aligned/rounded phenotypes are present. Dominant and subordinate follicles can be identified by ultrasound and/or histological examination of pairs of ovaries. Atretic follicles basal atretic or antral atretic, named on the basis of the location in the membrana granulosa where cells die first. Basal atretic follicles have considerable biological differences to antral atretic follicles. In follicles >5 mm, only antral atresia is observed. The concentrations of follicular fluid steroid hormones can be used to classify atresia and distinguish some of the different types of atresia; however, this method is unlikely to identify follicles early in atresia, and hence misclassify them as healthy. Other biochemical and histological methods can be used, but since cell death is a part of normal homoeostatis, deciding when a follicle has entered atresia remains somewhat subjective. PMID:19786400

  8. Clinicopathologic features of ovarian neoplasms with emphasis on borderline ovarian tumors: an institutional perspective

    OpenAIRE

    Hashmi, Atif Ali; Hussain, Zubaida Fida; Bhagwani, Aneel Roy; Edhi, Muhammad Muzzammil; Faridi, Naveen; Hussain, Syed Danish; Khan, Mehmood

    2016-01-01

    Background Ovarian cancer is the most lethal gynecologic malignancy and it represents third most common malignancy in Karachi (after breast and oral cancer). Due to lack of well established cancer registry in our country, changing trends of ovarian tumors has not been determined. Therefore we aimed to establish the current trends and classification of ovarian tumors in our setup according to latest WHO guidelines. Methods We retrospectively analyzed 162 cases of ovarian tumors that underwent ...

  9. Extracellular Signal-regulated Kinase (ERK)-dependent Phosphorylation of Y-Box-binding Protein 1 (YB-1) Enhances Gene Expression in Granulosa Cells in Response to Follicle-stimulating Hormone (FSH).

    Science.gov (United States)

    Donaubauer, Elyse M; Hunzicker-Dunn, Mary E

    2016-06-01

    Within the ovarian follicle, immature oocytes are surrounded and supported by granulosa cells (GCs). Stimulation of GCs by FSH leads to their proliferation and differentiation, events that are necessary for fertility. FSH activates multiple signaling pathways to regulate genes necessary for follicular maturation. Herein, we investigated the role of Y-box-binding protein-1 (YB-1) within GCs. YB-1 is a nucleic acid binding protein that regulates transcription and translation. Our results show that FSH promotes an increase in the phosphorylation of YB-1 on Ser(102) within 15 min that is maintained at significantly increased levels until ∼8 h post treatment. FSH-stimulated phosphorylation of YB-1(Ser(102)) is prevented by pretreatment of GCs with the PKA-selective inhibitor PKA inhibitor (PKI), the MEK inhibitor PD98059, or the ribosomal S6 kinase-2 (RSK-2) inhibitor BI-D1870. Thus, phosphorylation of YB-1 on Ser(102) is PKA-, ERK-, and RSK-2-dependent. However, pretreatment of GCs with the protein phosphatase 1 (PP1) inhibitor tautomycin increased phosphorylation of YB-1(Ser(102)) in the absence of FSH; FSH did not further increase YB-1(Ser(102)) phosphorylation. This result suggests that the major effect of RSK-2 is to inhibit PP1 rather than to directly phosphorylate YB-1 on Ser(102) YB-1 coimmunoprecipitated with PP1β catalytic subunit and RSK-2. Transduction of GCs with the dephospho-adenoviral-YB-1(S102A) mutant prevented the induction by FSH of Egfr, Cyp19a1, Inha, Lhcgr, Cyp11a1, Hsd17b1, and Pappa mRNAs and estradiol-17β production. Collectively, our results reveal that phosphorylation of YB-1 on Ser(102) via the ERK/RSK-2 signaling pathway is necessary for FSH-mediated expression of target genes required for maturation of follicles to a preovulatory phenotype. PMID:27080258

  10. Early Detection Biomarkers for Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Sreeja Sarojini

    2012-01-01

    Full Text Available Despite the widespread use of conventional and contemporary methods to detect ovarian cancer development, ovarian cancer remains a common and commonly fatal gynecological malignancy. The identification and validation of early detection biomarkers highly specific to ovarian cancer, which would permit development of minimally invasive screening methods for detecting early onset of the disease, are urgently needed. Current practices for early detection of ovarian cancer include transvaginal ultrasonography, biomarker analysis, or a combination of both. In this paper we review recent research on novel and robust biomarkers for early detection of ovarian cancer and provide specific details on their contributions to tumorigenesis. Promising biomarkers for early detection of ovarian cancer include KLK6/7, GSTT1, PRSS8, FOLR1, ALDH1, and miRNAs.

  11. Ovarian cancer immunotherapy: opportunities, progresses and challenges

    Directory of Open Access Journals (Sweden)

    Stevens Richard

    2010-02-01

    Full Text Available Abstract Due to the low survival rates from invasive ovarian cancer, new effective treatment modalities are urgently needed. Compelling evidence indicates that the immune response against ovarian cancer may play an important role in controlling this disease. We herein summarize multiple immune-based strategies that have been proposed and tested for potential therapeutic benefit against advanced stage ovarian cancer. We will examine the evidence for the premise that an effective therapeutic vaccine against ovarian cancer is useful not only for inducing remission of the disease but also for preventing disease relapse. We will also highlight the questions and challenges in the development of ovarian cancer vaccines, and critically discuss the limitations of some of the existing immunotherapeutic strategies. Finally, we will summarize our own experience on the use of patient-specific tumor-derived heat shock protein-peptide complex for the treatment of advanced ovarian cancer.

  12. Statin use and risk for ovarian cancer

    DEFF Research Database (Denmark)

    Baandrup, L; Dehlendorff, C; Friis, Søren;

    2015-01-01

    BACKGROUND: Limited data suggest that statin use reduces the risk for ovarian cancer. METHODS: Using Danish nationwide registries, we identified 4103 cases of epithelial ovarian cancer during 2000-2011 and age-matched them to 58,706 risk-set sampled controls. Conditional logistic regression was...... used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for epithelial ovarian cancer overall, and for histological types, associated with statin use. RESULTS: We observed a neutral association between ever use of statins and epithelial ovarian cancer risk (OR=0.98, 95% CI=0.......87-1.10), and no apparent risk variation according to duration, intensity or type of statin use. Decreased ORs associated with statin use were seen for mucinous ovarian cancer (ever statin use: OR=0.63, 95% CI=0.39-1.00). CONCLUSIONS: Statin use was not associated with overall risk for epithelial ovarian cancer...

  13. Transcriptome profiling of sheep granulosa cells and oocytes during early follicular development obtained by Laser Capture Microdissection

    Directory of Open Access Journals (Sweden)

    Bonnet Agnes

    2011-08-01

    Full Text Available Abstract Background Successful achievement of early folliculogenesis is crucial for female reproductive function. The process is finely regulated by cell-cell interactions and by the coordinated expression of genes in both the oocyte and in granulosa cells. Despite many studies, little is known about the cell-specific gene expression driving early folliculogenesis. The very small size of these follicles and the mixture of types of follicles within the developing ovary make the experimental study of isolated follicular components very difficult. The recently developed laser capture microdissection (LCM technique coupled with microarray experiments is a promising way to address the molecular profile of pure cell populations. However, one main challenge was to preserve the RNA quality during the isolation of single cells or groups of cells and also to obtain sufficient amounts of RNA. Using a new LCM method, we describe here the separate expression profiles of oocytes and follicular cells during the first stages of sheep folliculogenesis. Results We developed a new tissue fixation protocol ensuring efficient single cell capture and RNA integrity during the microdissection procedure. Enrichment in specific cell types was controlled by qRT-PCR analysis of known genes: six oocyte-specific genes (SOHLH2, MAEL, MATER, VASA, GDF9, BMP15 and three granulosa cell-specific genes (KL, GATA4, AMH. A global gene expression profile for each follicular compartment during early developmental stages was identified here for the first time, using a bovine Affymetrix chip. Most notably, the granulosa cell dataset is unique to date. The comparison of oocyte vs. follicular cell transcriptomes revealed 1050 transcripts specific to the granulosa cell and 759 specific to the oocyte. Functional analyses allowed the characterization of the three main cellular events involved in early folliculogenesis and confirmed the relevance and potential of LCM-derived RNA. Conclusions

  14. New Report of Two Species of Crabs, Cycloes granulosa and Pugettia vulgaris (Crustacea: Decapoda Collected from Korea

    Directory of Open Access Journals (Sweden)

    Yang, Kea Cheong

    2015-07-01

    Full Text Available Two species of crabs, Cycloes granulosa and Pugettia vulgaris, are described and illustrated for the first time in Korea. The former is the first species of calappoid genus Cycloes and characterized by having a minute lateral spine on the margin of carapace. The latter is a species of majoid crab and similar to P. pellucens. However, it can be distinguished by shorter rostral spines, a smaller hepatic spine, and a carapace entirely covered with short setae. In Korea the calappoid crab now includes seven species of three genera (Calappa, Mursia, and Cycloes and the majoid genus Pugettia consists of six species.

  15. Decidualized Ovarian Endometrioma in a Pregnant Woman Mimicking Ovarian Malignancy: Magnetic Resonance Imaging and Ultrasonographic Findings

    Directory of Open Access Journals (Sweden)

    Izza Rozalli

    2015-10-01

    Full Text Available Decidualized ovarian endometrioma is a rare phenomenon in pregnancy, which can mimic ovarian malignancy in imaging and often poses a diagnostic challenge. We report a case of a large ruptured decidualized ovarian endometrioma in a 15 weeks gestation patient, and we will describe the imaging characteristics (ultrasonography and MR imaging findings and the histopathological findings (macro- and microscopically.

  16. Decidualized Ovarian Endometrioma in a Pregnant Woman Mimicking Ovarian Malignancy: Magnetic Resonance Imaging and Ultrasonographic Findings.

    Science.gov (United States)

    Izza Rozalli, Faizatul; Rahmat, Kartini; Fadzli, Farhana; Boylan, Colm; Deb, Pratima

    2015-10-01

    Decidualized ovarian endometrioma is a rare phenomenon in pregnancy, which can mimic ovarian malignancy in imaging and often poses a diagnostic challenge. We report a case of a large ruptured decidualized ovarian endometrioma in a 15 weeks gestation patient, and we will describe the imaging characteristics (ultrasonography and MR imaging findings) and the histopathological findings (macro- and microscopically). PMID:26715980

  17. Decidualized Ovarian Endometrioma in a Pregnant Woman Mimicking Ovarian Malignancy: Magnetic Resonance Imaging and Ultrasonographic Findings

    OpenAIRE

    Izza Rozalli; Rahmat; Fadzli; Boylan; Deb

    2015-01-01

    Decidualized ovarian endometrioma is a rare phenomenon in pregnancy, which can mimic ovarian malignancy in imaging and often poses a diagnostic challenge. We report a case of a large ruptured decidualized ovarian endometrioma in a 15 weeks gestation patient, and we will describe the imaging characteristics (ultrasonography and MR imaging findings) and the histopathological findings (macro- and microscopically).

  18. Incipient ovarian failure and premature ovarian failure show the same immunological profile

    NARCIS (Netherlands)

    van Kasteren, YM; von Blomberg, M; Hoek, A; de Koning, C; Lambalk, N; van Montfrans, J; Kuik, J

    2000-01-01

    PROBLEM: Incipient ovarian failure (IOF) is characterized by regular menstrual cycles, infertility and a raised early-follicular FSH in women under 40. IOF might be a precursor or a mitigated form of premature ovarian failure (POF). Disturbances in the immune system may play a role in ovarian failur

  19. Novel population of small tumour-initiating stem cells in the ovaries of women with borderline ovarian cancer

    Science.gov (United States)

    Virant-Klun, Irma; Stimpfel, Martin

    2016-01-01

    Small stem cells with diameters of up to 5 μm previously isolated from adult human ovaries indicated pluripotency and germinal lineage, especially primordial germ cells, and developed into primitive oocyte-like cells in vitro. Here, we show that a comparable population of small stem cells can be found in the ovarian tissue of women with borderline ovarian cancer, which, in contrast to small stem cells in “healthy” ovaries, formed spontaneous tumour-like structures and expressed some markers related to pluripotency and germinal lineage. The gene expression profile of these small putative cancer stem cells differed from similar cells sorted from “healthy” ovaries by 132 upregulated and 97 downregulated genes, including some important forkhead box and homeobox genes related to transcription regulation, developmental processes, embryogenesis, and ovarian cancer. These putative cancer stem cells are suggested to be a novel population of ovarian tumour-initiating cells in humans. PMID:27703207

  20. Immature ovarian teratoma in a postmenopausal woman

    DEFF Research Database (Denmark)

    Ornvold, K; Detlefsen, G U; Horn, T;

    1987-01-01

    We report the first case of immature ovarian teratoma occurring after menopause in a 57-year-old, 3 years postmenopausal woman. Within one year after resection of the teratoma she developed peritoneal botryoid rhabdomyosarcoma, which probably originated from initially unrecognized rhabdomyoblasts...... in the teratoma. The patient died 6 months later from progressive disease after a transient adriamycin-induced tumor response. The literature on ovarian immature teratoma and ovarian rhabdomyosarcoma is briefly reviewed, and the available treatment is discussed....

  1. Prohibitin regulates the FSH signaling pathway in rat granulosa cell differentiation.

    Science.gov (United States)

    Chowdhury, Indrajit; Thomas, Kelwyn; Zeleznik, Anthony; Thompson, Winston E

    2016-05-01

    Published results from our laboratory identified prohibitin (PHB), a gene product expressed in granulosa cells (GCs) that progressively increases during follicle maturation. Our current in vitro studies demonstrate that follicle-stimulating hormone (FSH) stimulates Phb expression in rat primary GCs. The FSH-dependent expression of PHB was primarily localized within mitochondria, and positively correlates with the morphological changes in GCs organelles, and synthesis and secretions of estradiol (E2) and progesterone (P4). In order to confirm that PHB plays a regulatory role in rat GC differentiation, endogenous PHB-knockdown studies were carried out in undifferentiated GCs using adenoviral (Ad)-mediated RNA interference methodology. Knockdown of PHB in GCs resulted in the suppression of the key steroidogenic enzymes including steroidogenic acute regulatory protein (StAR), p450 cholesterol side-chain cleavage enzyme (p450scc), 3β-hydroxysteroid dehydrogenase (3β-HSD), and aromatase (Cyp19a1); and decreased E2 and P4 synthesis and secretions in the presence of FSH stimulation. Furthermore, these experimental studies also provided direct evidence that PHB within the mitochondrial fraction in GCs is phosphorylated at residues Y249, T258, and Y259 in response to FSH stimulation. The observed levels of phosphorylation of PHB at Y249, T258, and Y259 were significantly low in GCs in the absence of FSH stimulation. In addition, during GC differentiation FSH-induced expression of phospho-PHB (pPHB) requires the activation of MEK1-ERK1/2 signaling pathway. Taken together, these studies provide new evidence supporting FSH-dependent PHB/pPHB upregulation in GCs is required to sustain the differentiated state of GCs.

  2. Primary ovarian pregnancy with intrauterine contraceptive device

    Directory of Open Access Journals (Sweden)

    Sabita Saichandran

    2015-08-01

    Full Text Available Primary ovarian pregnancy is a rare variant of extra-uterine pregnancies. However the cause for primary ovarian pregnancy is still obscure. Some studies have reported a strong correlation of this condition with intrauterine contraceptive device (IUCD. The diagnosis of ovarian ectopic pregnancy is seldom made before surgery though ultrasound proves to be an invaluable tool for its diagnosis. We describe here about a case of primary ovarian pregnancy which was diagnosed only at the time of operation and was managed with wedge resection of the ovary. [Int J Reprod Contracept Obstet Gynecol 2015; 4(4.000: 1191-1193

  3. Cytoplasmic localization of Lrh-1 down-regulates ovarian follicular cyp19a1a expression in a teleost, the orange-spotted grouper Epinephelus coioides.

    Science.gov (United States)

    Lu, Huijie; Zhang, Shen; Liu, Qiongyou; Zhang, Lihong; Zhang, Weimin

    2014-08-01

    Liver receptor homolog-1 (LRH-1) is a conserved member of the NR5A subfamily in vertebrates and a potential regulator of estrogen synthesis in the ovarian granulosa cells. An Lrh-1 homologue was obtained from the orange-spotted grouper Epinephelus coioides that contains the conserved structural features of NR5A and is phylogenetically closely related to NR5A2. The expression of the orange-spotted grouper Lrh-1 is tissue-specific with relatively higher levels in the liver and ovary. The immunoreactive signals for Lrh-1 and Cyp19a1a were present in the ovarian follicular cells and germ cells. In the ovarian follicular cells, Lrh-1 was present both in the nucleus and cytoplasm, and colocalized with Cyp19a1a. The expression levels of both increased during vitellogenesis whereas only Cyp19a1a dramatically decreased toward maturation when Lrh-1 was localized almost exclusively to the cytoplasm of the follicular cells. The orange-spotted grouper Lrh-1 could up-regulate cyp19a1a transcription in vitro via the two conserved Ftz-f1 sites in cyp19a1a promoter. Chromatin immunoprecipitation analysis showed that the orange-spotted grouper Lrh-1 could bind cyp19a1a promoter in vivo with a higher abundance in the vitellogenic ovary, whereas the binding was dramatically decreased in the mature ovary. Taken together, the results of present study demonstrate that Lrh-1 plays an important role in up-regulating cyp19a1a gene in the ovarian follicular cells during vitellogenesis, and the sequestration of Lrh-1 to the cytoplasm may down-regulate cyp19a1a expression in the mature ovary. This mechanism for modifying transcriptional roles of the orange-spotted grouper Lrh-1 may shed new light on the regulation of Cyp19a1 expression in other vertebrates as well.

  4. Ultrasonographic findings of ovarian teratomas

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Il Gi; Kwak, Dong Yeob; Kim, Si Woon; Lee, Jong Gil [Fatima Hospital, Taegu (Korea, Republic of)

    1986-04-15

    24 cases of surgically proven ovarian teratomas were analyzed. 1. The most prevalent age group was 3rd decades (57%). 2. The size of most tumors falls into 5-15cm (96%). 3. The site of involvement was more common on left side than right. 4. Well developed teeth or bones were identified in 9 patients on simple abdominal films (39%). 5. Ultrasonographic findings of the tumors were purely cystic in 3 cases (12.5%), mixed in 15 cases (62.5%), and solid in 6 cases (25%). 6. Among mixed typed masses, predominant cystic tumors were 11 cases, and the remained (4 cases) were predominantly solid type. 7. Various ultrasonic findings were seen such as hair-fluid level, linear echoes, scattered echoes, nodular intermixed dense echoes, papillary echogenic mass, and calcifications. 8. Echogenic nodular foci on nonindependent portion were considered to be a helpful diagnostic sign of ovarian teratomas.

  5. [Cytostatic treatment of ovarian carcinoma].

    Science.gov (United States)

    Neijt, J P

    1999-10-30

    Shortly after treatment with the cytostatic combination of cisplatin and paclitaxel was generally accepted as the standard therapy for patients with epithelial ovarian carcinoma, many have come to regard the combination of carboplatin and paclitaxel as a better choice. The latter combination causes fewer side effects and may be used in the outpatient clinic. Conceivably, the carboplatin-paclitaxel scheme will shortly have to be adjusted again owing to results of current research. The intensive basic research of recent years, namely, is beginning to yield benefits for the therapeutic arsenal against ovarian carcinoma. Possibilities are inhibitors of the breakdown of extracellular matrix (such as marimastat) and inhibitors of signal transduction (such as trastuzumab). PMID:10578409

  6. Intended care seeking for ovarian cancer symptoms among U.S. women.

    Science.gov (United States)

    Cooper, Crystale Purvis; Gelb, Cynthia A; Trivers, Katrina F; Stewart, Sherri L

    2016-06-01

    To investigate U.S. women's intended care seeking for symptoms associated with ovarian cancer, data from the 2012 HealthStyles Fall survey of U.S. adults were examined. Analyses were limited to women with no history of gynecologic cancer (N = 1726). Logistic regression models for intended care seeking within 2 weeks of symptom onset were developed. A minority of women recognized that unexplained pelvic or abdominal pain (29.9%), unexplained bloating (18.1%), and feeling full after eating a small amount of food (10.1%) can indicate ovarian cancer, and 31.1% mistakenly believed that the Papanicolaou (Pap) test screens for the disease. In the multivariate regression models, the most consistent, significant predictors (p educational efforts should emphasize that symptoms associated with ovarian cancer may also result from benign conditions. PMID:27419020

  7. OVARIAN CALCIFICATION MIMICKING VESICLE CALCULUS

    OpenAIRE

    Pallavi; Pratibha; Santosh Kumar; Neeeta; Kamal

    2013-01-01

    INTRODUCTION: Calcification in ovary is usually dystrophic in natu re, forming secondary to degeneration of the epithelium or in association wit h areas of necrosis. It may occur in cases of endometriosis [1] or in some ovarian tumor eg. Fibro thecoma [2] , Brenner’s tumor [3] , cavernous hemangioma [4] etc. Benign unilateral densely calcified ovary wit hout any association with tumor or endometriosis has not been reported previously. We repo...

  8. Structural changes occurring during atresia in sheep ovarian follicles.

    Science.gov (United States)

    Hay, M R; Cran, D G; Moor, R M

    1976-07-01

    The structural changes that characterize primary, secondary and tertiary atresia in sheep Graafian follicles have been studied by means of histological, histochemical and ultrastructural techniques. In primary atresia vacuoles representing swollen endoplasmic reticulum are prominent along the antral border together with disorganized granulosa cells containing pyknotic nuclei. Phagocytic cells, which increase in number as atresia progresses, were seen within the membrana granulosa and are considered to be transformed granulosa cells. Even in follicles classified as nonatretic, a few antral vacuoles and occasional pyknotic nuclei are present. During secondary atresia there is a large increase in the number of cells with pyknotic nuclei; many of these nuclei had been extruded and had fused to form the characteristic Feulgen-positive atretic bodies found along the edge of the antral cavity. These bodies usually have a diameter of up to 15 mum but occasionally reached as much as 400 mum. A second area of degeneration is frequently present in the membrana granulosa, two or three cell layers from the basal lamina, and it is at this level that exfoliation of granulosa cells occurs in tertiary atresia. In contrast to the membrana granulosa, there are during secondary atresia, only slight indications of degeneration in the cumulus. In tertiary atresia the membrana granulosa is highly disorganized; the atretic bodies are often fewer in number than at earlier stages. The basal lamina remains essentially intact. It is at this stage that the first clear signs of degeneration occur in the theca interna. Despite some disintegration of the cumulus, the integrity of the oocyte is maintained and its nucleus remains vesicular. Changes in the thecal microcirculation may plan a key role in atresia: adjacent to the basal lamina of non-atretic follicles, there is a well-developed capillary network which is significantly reduced as atresia progresses. PMID:991198

  9. Validating genetic risk associations for ovarian cancer through the international Ovarian Cancer Association Consortium

    DEFF Research Database (Denmark)

    Pearce, C L; Near, A M; Van Den Berg, D J;

    2009-01-01

    The search for genetic variants associated with ovarian cancer risk has focused on pathways including sex steroid hormones, DNA repair, and cell cycle control. The Ovarian Cancer Association Consortium (OCAC) identified 10 single-nucleotide polymorphisms (SNPs) in genes in these pathways, which had...... been genotyped by Consortium members and a pooled analysis of these data was conducted. Three of the 10 SNPs showed evidence of an association with ovarian cancer at P... and risk of ovarian cancer suggests that this pathway may be involved in ovarian carcinogenesis. Additional follow-up is warranted....

  10. Anti-Mullerian Hormone: Above and Beyond Conventional Ovarian Reserve Markers

    Science.gov (United States)

    Jamil, Zehra; Fatima, Syeda Sadia; Ahmed, Khalid; Malik, Rabia

    2016-01-01

    Management of ovarian dysfunctions requires accurate estimation of ovarian reserve (OR). Therefore, reproductive hormones and antral follicle count (AFC) are assessed to indicate OR. Serum anti-Mullerian hormone (AMH) is a unique biomarker that has a critical role in folliculogenesis as well as steroidogenesis within ovaries. Secretion from preantral and early antral follicles renders AMH as the earliest marker to show OR decline. In this review we discuss the dynamics of circulating AMH that remarkably vary with sex and age. As it emerges as a marker of gonadal development and reproductive disorders, here we summarize the role of AMH in female reproductive physiology and provide evidence of higher accuracy in predicting ovarian response to stimulation. Further, we attempt to compile potential clinical applications in children and adults. We propose that AMH evaluation has a potential role in effectively monitoring chemotherapy and pelvic radiation induced ovarian toxicity. Furthermore, AMH guided ovarian stimulation can lead to individualization of therapeutic strategies for infertility treatment. However future research on AMH levels within follicular fluid may pave the way to establish it as a marker of “quality” besides “quantity” of the growing follicles. PMID:26977116

  11. Anti-Mullerian Hormone: Above and Beyond Conventional Ovarian Reserve Markers

    Directory of Open Access Journals (Sweden)

    Zehra Jamil

    2016-01-01

    Full Text Available Management of ovarian dysfunctions requires accurate estimation of ovarian reserve (OR. Therefore, reproductive hormones and antral follicle count (AFC are assessed to indicate OR. Serum anti-Mullerian hormone (AMH is a unique biomarker that has a critical role in folliculogenesis as well as steroidogenesis within ovaries. Secretion from preantral and early antral follicles renders AMH as the earliest marker to show OR decline. In this review we discuss the dynamics of circulating AMH that remarkably vary with sex and age. As it emerges as a marker of gonadal development and reproductive disorders, here we summarize the role of AMH in female reproductive physiology and provide evidence of higher accuracy in predicting ovarian response to stimulation. Further, we attempt to compile potential clinical applications in children and adults. We propose that AMH evaluation has a potential role in effectively monitoring chemotherapy and pelvic radiation induced ovarian toxicity. Furthermore, AMH guided ovarian stimulation can lead to individualization of therapeutic strategies for infertility treatment. However future research on AMH levels within follicular fluid may pave the way to establish it as a marker of “quality” besides “quantity” of the growing follicles.

  12. The role for runt related transcription factor 2 (RUNX2) as a transcriptional repressor in luteinizing granulosa cells.

    Science.gov (United States)

    Park, Eun-Sil; Park, Jiyeon; Franceschi, Renny T; Jo, Misung

    2012-10-15

    Transcription factors induced by the LH surge play a vital role in reprogramming the gene expression in periovulatory follicles. The present study investigated the role of RUNX2 transcription factor in regulating the expression of Runx1, Ptgs2, and Tnfaip6 using cultured granulosa cells isolated from PMSG-primed immature rats. hCG or forskolin+PMA induced the transient increase in Runx1, Ptgs2, and Tnfaip6 expression, while the expression of Runx2 continued to increase until 48 h. The knockdown of the agonist-stimulated Runx2 expression increased Runx1, Ptgs2, and Tnfaip6 expression and PGE(2) levels in luteinizing granulosa cells. Conversely, the over-expression of RUNX2 inhibited the expression of these genes and PGE(2) levels. The mutation of RUNX binding motifs in the Runx1 promoter enhanced transcriptional activity of the Runx1 promoter. The knockdown and overexpression of Runx2 increased and decreased Runx1 promoter activity, respectively. ChIP assays revealed the binding of RUNX2 in the Runx1 and Ptgs2 promoters. Together, these novel findings provide support for the role of RUNX2 in down-regulation of Runx1, Ptgs2, and Tnfaip6 during the late ovulatory period to support proper ovulation and/or luteinization.

  13. Amphiregulin mediates hCG-induced StAR expression and progesterone production in human granulosa cells

    Science.gov (United States)

    Fang, Lanlan; Yu, Yiping; Zhang, Ruizhe; He, Jingyan; Sun, Ying-Pu

    2016-01-01

    Progesterone plays critical roles in maintaining a successful pregnancy at the early embryonic stage. Human chorionic gonadotropin (hCG) rapidly induces amphiregulin (AREG) expression. However, it remains unknown whether AREG mediates hCG-induced progesterone production. Thus, the objective of this study was to investigate the role of AREG in hCG-induced progesterone production and the underlying molecular mechanism in human granulosa cells; primary cells were used as the experimental model. We demonstrated that the inhibition of EGFR and the knockdown of AREG abolished hCG-induced steroidogenic acute regulatory protein (StAR) expression and progesterone production. Importantly, follicular fluid AREG levels were positively correlated with progesterone levels in the follicular fluid and serum. Treatment with AREG increased StAR expression and progesterone production, and these stimulatory effects were abolished by EGFR inhibition. Moreover, activation of ERK1/2, but not PI3K/Akt, signaling was required for the AREG-induced up-regulation of StAR expression and progesterone production. Our results demonstrate that AREG mediates hCG-induced StAR expression and progesterone production in human granulosa cells, providing novel evidence for the role of AREG in the regulation of steroidogenesis. PMID:27113901

  14. Toxicological effects of fumonisin B1 alone and in combination with other fusariotoxins on bovine granulosa cells.

    Science.gov (United States)

    Albonico, Marco; Schütz, Luis F; Caloni, Francesca; Cortinovis, Cristina; Spicer, Leon J

    2016-08-01

    There is now overwhelming evidence of global contamination of commodities with Fusarium mycotoxins. Fumonisin B1 (FB1) is a Fusarium mycotoxin frequently occurring in corn in combination with deoxynivalenol (DON), α-zearalenol (α-ZEA) and β-zearalenol (β-ZEA). The aim of this study was to determine if FB1, alone and combined with DON or α-ZEA or β-ZEA, can affect cell proliferation and steroid production of bovine granulosa cells (GC). A species-specific model with bovine granulosa cells (GC) was used to study the potential endocrine disruptor effects of FB1 alone and in co-exposure. In the presence of β-ZEA (30 ng/mL), FB1 at 30 ng/mL showed a stimulatory effect on GC numbers. Insulin-like growth factor-1 (IGF1)-stimulated cell proliferation was decreased after exposure to β-ZEA alone at 5.0 μg/mL and FB1 with α-ZEA and β-ZEA at the same concentration. Regarding steroid production, FB1 at 30 ng/mL and 100 ng/mL amplified the inhibitory effect of β-ZEA (30 ng/mL) on estradiol (E2) production, while FB1 alone increased (P mycotoxin FB1 along with other mycotoxins can affect GC proliferation and steroid production, which ultimately could influence reproductive function in cattle. PMID:27108238

  15. Transfection of isolated rainbow trout, Oncorhynchus mykiss, granulosa cells through chemical transfection and electroporation at 12°C.

    Science.gov (United States)

    Marivin, E; Mourot, B; Loyer, P; Rime, H; Bobe, J; Fostier, A

    2015-09-15

    Over-expression or inhibition of gene expression can be efficiently used to analyse the functions and/or regulation of target genes. Modulation of gene expression can be achieved through transfection of exogenous nucleic acids into target cells. Such techniques require the development of specific protocols to transfect cell cultures with nucleic acids. The aim of this study was to develop a method of transfection suitable for rainbow trout granulosa cells in primary culture. After the isolation of rainbow trout granulosa cells, chemical transfection of cells with a fluorescent morpholino oligonucleotide (MO) was tested using FuGENE HD at 12 °C. Electroporation was also employed to transfect these cells with either a plasmid or MO. Transfection was more efficient using electroporation (with the following settings: 1200 V/40 ms/1p) than chemical transfection, but electroporation by itself was deleterious, resulting in a decrease of the steroidogenic capacity of the cells, measured via estradiol production from its androgenic substrate. The disturbance of cell biology induced by the transfection method per se should be taken into account in data interpretation when investigating the effects of under- or over-expression of candidate genes.

  16. Primary granulosa cell tumor of liver associated with cavernous hemangioma: a case of report and review of literature%肝脏原发粒层细胞瘤伴海绵状血管瘤1例报道并文献复习

    Institute of Scientific and Technical Information of China (English)

    徐晓艳; 王华; 梅放; 钟延丰; 王盛兰; 郑杰

    2012-01-01

    目的 探讨肝脏原发粒层细胞瘤(granulosa cell tumor)伴海绵状血管瘤的临床病理学特点.方法 对1例肝脏原发粒层细胞瘤伴海绵状血管瘤进行组织学观察和免疫组化染色,观察其超微结构及临床影像学特点,并复习相关文献.结果 患者女性,CT及MRI提示肝脏右叶可见一巨大实性肿物,低密度.肉眼见肿物突向肝脏下方,切面呈实性;另外,在肝脏膈面被膜下见一灰红色出血区,呈疏松海绵状.镜下巨大肿物中肿瘤细胞椭圆形或梭形,呈微滤泡状、小梁状排列,部分区域呈实性弥漫状分布,类似于卵巢粒层细胞;部分区域呈束状排列,间质中可见较多胶原纤维瘢痕形成,似孤立性纤维性肿瘤.肿瘤细胞核内可见小核仁,并可见纵形核沟.免疫组化结果示肿瘤细胞CD99、α-inhibin、CK8、CK18、SMA和BCL-2均(+),Ki-67增殖指数<1%.超微结构显示肿瘤细胞可见各种形式的核皱叠形成,部分细胞呈Call-Exner小体样结构排列,偶见桥粒结构,提示该肿瘤与卵巢粒层细胞瘤极其相似.结论 粒层细胞瘤原发于肝脏且合并海绵状血管瘤,非常罕见,目前其临床生物学行为难以确定,需对患者进行长期随访.%Purpose To study the clinicapathological features of primary granulosa cell tumor of liver associated with cavernous hemangioma. Methods One case of primary granulosa cell tumor of liver associated with cavernous hemangioma was studied by histology, immunohistochemistry, ultrastructural analyses and clinical imaging. Results A female patient complained of a mass by CT and MRI. The tumor protruded into the lower portion of the liver, and the cut surface was solid. Diaphragmatic surface of liver shows an area of gray red bleeding and loose sponge-like. The tumor cells were oval or spindle-shaped arranged in micro-follicular or trabecular, some areas showed solid and diffuse distribution, which was similar to ovarian granulosa cells; some areas

  17. Overexpression of Oct4 in porcine ovarian stem/stromal cells enhances differentiation of oocyte-like cells in vitro and ovarian follicular formation in vivo

    OpenAIRE

    Lee, Yeon-Mi; Kim, Tae-ho; Lee, Jeong-Hyeon; Lee, Won-Jae; Jeon, Ryoung-Hoon; Jang, Si-Jung; Ock, Sun-A; Lee, Sung-Lim; Park, Bong-Wook; RHO, Gyu-Jin

    2016-01-01

    Background Recent findings have revealed that the female gonad may have regenerative activity with having germ line stem cells in juveniles and adults. Application of these germ line stem cells could be an alternative therapy for reproductive disorders in regenerative medicine. Methods To enhance the potency of differentiation into oocyte-like cells (OLCs) and folliculogenesis, we overexpressed Oct4 in ovarian stem/stromal cell (OvSCs) and examined the cellular properties related to stemness ...

  18. Effect of fixative type and fixation time on the morphology of equine preantral ovarian follicles

    Directory of Open Access Journals (Sweden)

    Isabela Búfalo

    2016-02-01

    Full Text Available The aim of this study was to investigate the efficacy of the tissue fixatives Bouin, Carnoy and 10% Formaldehyde in equine ovarian fragments. Ovaries (n=4 from mares of mixed breeds were obtained at a local slaughterhouse and transported at 20 ºC in a thermo container. Immediately after collection, the ovaries were washed with a modified PBS solution (Cultilab®, Campinas-SP, Brazil and divided into nine fragments with approximately 5x5x1 mm, removed from the parenchyma of each ovary. The ovarian fragments were then immersed in three different fixatives, Bouin (B Carnoy (C or 10% Formaldehyde (F for 6, 12 or 24 hours. Each fragment was individually immersed in a 20 mL tube containing 20 times the volume of fixative solution. After this period, the fragments were held in 70% ethanol for 24 hours. Each procedure was performed in four replicates. For histological analysis, the specimens were dehydrated in increasing concentrations of alcohol, submitted to diaphanization in xylol and embedded in paraffin. Serial sections of 5 ?m were made with the use of a rotating microtome (Leica® type, Wetzlar, Germany, followed by slide mounting and staining with periodic acid-Schiff (PAS and hematoxylin. A total of 540 slides with 1,620 sections were evaluated, which contained 465 preantral follicles that were classified as normal or degenerated. Follicles were considered as degenerated when presented at least one of the following aspects: cytoplasm retraction, pyknotic nucleus, cytoplasmic vacuoles, displacement of granulosa cells and/or disruption of the basal membrane. A logistic regression test was used for statistical analysis, and differences were considered significant when P<0.05. The Carnoy fixative, when used for 24 hours, provided the best conditions of morphological integrity (53.3%; 32/60 compared to all others, and the use of Boiun for 24 hours was considered the worst treatment (19.1%; 9/47. The other treatments lead to the following results: C

  19. Vasoactive intestinal polypeptide and peptide histidine methionine. Presence in human follicular fluid and effects on DNA synthesis and steroid secretion in cultured human granulosa/lutein cells

    DEFF Research Database (Denmark)

    Gräs, S; Ovesen, P; Andersen, A N;

    1994-01-01

    Vasoactive intestinal polypeptide (VIP) and peptide histidine methionine (PHM) originate from the same precursor molecule, prepro VIP. In the present study we examined the concentrations of VIP and PHM in human follicular fluid and their effects on cultured human granulosa/lutein cells. Follicular...

  20. Granulosa cells from bovine follicles activate different signal transduction pathways dependent on follicle health status and ability to convert androstenedione to estrogen

    Science.gov (United States)

    Since steroidogenesis is a critical component in the development of competent preovulatory follicles we hypothesized that granulosa cells from follicles of cows treated with normal levels of progesterone (CIDR) or with melengestrol acetate (MGA), which results in the development of persistent follic...

  1. MV-NIS or Investigator's Choice Chemotherapy in Treating Patients With Ovarian, Fallopian, or Peritoneal Cancer

    Science.gov (United States)

    2016-06-24

    Fallopian Tube Transitional Cell Carcinoma; Malignant Ovarian Clear Cell Tumor; Malignant Ovarian Endometrioid Tumor; Malignant Ovarian Serous Tumor; Ovarian Seromucinous Carcinoma; Ovarian Transitional Cell Carcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  2. Cigarette smoking and risk of ovarian cancer

    DEFF Research Database (Denmark)

    Faber, Mette T; Kjær, Susanne K; Dehlendorff, Christian;

    2013-01-01

    The majority of previous studies have observed an increased risk of mucinous ovarian tumors associated with cigarette smoking, but the association with other histological types is unclear. In a large pooled analysis, we examined the risk of epithelial ovarian cancer associated with multiple...... measures of cigarette smoking with a focus on characterizing risks according to tumor behavior and histology....

  3. Premature ovarian failure : from phenotype to genotype

    NARCIS (Netherlands)

    Knauff, A.H.

    2009-01-01

    Postponement of childbearing has led to increased rates of age-related female subfertility. Age-related decreases in ovarian follicle numbers and decay in oocyte quality influence the natural loss of fecundity and ultimately the start of menopause. The rate of ovarian ageing is highly variable among

  4. Hormone therapy and different ovarian cancers

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms;

    2012-01-01

    Postmenopausal hormone therapy use increases the risk of ovarian cancer. In the present study, the authors examined the risks of different histologic types of ovarian cancer associated with hormone therapy. Using Danish national registers, the authors identified 909,946 women who were followed fr...

  5. Ovarian cancer mortality and industrial pollution

    International Nuclear Information System (INIS)

    We investigated whether there might be excess ovarian cancer mortality among women residing near Spanish industries, according to different categories of industrial groups and toxic substances. An ecologic study was designed to examine ovarian cancer mortality at a municipal level (period 1997–2006). Population exposure to pollution was estimated by means of distance from town to facility. Using Poisson regression models, we assessed the relative risk of dying from ovarian cancer in zones around installations, and analyzed the effect of industrial groups and pollutant substances. Excess ovarian cancer mortality was detected in the vicinity of all sectors combined, and, principally, near refineries, fertilizers plants, glass production, paper production, food/beverage sector, waste treatment plants, pharmaceutical industry and ceramic. Insofar as substances were concerned, statistically significant associations were observed for installations releasing metals and polycyclic aromatic chemicals. These results support that residing near industries could be a risk factor for ovarian cancer mortality. - Highlights: • We studied excess mortality due to ovarian cancer near Spanish industries. • Integrated nested Laplace approximations were used as a Bayesian inference tool. • We found excess ovarian cancer mortality near all industrial groups as a whole. • Risk also was found in towns near industries releasing carcinogens and metals. • Risk was associated with plants releasing polycyclic aromatic chemicals and POPs. - Our results support that residing in the vicinity of pollutant industries could be a risk factor for ovarian cancer mortality

  6. Hormone therapy and ovarian borderline tumors

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms;

    2012-01-01

    Little is known about the influence of postmenopausal hormone therapy on the risk of ovarian borderline tumors. We aimed at assessing the influence of different hormone therapies on this risk.......Little is known about the influence of postmenopausal hormone therapy on the risk of ovarian borderline tumors. We aimed at assessing the influence of different hormone therapies on this risk....

  7. [Ovarian torsion revealing an ovarian cavernous hemangioma in a child].

    Science.gov (United States)

    M'pemba Loufoua-Lemay, A-B; Peko, J-F; Mbongo, J-A; Mokoko, J-C; Nzingoula, S

    2003-11-01

    The authors report one case of cavernous hemangioma of the left ovary, which was revealed by ovarian torsion. Such benign tumors of the blood vessels are rare in ovaries during childhood. This hemangioma was observed in a 13-year-old patient, who presented with abdominal and pelvic pain and vomiting. The pelvic mass was noted and sonography revealed a cystic tumor. An annexectomia was realized. Histology showed narcotized ovary cells, with an increased number of vascular channels composed of thin walled vessels, whose wall consisted of an endothelium. This aspect evoked a cavernous hemangioma of the ovary. PMID:14613693

  8. Targeted Therapies in Epithelial Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Jurjees Hasan

    2010-02-01

    Full Text Available Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the advantage of long-term therapy with a manageable toxicity profile enabling patients to enjoy a good quality of life. In this review we appraise the emerging data on novel targeted therapies in ovarian cancer. We discuss the role of these compounds in the front-line treatment of ovarian cancer and in relapsed disease; and describe how the development of predictive clinical, molecular and imaging biomarkers will define the role of biological agents in the treatment of ovarian cancer.

  9. Targeted Therapies in Epithelial Ovarian Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dean, Emma; El-Helw, Loaie; Hasan, Jurjees, E-mail: jurjees.hasan@christie.nhs.uk [Christie Hospital NHS Foundation Trust / Wilmslow Road, Manchester, M20 4BX (United Kingdom)

    2010-02-23

    Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the advantage of long-term therapy with a manageable toxicity profile enabling patients to enjoy a good quality of life. In this review we appraise the emerging data on novel targeted therapies in ovarian cancer. We discuss the role of these compounds in the front-line treatment of ovarian cancer and in relapsed disease; and describe how the development of predictive clinical, molecular and imaging biomarkers will define the role of biological agents in the treatment of ovarian cancer.

  10. Ovarian cancer mortality and industrial pollution.

    Science.gov (United States)

    García-Pérez, Javier; Lope, Virginia; López-Abente, Gonzalo; González-Sánchez, Mario; Fernández-Navarro, Pablo

    2015-10-01

    We investigated whether there might be excess ovarian cancer mortality among women residing near Spanish industries, according to different categories of industrial groups and toxic substances. An ecologic study was designed to examine ovarian cancer mortality at a municipal level (period 1997-2006). Population exposure to pollution was estimated by means of distance from town to facility. Using Poisson regression models, we assessed the relative risk of dying from ovarian cancer in zones around installations, and analyzed the effect of industrial groups and pollutant substances. Excess ovarian cancer mortality was detected in the vicinity of all sectors combined, and, principally, near refineries, fertilizers plants, glass production, paper production, food/beverage sector, waste treatment plants, pharmaceutical industry and ceramic. Insofar as substances were concerned, statistically significant associations were observed for installations releasing metals and polycyclic aromatic chemicals. These results support that residing near industries could be a risk factor for ovarian cancer mortality. PMID:26046426

  11. OVARIAN METASTASIS IN PATIENT WITH ENDOMETRIAL CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    ZHOU Feng-zhi; CHEN Yi-nan; ZHANG Guo-nan

    2005-01-01

    Objective: To study the clinical pathological characteristics of ovarian metastasis of endometrial carcinoma and the factors affecting prognosis. Methods: Retrospective analysis was made to the clinical pathological outcome of endometrial carcinoma patients receiving surgical treatment in our hospital from January 1990 to December 2002. Results:Among the 191 cases of endometrial carcinoma patients, 17 cases (8.9%) had ovarian metastasis and young patients were more likely to have ovarian metastasis. The multiple factor analysis showed that the independent risk factors of ovarian metastasis in endometrial carcinoma included the depth of myometrial invasion, lymph node metastasis and pathological types. Conclusion: Ovarian metastasis in patients with endometrial carcinoma is associated with poor prognosis, the depth of myometrial invasion, lymph node metastasis and histologic types are independent risk factors affecting the prognosis. For young patients at early stage of the disease, it should be prudent as to whether to retain the ovary.

  12. Genetic profiles distinguish different types of hereditary ovarian cancer

    DEFF Research Database (Denmark)

    Domanska, Katarina; Malander, Susanne; Staaf, Johan;

    2010-01-01

    Heredity represents the strongest risk factor for ovarian cancer with disease predisposing mutations identified in 15% of the tumors. With the aim to identify genetic classifiers for hereditary ovarian cancer, we profiled hereditary ovarian cancers linked to the hereditary breast and ovarian canc...

  13. Vasoactive intestinal peptide-induced expression of cytochrome P450 cholesterol side-chain cleavage and 17 alpha-hydroxylase enzyme activity in hen granulosa cells.

    Science.gov (United States)

    Johnson, A L; Li, Z; Gibney, J A; Malamed, S

    1994-08-01

    Experiments were conducted to determine whether vasoactive intestinal peptide (VIP) can regulate expression of cytochrome P450 side-chain cleavage (P450scc) and P450 17 alpha-hydroxylase (P450 17 alpha-OH) mRNA levels and enzyme activity in granulosa cells from nonhierarchal (6-8-mm) follicles. Initial studies demonstrated that immunoreactive VIP is localized within the theca (but not granulosa) layer of both resting (< 0.5-mm follicles) and 6-8-mm follicles, thus providing a potential paracrine mechanism of action for VIP. While short-term (3 h) incubation of granulosa cells with VIP (0.001-1.0 microM) failed to stimulate progesterone production from 6-8-mm follicle granulosa cells, a 4-h culture period in the presence of VIP resulted in increased cyclic AMP (cAMP) accumulation, and a 24-h culture period resulted in progesterone synthesis and increased P450scc mRNA levels; control levels of each endpoint measurement were not altered within the period observed. By contrast, culture with the growth factor transforming growth factor alpha (TGF alpha) in the presence of VIP (1 microM) prevented increases in P450scc mRNA levels and progesterone production. Similar effects of VIP and TGF alpha in the presence of VIP were demonstrated for P450 17 alpha-OH mRNA levels and enzyme activity. Finally, there was an additive effect of VIP (0.1 microM) plus recombinant human (rh) FSH (100 mIU) on the initiation of progesterone production in cultured 6-8-mm follicle granulosa cells compared to the addition of VIP or rhFSH alone.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Oncolytic reovirus against ovarian and colon cancer.

    Science.gov (United States)

    Hirasawa, Kensuke; Nishikawa, Sandra G; Norman, Kara L; Alain, Tommy; Kossakowska, Anna; Lee, Patrick W K

    2002-03-15

    Reovirus selectively replicates in and destroys cancer cells with an activated Ras signaling pathway. In this study, we evaluated the feasibility of using reovirus (serotype 3, strain Dearing) as an antihuman colon and ovarian cancer agent. In in vitro studies, reovirus infection in human colon and ovarian cell lines was assessed by cytopathic effect as detected by light microscopy, [(35)S]Methionine labeling of infected cells for viral protein synthesis and progeny virus production by plaque assay. We observed that reovirus efficiently infected all five human colon cancer cell lines (Caco-2, DLD-1, HCT-116, HT-29, and SW48) and four human ovarian cancer cell lines (MDAH2774, PA-1, SKOV3, and SW626) which were tested, but not a normal colon cell line (CCD-18Co) or a normal ovarian cell line (NOV-31). We also observed that the Ras activity in the human colon and ovarian cancer cell lines was elevated compared with that in normal colon and ovarian cell lines. In animal models, intraneoplastic as well as i.v. inoculation of reovirus resulted in significant regression of established s.c. human colon and ovarian tumors implanted at the hind flank. Histological studies revealed that reovirus infection in vivo was restricted to tumor cells, whereas the surrounding normal tissue remained uninfected. Additionally, in an i.p. human ovarian cancer xenograft model, inhibition of ascites tumor formation and the survival of animals treated with live reovirus was significantly greater than of control mice treated with UV-inactivated reovirus. Reovirus infection in ex vivo primary human ovarian tumor surgical samples was also confirmed, further demonstrating the potential of reovirus therapy. These results suggest that reovirus holds promise as a novel agent for human colon and ovarian cancer therapy. PMID:11912142

  15. OVARIAN CALCIFICATION MIMICKING VESICLE CALCULUS

    Directory of Open Access Journals (Sweden)

    Pallavi

    2013-04-01

    Full Text Available INTRODUCTION: Calcification in ovary is usually dystrophic in natu re, forming secondary to degeneration of the epithelium or in association wit h areas of necrosis. It may occur in cases of endometriosis [1] or in some ovarian tumor eg. Fibro thecoma [2] , Brenner’s tumor [3] , cavernous hemangioma [4] etc. Benign unilateral densely calcified ovary wit hout any association with tumor or endometriosis has not been reported previously. We report a case of heavily calcified left ovary which mimicked as vesicle calculus on X- ray leading to confusion in diagnosis.

  16. 出生早期使用二甲双胍对宫内高雄激素化仔鼠成年后卵巢CYP17的影响%Expression of CYP17 in ovarian tissue of adult rat model with hyperandrogenism in uterus and treatment by metformin in newborn

    Institute of Scientific and Technical Information of China (English)

    樊佳丽; 段涛; 周倩

    2012-01-01

    Objective:To construct polycystic ovary syndrome(PCOS) rat model by mater-nal exposure to excess testosterone,examine the CYP17 and metabolism in the rat models after trea-ted by metformin in newborn. Methods: Wistar female rats were randomly divided into model group and control group. On days 16~18 of pregnancy, wistar female rats were injected S. C. with testoster-one propionas 2. 5 mg or sesame oil daily for 3 consecutive days. Pregnant rats after delivery 2 days were gavaged by metformin 450mg/(kg·d) and saline for 14 consecutive days. Adult female off-springs were studied. Serum concentrations of sex hormones luteinizing hormone,Follicle-stimulating hormone,Testosterone,insulin were measured. CYP17 protein expression in ovary were determined by immunohistochemistry and Western blot. Result: ( 1) The female rats that were prenatally androg-enized had polycystic ovary. Serum levels of testosterone, luteinizing hormone were significantly higher. The insulin levels and Follicle-stimulating hormone had not changed. Western blot showed that the expression of CYP17 in model ovarian tissues were higher. (2) The prenatally androgenized female rats that were treated by metformin in newborn had normal ovary. Serum hormone levels and the expression of CYP17 returned to normal. Conclusion: Prenatally androgenized female rats exhibi-ted hyperandrogenism,high luteinizing hormone and polycystic ovary,which is coincident with the characteristics of human PCOS. Metformin by adjusting the serum hormone levels and ovarian CYP17 expression played a role in improve the clinical symptoms of prenatal androgen mice.%目的:使孕中期雌鼠暴露于高雄激素状态,观察其雌性子代在出生早期使用二甲双胍后,血清激素水平及卵巢组织中17a-羟化酶(CYP17)表达情况.方法:选择孕16~18天的Wistar雌性大鼠,在颈背部皮下注射丙酸睾丸酮,连续3天.孕鼠分娩后第2天予以二甲双胍灌胃,连续14天.雌仔鼠生长至成年后作为

  17. La pesquería mixta de las centollas Lithodes santolla y Paralomis granulosa (Anomura: Lithodidae) en Tierra del Fuego, Argentina The mixed fishery for the king crabs Lithodes santolla and Paralomis granulosa (Anomura: Lithodidae) in Tierra del Fuego, Argentina

    OpenAIRE

    Gustavo A Lovrich

    1997-01-01

    En el Canal Beagle (55ºS; 66ºW), los individuos de dos especies simpátridas de litódidos, la centolla Lithodes santolla y el centollón Paralomis granulosa aparecen frecuentemente juntos en las trampas y por ello su pesquería se denomina mixta. Las dos especies difieren en su potencial reproductivo y por tanto en la tasa de reposición de individuos a la población. L. santolla es de mayor tamaño (máximo 180 mm de largo de caparazón, Lc y hasta 6 kg de peso), tiene un tiempo generacional de 6 añ...

  18. Ovarian cancer after in vitro fertilization

    Directory of Open Access Journals (Sweden)

    Milenković Vera

    2004-01-01

    Full Text Available There is serious concern about cancer risk in women undergoing ovarian stimulation treatment for infertility and long-term safety of these procedures. Association between fertility drugs and ovarian cancer is still controversial. A 30-year-old woman was referred to our institution with the initial diagnosis of an adnexal tumor after in vitro fertilization. Her history revealed adnexectomy for mucinous cystadenofibroma of the left ovary eight years ago, and cystectomy due to cystadenoma of the right ovary three years ago. At admission, the most remarkable findings were high temperature and elevated white blood cell count and erythrocyte sedimentation rate. Broad spectrum antibiotic treatment was initiated. Six days after admission, the patient was feverish, with temperature up to 38°C, and evident signs of the acute abdomen. Immediate laparotomy was performed and multilocular right adnexal tumor 150x130x100 millimeters in size was identified. The right salpingo-oophorectomy was carried out. Pathological diagnosis was mucinous ovarian adenocarcinoma. Eighteen days later, radical surgery was performed. After the surgery, chemotherapy was applied. There is an urgent need for clear interpretation of the association between fertility drugs and subsequent higher ovarian cancer risk. Lacking conclusive evidence, an increased risk of ovarian cancer has been reported and more recently disputed. Higher ovarian cancer risk may be serious and even life-threatening complication for women undergoing ovarian stimulation.

  19. Obesity and risk of ovarian cancer subtypes

    DEFF Research Database (Denmark)

    Olsen, Catherine M; Nagle, Christina M; Whiteman, David C;

    2013-01-01

    Whilst previous studies have reported that higher BMI increases a woman's risk of developing ovarian cancer, associations for the different histological subtypes have not been well defined. As the prevalence of obesity has increased dramatically, and classification of ovarian histology has improv......, it does not increase risk of high-grade invasive serous cancers, and reducing BMI is therefore unlikely to prevent the majority of ovarian cancer deaths. Other modifiable factors must be identified to control this disease.......Whilst previous studies have reported that higher BMI increases a woman's risk of developing ovarian cancer, associations for the different histological subtypes have not been well defined. As the prevalence of obesity has increased dramatically, and classification of ovarian histology has improved...... in the last decade, we sought to examine the association in a pooled analysis of recent studies participating in the Ovarian Cancer Association Consortium. We evaluated the association between BMI (recent, maximum and in young adulthood) and ovarian cancer risk using original data from 15 case...

  20. Thrombosis following ovarian hyperstimulation syndrome.

    Science.gov (United States)

    Kasum, Miro; Danolić, Damir; Orešković, Slavko; Ježek, Davor; Beketić-Orešković, Lidija; Pekez, Marijeta

    2014-11-01

    The aim of this review is to analyse the pathophysiology and complications of thrombosis in conjuction with ovarian hyperstimulation syndrome (OHSS) following ovulation induction and to suggest practical guidelines usefull for the prevention and treatment. Although the incidence of thrombosis varies from 0.2% among in vitro fertilization (IVF) cycles and up to 10% for severe cases of the syndrome, it represents the most dangerous complication of OHSS. Different changes in haemostatic markers have been found to create a state of hypercoagulability, but no single standard test is available to estimate the state of thrombosis. The role of markers for thrombophilia is controversial. Thromboses are mostly venous (67-75%) involving upper limbs and neck, then arterial (25-33%) which are mainly intracerebral. The predominant sites of venous thromboembolism in the upper part of the body may be explained by higher concentrations of estrogens drained through lymphatic ducts from ascites and by compression of rudimentary branchyal cysts. Once early diagnosis is established, it is crucial to use an anticoagulant treatment with heparin proceeded with thromboprophylaxis. However, identification of patients at risk and preventive measures of OHSS are the best means in reducing the risk of thrombosis after ovarian stimulation.

  1. Induction of chemokines and prostaglandin synthesis pathways in luteinized human granulosa cells: potential role of luteotropin withdrawal and prostaglandin F2α in regression of the human corpus luteum.

    Science.gov (United States)

    Luo, Wenxiang; Salih, Sana M; Bormann, Charles L; Wiltbank, Milo C

    2015-12-01

    Our objective was to determine the effects of prostaglandin F2α (PGF2α) and withdrawal of luteotropic stimulants (forskolin or hCG) on expression of chemokines and prostaglandin-endoperoxide synthase 2 (PTGS2) in luteinized human granulosa cells. Human granulosa cells were collected from 12 women undergoing oocyte retrieval and were luteinized in vitro with forskolin or hCG. In first experiment, granulosa-lutein cells were treated with PGF2α, the primary luteolytic hormone in most species. In second experiment, granulosa cells that had been luteinized for 8 d had luteotropins withdrawn for 1, 2, or 3 d. Treatment with PGF2α induced mRNA for chemokine (c-x-c motif) ligand 2 (CXCL2) and CXC ligand 8 (CXCL8; also known as interleukin-8) in granulosa cells luteinized for 8 d but not in cells that were only luteinized for 2 d. Similarly, luteinization of human granulosa cells for 8 d with forskolin or hCG followed by withdrawal of luteotropic stimulants, not only decreased P4 production, but also increased mRNA concentrations for CXCL8, CXCL-2 (after forskolin withdrawal), and PTGS2. These results provide evidence for two key steps in differentiation of luteolytic capability in human granulosa cells. During 8 d of luteinization, granulosa cells acquire the ability to respond to luteolytic factors, such as PGF2α, with induction of genes involved in immune function and PG synthesis. Finally, a decline in luteotropic stimuli triggers similar pathways leading to induction of PTGS2 and possibly intraluteal PGF2α production, chemokine expression, leukocyte infiltration and activation, and ultimately luteal regression. PMID:26679166

  2. Obesity and risk of ovarian cancer subtypes: evidence from the Ovarian Cancer Association Consortium

    OpenAIRE

    Olsen, C. M.; Nagle, C. M.; Whiteman, D C; Ness, R; C. L. Pearce; Pike, M. C.; Rossing, M A; Terry, Kathryn Lynne; Wu, A. H.; Risch, H A; Yu, H.; Doherty, J. A.; Chang-Claude, J; Hein, R.; Nickels, S

    2013-01-01

    Whilst previous studies have reported that higher body-mass index (BMI) increases a woman’s risk of developing ovarian cancer, associations for the different histological subtypes have not been well defined. As the prevalence of obesity has increased dramatically, and classification of ovarian histology has improved in the last decade, we sought to examine the association in a pooled analysis of recent studies participating in the Ovarian Cancer Association Consortium. We ev...

  3. Bilateral ovarian mixed epithelial adenocarcinoma in a postmenopausal woman with unilateral ovarian yolk sac tumor component

    OpenAIRE

    Qin CHEN; Chen, Xiaoduan

    2014-01-01

    Ovarian yolk sac tumors (YSTs) usually occur in the young women and have been rarely documented in perimenopausal and postmenopausal women. The different age distribution supposes their complex nomenclature and histogenesis. We report a case of bilateral ovarian epithelial carcinoma with right ovarian YST component in a postmenopausal woman. The patient was treated by surgery and adjuvant combination chemotherapy of taxol and carboplatin for 6 courses and has been clinically free of tumor for...

  4. Rethinking ovarian cancer II: reducing mortality from high-grade serous ovarian cancer.

    Science.gov (United States)

    Bowtell, David D; Böhm, Steffen; Ahmed, Ahmed A; Aspuria, Paul-Joseph; Bast, Robert C; Beral, Valerie; Berek, Jonathan S; Birrer, Michael J; Blagden, Sarah; Bookman, Michael A; Brenton, James D; Chiappinelli, Katherine B; Martins, Filipe Correia; Coukos, George; Drapkin, Ronny; Edmondson, Richard; Fotopoulou, Christina; Gabra, Hani; Galon, Jérôme; Gourley, Charlie; Heong, Valerie; Huntsman, David G; Iwanicki, Marcin; Karlan, Beth Y; Kaye, Allyson; Lengyel, Ernst; Levine, Douglas A; Lu, Karen H; McNeish, Iain A; Menon, Usha; Narod, Steven A; Nelson, Brad H; Nephew, Kenneth P; Pharoah, Paul; Powell, Daniel J; Ramos, Pilar; Romero, Iris L; Scott, Clare L; Sood, Anil K; Stronach, Euan A; Balkwill, Frances R

    2015-11-01

    High-grade serous ovarian cancer (HGSOC) accounts for 70-80% of ovarian cancer deaths, and overall survival has not changed significantly for several decades. In this Opinion article, we outline a set of research priorities that we believe will reduce incidence and improve outcomes for women with this disease. This 'roadmap' for HGSOC was determined after extensive discussions at an Ovarian Cancer Action meeting in January 2015. PMID:26493647

  5. CD9 Expression by Human Granulosa Cells and Platelets as a Predictor of Fertilization Success during IVF

    Directory of Open Access Journals (Sweden)

    Carolyn R. Jaslow

    2010-01-01

    Full Text Available Objective. To determine whether CD9 expression on human granulosa cells (GCs and platelets could predict the success of conventional fertilization of human oocytes during in vitro fertilization (IVF. Methods. Thirty women undergoing IVF for nonmale factor infertility participated. Platelets from venous blood and GCs separated from retrieved oocytes were prepared for immunofluorescence. Flow cytometry quantified the percent of GCs expressing CD9, and CD9 surface density on GCs and platelets. Fertilization rate was determined for the total number of oocytes, and the number of mature oocytes per patient. Correlations tested for significant relationships (P<.05 between fertilization rates and CD9 expression. Results. CD9 surface density on human GCs is inversely correlated with fertilization rate of oocytes (P=.04, but the relationship was weak. Conclusion. More studies are needed to determine if CD9 expression on GCs would be useful for predicting conventional fertilization success during IVF.

  6. Effects of temperature on embryonic and early larval growth and development in the rough-skinned newt (Taricha granulosa).

    Science.gov (United States)

    Smith, Geoffrey D; Hopkins, Gareth R; Mohammadi, Shabnam; M Skinner, Heather; Hansen, Tyler; Brodie, Edmund D; French, Susannah S

    2015-07-01

    We investigated the effects of temperature on the growth and development of embryonic and early larval stages of a western North American amphibian, the rough-skinned newt (Taricha granulosa). We assigned newt eggs to different temperatures (7, 14, or 21°C); after hatching, we re-assigned the newt larvae into the three different temperatures. Over the course of three to four weeks, we measured total length and developmental stage of the larvae. Our results indicated a strong positive relationship over time between temperature and both length and developmental stage. Importantly, individuals assigned to cooler embryonic temperatures did not achieve the larval sizes of individuals from the warmer embryonic treatments, regardless of larval temperature. Our investigation of growth and development at different temperatures demonstrates carry-over effects and provides a more comprehensive understanding of how organisms respond to temperature changes during early development. PMID:25965021

  7. Ovarian tuberculosis mimicking a malignant tumour

    Directory of Open Access Journals (Sweden)

    Eric Yebouet

    2015-01-01

    Full Text Available There has been reported increased incidence of ovarian tuberculosis in the tropics since the advent of HIV/AIDS disease. We report a case of bilateral ovarian tuberculosis associated with a single right kidney of uncertain origin in an immunocompetent 15-year-old generally healthy-looking girl. Abdominopelvic scan was equivocal about the diagnosis of the lesion as it failed to differentiate it from malignancy. Tuberculin and histopathology were necessary to confirm the diagnosis of ovarian tuberculosis. Antituberculous medical therapy successfully resolved the disease.

  8. Premature ovarian failure: morphological and ultrastructural aspects.

    Science.gov (United States)

    Haidar, M A; Baracat, E C; Simões, M J; Focchi, G R; Evêncio Neto, J; de Lima, G R

    1994-01-01

    The authors documented by means of light and transmission electron microscopy that the ovaries of women with premature ovarian failure (POF) displayed dense connective tissue and rare corpora albicantia. Eight of the ten studied cases did not present ovarian follicles; in two cases, it was verified the presence of ovarian follicles, atypical primordial follicles and in one case, a corpus luteum was identified (after stimulation with exogenous gonadotrophin). Regarding the ultrastructural analysis, it was noted that the fibroblasts were united one to each other by cellular prolongations that formed a woof, constituting a cellular syncicius. PMID:7610321

  9. Changes in Brain Function in Patients With Stage I, Stage II, Stage III, or Stage IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer Who Are Receiving Chemotherapy

    Science.gov (United States)

    2016-02-09

    Cognitive Side Effects of Cancer Therapy; Malignant Ovarian Epithelial Tumor; Malignant Ovarian Mixed Epithelial Tumor; Ovarian Brenner Tumor; Ovarian Carcinosarcoma; Ovarian Choriocarcinoma; Ovarian Clear Cell Cystadenocarcinoma; Ovarian Dysgerminoma; Ovarian Embryonal Carcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mixed Germ Cell Tumor; Ovarian Mucinous Cystadenocarcinoma; Ovarian Polyembryoma; Ovarian Sarcoma; Ovarian Serous Cystadenocarcinoma; Ovarian Teratoma; Ovarian Yolk Sac Tumor; Stage I Ovarian Cancer; Stage IA Fallopian Tube Cancer; Stage IA Ovarian Cancer; Stage IA Ovarian Germ Cell Tumor; Stage IB Fallopian Tube Cancer; Stage IB Ovarian Cancer; Stage IB Ovarian Germ Cell Tumor; Stage IC Fallopian Tube Cancer; Stage IC Ovarian Cancer; Stage IC Ovarian Germ Cell Tumor; Stage II Ovarian Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIA Ovarian Germ Cell Tumor; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIB Ovarian Germ Cell Tumor; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIC Ovarian Germ Cell Tumor; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Ovarian Germ Cell Tumor; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Ovarian Germ Cell Tumor; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Ovarian Germ Cell Tumor; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Ovarian Germ Cell Tumor; Stage IV Primary Peritoneal Cancer; Undifferentiated Ovarian Carcinoma

  10. PAX2 Expression in Low Malignant Potential Ovarian Tumors and Low-Grade Ovarian Serous Carcinomas

    Science.gov (United States)

    Tung, Celestine S.; Mok, Samuel C.; Tsang, Yvonne T.M.; Zu, Zhifei; Song, Huijuan; Liu, Jinsong; Deavers, Michael; Malpica, Anais; Wolf, Judith K.; Lu, Karen H.; Gershenson, David M.; Wong, Kwong-Kwok

    2009-01-01

    Ovarian tumors of low-malignant potential and low-grade ovarian serous carcinomas are thought to represent different stages on a tumorigenic continuum and to develop along pathways distinct from high-grade ovarian serous carcinoma. We performed gene expression profiling on 3 normal human ovarian surface epithelia samples, and 10 low-grade and 10 high-grade ovarian serous carcinomas. Analysis of gene expression profiles of these samples has identified 80 genes up-regulated and 232 genes down-regulated in low-grade ovarian serous carcinomas. PAX2 was found to be one of the most up-regulated genes in low-grade ovarian serous carcinoma. The up-regulation of PAX2 was validated by real-time quantitative RT-PCR, Western blot and immunohistochemical analyses. Real-time RT-PCR demonstrated a statistically significant difference in PAX2 mRNA expression (expressed as fold change in comparison to normal human ovarian surface epithelia) among ovarian tumors of low-malignant potential (1837.38, N=8), low-grade (183.12, N=17), and high-grade (3.72, N=23) carcinoma samples (p=0.015). Western blot analysis revealed strong PAX2 expression in ovarian tumors of low-malignant potential (67%, N=3) and low-grade carcinoma samples (50%, N=10) but no PAX2 protein expression in high-grade carcinomas (0%, N=10). Using immunohistochemistry, tumors of low-malignant potential (59%, N=17) and low-grade carcinoma (63%, N=16) samples expressed significantly stronger nuclear staining than high-grade ovarian carcinoma samples (9.1%, N=263). Furthermore, consistent with previous immunohistochemical findings, PAX2 expression was found to be expressed in the epithelial cells of fallopian tubes but not in normal ovarian surface epithelial cells. Our findings further support the two-tiered hypothesis that tumors of low-malignant potential and low-grade ovarian serous carcinoma are on a continuum and are distinct from high-grade ovarian carcinomas. Additionally, the absence of PAX2 expression in normal

  11. High salinity tolerance of the Red Sea coral Fungia granulosa under desalination concentrate discharge conditions: an in situ photophysiology experiment

    KAUST Repository

    Van Der Merwe, Riaan

    2014-11-10

    Seawater reverse osmosis desalination concentrate may have chronic and/or acute impacts on the marine ecosystems in the near-field area of the discharge. Environmental impact of the desalination plant discharge is supposedly site- and volumetric- specific, and also depends on the salinity tolerance of the organisms inhabiting the water column in and around a discharge environment. Scientific studies that aim to understand possible impacts of elevated salinity levels are important to assess detrimental effects to organisms, especially for species with no mechanism of osmoregulation, e.g., presumably corals. Previous studies on corals indicate sensitivity toward hypo- and hyper-saline environments with small changes in salinity already affecting coral physiology. In order to evaluate sensitivity of Red Sea corals to increased salinity levels, we conducted a long-term (29 days) in situ salinity tolerance transect study at an offshore seawater reverse osmosis (SWRO) discharge on the coral Fungia granulosa. While we measured a pronounced increase in salinity and temperature at the direct outlet of the discharge structure, effects were indistinguishable from the surrounding environment at a distance of 5 m. Interestingly, corals were not affected by varying salinity levels as indicated by measurements of the photosynthetic efficiency. Similarly, cultured coral symbionts of the genus Symbiodinium displayed remarkable tolerance levels in regard to hypo- and hypersaline treatments. Our data suggest that increased salinity and temperature levels from discharge outlets wear off quickly in the surrounding environment. Furthermore, F. granulosa seem to tolerate levels of salinity that are distinctively higher than reported for other corals previously. It remains to be determined whether Red Sea corals in general display increased salinity tolerance, and whether this is related to prevailing levels of high(er) salinity in the Red Sea in comparison to other oceans.

  12. High salinity tolerance of the Red Sea coral Fungia granulosa under desalination concentrate discharge conditions: An in situ photophysiology experiment

    Directory of Open Access Journals (Sweden)

    Riaan evan der Merwe

    2014-11-01

    Full Text Available Seawater reverse osmosis desalination concentrate may have chronic/acute impacts on the marine ecosystems in the near-field area of the discharge. Environmental impact of the desalination plant discharge is supposedly site- and volumetric specific, and also depends on the salinity tolerance of the organisms inhabiting the water column in and around a discharge environment. Scientific studies that aim to understand possible impacts of elevated salinity levels are important to assess detrimental effects to organisms, especially for species with no mechanism of osmoregulation, e.g. presumably corals. Previous studies on corals indicate sensitivity towards hypo- and hyper-saline environments with small changes in salinity already affecting coral physiology. In order to evaluate sensitivity of Red Sea corals to increase salinity levels, we conducted a long-term (29 days in situ salinity tolerance transect study at an offshore seawater reverse osmosis discharge on the coral Fungia granulosa. While we measured a pronounced increase in salinity and temperature at the direct outlet of the discharge structure, effects were indistinguishable from the surrounding environment at a distance of 5 m. Interestingly, corals were not affected by varying salinity levels as indicated by measurement of the photosynthetic efficiency. Similarly, cultured coral symbionts of the genus Symbiodinium displayed remarkable tolerance levels in regard to hypo- and hypersaline treatments.Our data suggest that increased salinity and temperature levels from discharge outlets wear off quickly in the surrounding environment. Furthermore, Fungia granulosa seem to tolerate levels of salinity that are distinctively higher than reported for other corals previously. It remains to be determined whether Red Sea corals in general display increased salinity tolerance, and whether this is related to prevailing levels of high(er salinity in the Red Sea in comparison to other oceans.

  13. Social Recognition Memory: Influence of Age, Sex, and Ovarian Hormonal Status

    OpenAIRE

    Markham, Julie A.; Juraska, Janice M.

    2007-01-01

    Social recognition memory underlies many forms of rodent interaction and can be easily tested in the laboratory. Sex differences in aspects of this memory have been reported among young adults, and some studies indicate an age-related decline among male rats. In contrast, neither the impact of natural fluctuations in ovarian hormones nor the performance of aged female rats on social recognition memory has been previously evaluated. In experiments 1 and 2, the social recognition memory of youn...

  14. Influence of FSH and hCG on the resumption of meiosis of bovine oocytes surrounded by cumulus cells connected to membrana granulosa.

    Science.gov (United States)

    van Tol, H T; van Eijk, M J; Mummery, C L; van den Hurk, R; Bevers, M M

    1996-10-01

    Cumulus oocyte complexes (COCs) and cumulus oocyte complexes connected to a piece of the membrane granulosa (COCGs) were isolated from bovine antral follicles with a diameter of 2 to 8 mm. After culture of COCGs without gonadotrophic hormones for 22 hr approximately 50% of the oocytes were still in the germinal vesicle (GV) stage. Histology of the COCGs showed that the pieces of the membrana granulosa were free of thecal cells and parts of the basal membrane. This indicates that the membrana granulosa solely inhibits the progression of meiosis. To investigate the effect of gonadotropins on the resumption of meiosis of oocytes from small and medium sized antral follicles, COCs and COCGs were cultured with or without rec-hFSH or hCG. Addition of 0.05 IU rec-hFSH to the culture medium of COCGs resulted in germinal vesicle breakdown in 97.8% of the oocytes compared to 46% in the control group, and an increase of the diameter of the COCs (479 microns vs. 240 microns in the control group). Addition of 0.05 IU hCG to the culture medium had no effect on nuclear maturation (47.2% GV vs. 48.5% GV in the control group) nor on cumulus expansion (246 microns vs. 240 microns in the control group). RT-PCR on cDNA of the follicular wall, cumulus cells, granulosa cells, COCs, and oocytes revealed that mRNA for FSH receptor was present in all cell types except oocytes. mRNA of the LH receptor was detected exclusively in thecal cells. Nucleotide sequence analysis and alignment of the cloned PCR products showed the presence of two isoforms of the FSH receptor mRNA and two isoforms of the LH receptor mRNA. It is concluded that, in vitro, resumption of meiosis of oocytes, originating from small and medium sized antral follicles and meiotically arrested by the membrana granulosa, is triggered by FSH and not by LH. This is supported by the fact that receptors for FSH, but not for LH, are transcribed in the cumulus and granulosa cells of these follicles. PMID:8914080

  15. Serum GDF-8 levels change dynamically during controlled ovarian hyperstimulation in patients undergoing IVF/ICSI-ET

    Science.gov (United States)

    Fang, Lanlan; Yu, Yiping; Zhang, Ruizhe; He, Jingyan; Sun, Ying-Pu

    2016-01-01

    Growth differentiation factor-8 (GDF-8) is found in the human serum, follicular fluid and granulosa cells. Our previous studies have shown that the human cumulus expansion and steroidogenesis can be regulated by GDF-8. However, thus far, the expression profile of GDF-8 in serum and whether the level of serum GDF-8 influences pregnancy results for patients treated with in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET) is totally unknown. In this study, we showed that GDF-8 had a dynamic trend during controlled ovarian hyperstimulation (COH) procedure. On human chorionic gonadotropin (hCG) administration day, patients with a GDF-8 level higher than 4.7 ng/ml had lower progesterone levels and a higher pregnancy rate. From hCG day to oocyte pick-up day, patients with a GDF-8 decrease greater than 1.3 ng/ml had a higher progesterone increase and a higher pregnancy rate. Importantly, the levels of GDF-8 were negatively correlated with progesterone levels. Our findings provide evidences that GDF-8 plays an important role in ensuring successful pregnancy by regulating progesterone levels. PMID:27329327

  16. Novel Treatment Shrinks Ovarian Tumors in Mice

    Science.gov (United States)

    Researchers have developed a new approach for treating tumors that express mutant versions of the p53 protein, which are present in more than half of all cancers, including an aggressive and common subtype of ovarian cancer.

  17. Hormone therapy and different ovarian cancers

    DEFF Research Database (Denmark)

    Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms;

    2012-01-01

    Postmenopausal hormone therapy use increases the risk of ovarian cancer. In the present study, the authors examined the risks of different histologic types of ovarian cancer associated with hormone therapy. Using Danish national registers, the authors identified 909,946 women who were followed from...... 1995-2005. The women were 50-79 years of age and had no prior hormone-sensitive cancers or bilateral oophorectomy. Hormone therapy prescription data were obtained from the National Register of Medicinal Product Statistics. The National Cancer and Pathology Register provided data on ovarian cancers......, including information about tumor histology. The authors performed Poisson regression analyses that included hormone exposures and confounders as time-dependent covariates. In an average of 8.0 years of follow up, 2,681 cases of epithelial ovarian cancer were detected. Compared with never users, women...

  18. Predictive and therapeutic markers in ovarian cancer

    Science.gov (United States)

    Gray, Joe W.; Guan, Yinghui; Kuo, Wen-Lin; Fridlyand, Jane; Mills, Gordon B.

    2013-03-26

    Cancer markers may be developed to detect diseases characterized by increased expression of apoptosis-suppressing genes, such as aggressive cancers. Genes in the human chromosomal regions, 8q24, 11q13, 20q11-q13, were found to be amplified indicating in vivo drug resistance in diseases such as ovarian cancer. Diagnosis and assessment of amplification levels certain genes shown to be amplified, including PVT1, can be useful in prediction of poor outcome of patient's response and drug resistance in ovarian cancer patients with low survival rates. Certain genes were found to be high priority therapeutic targets by the identification of recurrent aberrations involving genome sequence, copy number and/or gene expression are associated with reduced survival duration in certain diseases and cancers, specifically ovarian cancer. Therapeutics to inhibit amplification and inhibitors of one of these genes, PVT1, target drug resistance in ovarian cancer patients with low survival rates is described.

  19. Olaparib in the management of ovarian cancer

    Directory of Open Access Journals (Sweden)

    Bixel K

    2015-08-01

    Full Text Available Kristin Bixel,1 John L Hays2 1Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, 2Department of Hematology Oncology, Ohio State University, Columbus, OH, USAAbstract: Alterations in the homologous repair pathway are thought to occur in 30%–50% of epithelial ovarian cancers. Cells deficient in homologous recombination rely on alternative pathways for DNA repair in order to survive, thereby providing a potential target for therapy. Olaparib, a poly(ADP-ribose polymerase (PARP inhibitor, capitalizes on this concept and is the first drug in its class approved for patients with ovarian cancer. This review article will provide an overview of the BRCA genes and homologous recombination, the role of PARP in DNA repair and the biological rationale for the use of PARP inhibitors as cancer therapy, and ultimately will focus on the use of olaparib in the management of ovarian cancer.Keywords: olaparib, ovarian cancer, PARP inhibitor

  20. Ovarian cancer in an interdisciplinary context

    DEFF Research Database (Denmark)

    Seibæk, Lene

    quality of treatment.   Patients/ Methods We developed an interdisciplinary programme including patient data from the records of doctors, nurses, anaesthetists and observations. This programme was applied on a population of 65 women with ovarian malignancies. Subsequently analyses were performed...

  1. Ovarian cancer in an interdisciplinary context

    DEFF Research Database (Denmark)

    Seibæk, Lene

      Introduction Worldwide, ovarian cancer is the sixth most common type of cancer, with more than 200,000 new cases each year and 125,000 related deaths. During the last decade, centralization and standardisation of surgical treatment have proven to be important tools in ovarian cancer to improve...... quality and survival. However, treatment efforts must be combined with high quality care, psychosocial support and organisational improvements.   Objectives The aim of this study was to evaluate an optimal debulking surgery programme in ovarian cancer, and subsequently develop a method of monitoring...... care resources and in future research. By using the interdisciplinary approach, women with ovarian cancer can benefit from a coherent and collaborative health care system.  ...

  2. Genetic and molecular changes in ovarian cancer

    Science.gov (United States)

    Hollis, Robert L; Gourley, Charlie

    2016-01-01

    Epithelial ovarian cancer represents the most lethal gynecological malignancy in the developed world, and can be divided into five main histological subtypes: high grade serous, endometrioid, clear cell, mucinous and low grade serous. These subtypes represent distinct disease entities, both clinically and at the molecular level. Molecular analysis has revealed significant genetic heterogeneity in ovarian cancer, particularly within the high grade serous subtype. As such, this subtype has been the focus of much research effort to date, revealing molecular subgroups at both the genomic and transcriptomic level that have clinical implications. However, stratification of ovarian cancer patients based on the underlying biology of their disease remains in its infancy. Here, we summarize the molecular changes that characterize the five main ovarian cancer subtypes, highlight potential opportunities for targeted therapeutic intervention and outline priorities for future research.

  3. Axillary node metastasis from primary ovarian carcinoma

    Directory of Open Access Journals (Sweden)

    Trupti S Patel

    2014-01-01

    Full Text Available Metastasization and distinction from mammary carcinoma is of great clinical importance because of different treatment modalities. Here, we discuss a case of stage IIIC ovarian serous carcinoma, presenting with bilateral axillary nodes metastasis after 25 months interval of its initial presentation. Increased serum CA-125 level caused clinical suspicion. Computed tomography scan of abdomen and pelvis showed no residual disease or any abdominal lymphadenopathy. Mammography of both breast were normal. Bilateral axillary nodes were noted. Guided fine needle aspiration cytology (FNAC and biopsy of ovarian carcinoma to axillary node is a rare event. Its recogn done. Cytomorphology revealed poorly differentiated carcinoma, compatible to that of primary ovarian tumor. Thus, metastatic carcinoma to axillary node from ovary was confirmed. This case illustrates a rare metastatic presentation of ovarian carcinoma and unequivocal role of FNAC to provide rapid diagnosis and preferred to be first line diagnostic procedure.

  4. Neoadjuvant chemotherapy as ovarian cancer treatment

    DEFF Research Database (Denmark)

    Fagö-Olsen, Carsten L; Ottesen, Bent; Kehlet, Henrik;

    2012-01-01

    INTRODUCTION: The traditional first-line treatment for patients with advanced ovarian cancer with primary debulking surgery (PDS) and adjuvant chemotherapy is controversial as some authors report a potential benefit from the alternative treatment with neoadjuvant chemotherapy (NACT) and interval...

  5. Ovarian cancer after in vitro fertilization

    OpenAIRE

    Milenković Vera; Sparić Radmila; Dokić Milan D.; Petković Spasoje; Atanacković Jasmina

    2004-01-01

    There is serious concern about cancer risk in women undergoing ovarian stimulation treatment for infertility and long-term safety of these procedures. Association between fertility drugs and ovarian cancer is still controversial. A 30-year-old woman was referred to our institution with the initial diagnosis of an adnexal tumor after in vitro fertilization. Her history revealed adnexectomy for mucinous cystadenofibroma of the left ovary eight years ago, and cystectomy due to cystadenoma of the...

  6. Repopulation of Ovarian Cancer Cells After Chemotherapy

    OpenAIRE

    Telleria, Carlos M.

    2013-01-01

    The high mortality rate caused by ovarian cancer has not changed for the past thirty years. Although most patients diagnosed with this disease respond to cytoreductive surgery and platinum-based chemotherapy and undergo remission, foci of cells almost always escape therapy, manage to survive, and acquire the capacity to repopulate the tumor. Repopulation of ovarian cancer cells that escape front-line chemotherapy, however, is a poorly understood phenomenon. Here I analyze cancer-initiating ce...

  7. Targeted Therapies in Epithelial Ovarian Cancer

    OpenAIRE

    Jurjees Hasan; Loaie El-Helw; Emma Dean

    2010-01-01

    Molecularly targeted therapy is relatively new to ovarian cancer despite the unquestionable success with these agents in other solid tumours such as breast and colorectal cancer. Advanced ovarian cancer is chemosensitive and patients can survive several years on treatment. However chemotherapy diminishes in efficacy over time whilst toxicities persist. Newer biological agents that target explicit molecular pathways and lack specific chemotherapy toxicities such as myelosuppression offer the a...

  8. HEALTHY EATING INDEX AND OVARIAN CANCER RISK

    OpenAIRE

    Chandran, Urmila; Elisa V Bandera; Williams-King, Melony G.; Paddock, Lisa E.; Rodriguez-Rodriguez, Lorna; Lu, Shou-En; Faulkner, Shameka; Pulick, Katherine; Olson, Sara H.

    2011-01-01

    The evidence for a role of diet on ovarian cancer prevention remains inconclusive. While many studies have evaluated individual foods and food groups, the evaluation of a comprehensive dietary quality index for predicting cancer risk has received little attention. This study investigates the association between the Healthy Eating Index (HEI), which reflects adherence to the current USDA Dietary Guidelines for Americans, and ovarian cancer risk in a population-based case-control study in New J...

  9. Ovarian cystadenofibroma: A masquerader of malignancy

    OpenAIRE

    Wasnik Ashish; Elsayes Khaled

    2010-01-01

    Ovarian cystadenofibroma is a relatively rare benign ovarian tumor that contains both epithelial and fibrous stromal components. The appearance of cystadenofibroma on imaging is often complex; cystic- to solid-appearing masses may be visualized and it often resembles a malignant tumor. Owing to the fibrous component of this tumor, MRI shows low-signal intensity on T2W images. This finding may help a radiologist make a preoperative diagnosis of this tumor and thus perhaps avoid aggressive surg...

  10. ROLE OF IMMUNOHISTOCHEMISTRY IN OVARIAN TUMORS

    OpenAIRE

    Lubna; Amita; Asha,; Chayanika; Sanjay; Rahul K.; Kiran

    2014-01-01

    BACKGROUND: Ovarian tumors are characterized by marked heterogeneity in their clinical presentation, so an accurate histopathological diagnosis is needed. Immunohistochemistry is helpful in vast number of cases where the morphology and clinical data alone do not allow definite diagnosis of tumor present in tissue sections. AIMS: 1. To evaluate the role of immune- histochemistry in classification and histogenesis of ovarian tumours and in resolving diagnostic dilemma in clo...

  11. Secondary ovarian tumors: Evaluation of 44 cases

    Directory of Open Access Journals (Sweden)

    Sevgiye KAÇAR ÖZKARA

    2007-09-01

    Full Text Available Secondary ovarian tumors compose 3-8% of all, and 10-30% of malignant ovarian tumors. Histopathological features of SOT diagnosed in our department in 10-year period are discussed. Macroscopical, microscopical, immunohistochemical and cytopathological features of secondary ovarian tumors diagnosed between 1997- 2006 were re-evaluated. Additional histochemical and immunohistochemical studies were applied to find the primaries. Data was statistically evaluated. Totally, 44 secondary ovarian tumors had been diagnosed within this period. The mean age of the patients was 52.9 years; the mean tumor diameter was 103.7 mm.The primary was gastrointestinal system in 50% of the cases. Ten of them (22.7% were metastases of signet ring cell carcinoma of stomach (Kruckenberg tumor while 9 cases (20.5% were from colorectal and three (6.8% were from appendiceal adenocarcinomas. 27.3% of our cases were originated from genital tract. Synchronous endometrioid adenocarcinomas of corpus uteri and ovary were seen in six cases (13.6%. Ovarian involvement of serous carcinomas of corpus uteri was seen in five (11.4% cases. Ovarian metastases of breast carcinoma in four cases (9.1% were seen while the ovarian involvement of adrenal cortical and tubal carcinomas was observed in one case, each. The primary was peritoneal surface in five (11.4% of the cases. Tumors were bilateral in 65.9% of the cases, and there was statistically significant correlation between the bilaterality rate of the tumors and the primary (p=0.015.The more precise diagnosis of secondary ovarian tumors could be reached by evaluation of clinical, surgical, macroscopical, microscopical, cytopathological and immunohistochemical findings together.

  12. Ovarian cancer screening in the general population.

    OpenAIRE

    Menon, U

    2007-01-01

    Despite significant improvements in therapy, ovarian cancer continues to be a leading cause of death amongst women with gynaecological malignancies. Advanced stage at diagnosis is thought to be a major contributor to mortality. Hence, there is considerable interest in early detection through screening. In the 1990s, Professor Jacobs pioneered the development of a multimodal ovarian cancer screening (OCS) strategy using serum CA125 as the first line screen and pelvic ultrasound as the second l...

  13. Rethinking ovarian cancer: recommendations for improving outcomes.

    Science.gov (United States)

    Vaughan, Sebastian; Coward, Jermaine I; Bast, Robert C; Berchuck, Andy; Berek, Jonathan S; Brenton, James D; Coukos, George; Crum, Christopher C; Drapkin, Ronny; Etemadmoghadam, Dariush; Friedlander, Michael; Gabra, Hani; Kaye, Stan B; Lord, Chris J; Lengyel, Ernst; Levine, Douglas A; McNeish, Iain A; Menon, Usha; Mills, Gordon B; Nephew, Kenneth P; Oza, Amit M; Sood, Anil K; Stronach, Euan A; Walczak, Henning; Bowtell, David D; Balkwill, Frances R

    2011-10-01

    There have been major advances in our understanding of the cellular and molecular biology of the human malignancies that are collectively referred to as ovarian cancer. At a recent Helene Harris Memorial Trust meeting, an international group of researchers considered actions that should be taken to improve the outcome for women with ovarian cancer. Nine major recommendations are outlined in this Opinion article. PMID:21941283

  14. [Ovarian activity of Agouti paca (Rodentia: Agoutidae) under captivity].

    Science.gov (United States)

    Montes Pérez, Rubén C; Cabrera Baz, Elsy A

    2006-09-01

    The ovarian activity of Agouti paca was characterized by hormonal profiles and ovarian structures. Samples of blood were taken from eight females (seven adults and one juvenile) at the breeding grounds of the Facultad de Medicina Veterinaria y Zootecnia in Yucatśn, Mexico. Sampling lasted approximately two months and was done every three and six days. Blood was collected from anesthetized animals, and the levels of progesterone (P4) and 17 beta estradiol (E2) were analized by radioimmunoassay technique. Macroscopic and microscopic analyses were carried out in ovaries of dead animals. The estrous cycle lasted 29+/-8.4 days, levels of 1.61+/-0.65 ng/ml for P4 and 39+/-24 pg/ml for E2 were observed for a follicular phase, 6.18+/-3.70 ng/ml and 29+/-16 pg/ml for P4 and E2 respectively in the luteal phase. Statistically significant differences were found between phases for P4 but not for E2. The presence of extragonadal steroids with levels of P4 of 1.9+/-0.77 ng/ml and E2 of 22+/-17 pg/ml were observed, which are not produced by the effects of managing stress. The changes in the levels of P4 during the cycle are indicators of luteal activity, with the intersticial tissue acting probably as active steroids-producing gland. Follicular growth was observed during the entire cycle.

  15. Ovarian metastasis of malignant melanoma: The first pediatric case

    Directory of Open Access Journals (Sweden)

    Yuko Araki

    2014-10-01

    Full Text Available We report a case of an 8-year-old girl with metastasis of malignant melanoma (MM to the ovary. She was initially diagnosed with cutaneous MM on the left buttock for which she underwent wide local excision, left inguinal/pelvic lymph node dissection, and subcutaneous injection of interferon beta. In spite of the treatment, she developed dissemination of MM to the liver, the bone, and the right ovary. All the lesions responded well to systemic chemotherapy (intravenous dacarbazine, except for the right ovarian tumor. She underwent an elective right salpingo-oophorectomy to avoid torsion or rupture of the tumor. However, she developed metastases to the contralateral ovary with peritoneal dissemination in 4 months. She received home palliative care and died at home 14 months after the last surgery. Ovarian metastasis of MM is a rare form of dissemination, and only 15 adult cases have ever been reported. Our patient is the first pediatric case. Since there is no standard of surgical indication for metastatic MM to the ovary, palliative resection can be an option for improving quality of life of a patient with this rare condition.

  16. Ovarian dysgerminoma in two sisters

    Directory of Open Access Journals (Sweden)

    Bander F Aldhafery

    2008-01-01

    Full Text Available Although rare, dysgerminomas are important irrespective of incidence because they affect women of reproductive age (i.e., <45 years. Dysgerminomas make up two thirds of all malignant ovarian neoplasms in women younger than 20 years. All dysgerminomas are considered malignant, but only one third of dysgerminomas behave aggressively. Their exact etiology has not been determined. Few reports are found in the review of the literature on the incidence of dysgerminoma and other germ cell tumors in families. Some of these reports focus on the genetic abnormalities associated with germ cell tumor and the responsible gene. Two cases of dysgerminomas diagnosed in two sisters aged 14 and 19 years old are presented here with their radiological studies.

  17. Huge bilateral ovarian cysts in adulthood as the presenting feature of Van Wyk Grumbach syndrome due to chronic uncontrolled juvenile hypothyroidism

    Directory of Open Access Journals (Sweden)

    K S Shivaprasad

    2013-01-01

    Full Text Available Juvenile primary hypothyroidism causing cystic ovaries and pseudoprecocious puberty (Van-Wyk Grumbach syndrome (VWGS is well documented in literature. There are only a few reports of primary hypothyroidism presenting as ovarian cysts in adults. Here we present a case of huge bilateral ovarian cysts in adulthood as the presenting feature of VWGS due to chronic uncontrolled juvenile hypothyroidism. Large uniloculor right ovarian cyst (119 × 81 × 90 mm and a multicystic left ovary (55 × 45 × 49 mm were detected in a 24 year lady with secondary amenorrhea, galactorrhea, and palpable abdominal mass with history of neonatal jaundice, delayed milestones, short stature, and precocious menarche at age of 7.5 years age. She had elevated levels of cancer antigen (CA-125 which normalized post levothyroxine supplementation. Elevated CA-125 may lead to misdiagnosis of ovarian carcinoma and inadvertent treatment. Bilateral ovarian cysts in adults are a rare presentation of juvenile hypothyroidism. It is necessary to screen for primary hypothyroidism in patients presenting with bilateral ovarian cysts to prevent unnecessary evaluation and treatment.

  18. Pembrolizumab, Bevacizumab, and Cyclophosphamide in Treating Patients With Recurrent Ovarian, Fallopian Tube, or Primary Peritoneal Cancer

    Science.gov (United States)

    2016-07-29

    Fallopian Tube Clear Cell Adenocarcinoma; Fallopian Tube Endometrioid Adenocarcinoma; Fallopian Tube Mucinous Adenocarcinoma; Fallopian Tube Serous Adenocarcinoma; Ovarian Clear Cell Adenocarcinoma; Ovarian Endometrioid Adenocarcinoma; Ovarian Mucinous Adenocarcinoma; Ovarian Serous Adenocarcinoma; Primary Peritoneal Serous Adenocarcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Undifferentiated Fallopian Tube Carcinoma; Undifferentiated Ovarian Carcinoma

  19. Ormeloxifene efficiently inhibits ovarian cancer growth

    Science.gov (United States)

    Maher, Diane M.; Khan, Sheema; Nordquist, Jordan; Ebeling, Mara C.; Bauer, Nichole A.; Kopel, Lucas; Singh, Man Mohan; Halaweish, Fathi; Bell, Maria C.; Jaggi, Meena; Chauhan, Subhash C.

    2014-01-01

    Ovarian cancer continues to be a leading cause of cancer related deaths for women. Anticancer agents effective against chemo-resistant cells are greatly needed for ovarian cancer treatment. Repurposing drugs currently in human use is an attractive strategy for developing novel cancer treatments with expedited translation into clinical trials. Therefore, we examined whether ormeloxifene (ORM), a non-steroidal Selective Estrogen Receptor Modulator (SERM) currently used for contraception, is therapeutically effective at inhibiting ovarian cancer growth. We report that ORM treatment inhibits cell growth and induces apoptosis in ovarian cancer cell lines, including cell lines resistant to cisplatin. Furthermore, ORM treatment decreases Akt phosphorylation, increases p53 phosphorylation, and modulates the expression and localization patterns of p27, cyclin E, cyclin D1, and CDK2. In a pre-clinical xenograft mouse ORM treatment significantly reduces tumorigenesis and metastasis. These results indicate that ORM effectively inhibits the growth of cisplatin resistant ovarian cancer cells. ORM is currently in human use and has an established record of patient safety. Our encouraging in vitro and pre-clinical in vivo findings indicate that ORM is a promising candidate for the treatment of ovarian cancer. PMID:25306892

  20. Unbalanced estrogen metabolism in ovarian cancer.

    Science.gov (United States)

    Zahid, Muhammad; Beseler, Cheryl L; Hall, James B; LeVan, Tricia; Cavalieri, Ercole L; Rogan, Eleanor G

    2014-05-15

    Greater exposure to estrogens is a risk factor for ovarian cancer. To investigate the role of estrogens in ovarian cancer, a spot urine sample and a saliva sample were obtained from 33 women with ovarian cancer and 34 age-matched controls. Thirty-eight estrogen metabolites, conjugates and DNA adducts were analyzed in the urine samples using ultraperformance liquid chromatography/tandem mass spectrometry, and the ratio of adducts to metabolites and conjugates was calculated for each sample. The ratio of depurinating estrogen-DNA adducts to estrogen metabolites and conjugates was significantly higher in cases compared to controls (p < 0.0001), demonstrating high specificity and sensitivity. DNA was purified from the saliva samples and analyzed for genetic polymorphisms in the genes for two estrogen-metabolizing enzymes. Women with two low-activity alleles of catechol-O-methyltransferase plus one or two high-activity alleles of cytochrome P450 1B1 had higher levels of estrogen-DNA adducts and were more likely to have ovarian cancer. These findings indicate that estrogen metabolism is unbalanced in ovarian cancer and suggest that formation of estrogen-DNA adducts plays a critical role in the initiation of ovarian cancer. PMID:24170413

  1. Multi-step radioimmunotherapy of ovarian carcinomatosis

    International Nuclear Information System (INIS)

    Ovarian cancer is the leading cause of mortality among gynecological malignancies. Some 70 - 80% of patients fail conventional therapy, eventually succumbing to ovarian carcinomatosis. We are exploring a multi-step targeting approach as an adjuvant therapy to surgical debulking of the tumour. The prospective intraperitoneal treatment involves administration of a bispecific antibody to target CA-125 on the surface of ovarian cancer cells and biotin; followed by administration of biotinylated, radiolabeled liposomes to effect selective tumour cell killing within the peritoneal cavity. The goal of the study is to provide efficacious control of peritoneal metastatic disease, with improved quality and duration of the life of the patient. Bispecific antibodies to the human ovarian tumour-associated antigen, CA-125, were engineered and their selective targeting of human NIH:OVCAR-3 ovarian cancer cells was demonstrated by confocal laser scanning microscopy. Co-localisation of biotinylated, long-circulating liposomes was demonstrated, using the same technique. Kinetics analysis of internalisation and shedding of the antigen/antibody complex demonstrates an effective residency on the cell surface for at least four hours in vitro. Biodistribution studies in immunodeficient Balb/c mice demonstrate selective tumour association of radiolabeled, targeted liposomes. Tumour growth delay/control studies are imminently planned. Our current results warrant further development of this approach as a potential therapy for human ovarian carcinomatosis

  2. Genomic analysis of epithelial ovarian cancer

    Institute of Scientific and Technical Information of China (English)

    John Farley; Laurent L Ozbun; Michael J Birrer

    2008-01-01

    Ovarian cancer is a major health problem for women in the United States.Despite evidence of considerable heterogeneity,most cases of ovarian cancer are treated in a similar fashion.The molecular basis for the clinicopathologic characteristics of these tumors remains poorly defined.Whole genome expression profiling is a genomic tool,which can identify dysregulated genes and uncover unique sub-classes of tumors.The application of this technology to ovarian cancer has provided a solid molecular basis for differences in histology and grade of ovarian tumors.Differentially expressed genes identified pathways implicated in cell proliferation,invasion,motility,chromosomal instability,and gene silencing and provided new insights into the origin and potential treatment of these cancers.The added knowledge provided by global gene expression profiling should allow for a more rational treatment of ovarian cancers.These techniques are leading to a paradigm shift from empirical treatment to an individually tailored approach.This review summarizes the new genomic data on epithelial ovarian cancers of different histology and grade and the impact it will have on our understanding and treatment of this disease.

  3. Oligodendroglioma arising in a mature cystic ovarian teratoma in a child.

    Science.gov (United States)

    Büyükka Bay, Sema; Corapcioglu, Funda; Kavurt, Sumru; Müezzinoğlu, Bahar; Anik, Yonca; Tugay, Melih

    2010-11-01

    In childhood mature cystic teratomas are the most common type of ovarian germ cell tumors. Tumors of neuroepithelial origin are extremely rare in mature teratomas. To the authors' knowledge, this is the first case report oligodendroglioma arising in a mature cystic ovarian teratoma in children. A 13-year-old girl presented with a history of pelvic pain for 2 months. An ultrasound examination showed a monolateral multicystic, calcific ovarian mass, measuring approximately 6 x 5 cm, arising in the left over and adnexia, suggesting a teratoma. An exploratorative laparotomy and ooferectomy were performed. On histopatological examination, various samples from cystic areas had mature tissues from all 3 germ cell layers, including skin, bone, bronchial structures, and cerebellum. Sections from solid areas showed uniform population of monotonous, rounded cells with indistinct cytoplasm and having perinuclear halo (fried-egg appearance) on a fibrillary, neuropilic background. Microcalcifications as calcospherites were noted in the stroma. Based on the typical morphological features, the cased was diagnosed as mature cystic teratoma with low-grade oligodendroglioma. To the authors' knowledge, there are a few reports in the literature of an oligodendroglioma arising in an ovarian teratoma in adults and this presented patient is the first case in childhood.

  4. Ovarian Grafts 10 Days after Xenotransplantation: Folliculogenesis and Recovery of Viable Oocytes.

    Science.gov (United States)

    Campos-Junior, Paulo Henrique Almeida; Alves, Thalys Jair Melo; Dias, Marco Tulio; Assunçao, Carolina Marinho; Munk, Michele; Mattos, Matheus Silvério; Kraemer, Lucas Rocha; Almeida, Brígida Gomes; Russo, Remo Castro; Barcelos, Lucíola; Camargo, Luiz Sérgio Almeida; Viana, Joao Henrique Moreira

    2016-01-01

    Ovarian xenotransplantation is a promising alternative to preserve fertility of oncologic patients. However, several functional aspects of this procedure remained to be addressed. The aim of this study was evaluate the feasibility of xenotransplantation as a strategy to maintain bovine ovarian grafts and produce oocytes. Adult ovarian cortical pieces were xenotransplanted to the dorsal subcutaneous of female NOD-SCID mice (n = 62). Grafts were recovered ten days after xenotransplantation. Host and graft weights; folliculogenesis progression; blood perfusion, relative gene expression and number of macrophage and neutrophil of xenografts; in vitro developmental competence of graft-derived oocytes were evaluated. Folliculogenesis was supported in the grafts, as indicated by the presence of primordial, primary, secondary, antral, and atretic follicles. The xenografts showed a greater volumetric density of atretic follicles and higher hyperemia and number of host-derived macrophage and neutrophil (Panimals than in control and non-grafted (P<0.01). BAX and PRDX1 genes were up-regulated, while BCL2, FSHR, IGF1R and IGF2R were down-regulated, when compared to the control (P<0.01). Twenty seven oocytes were successfully harvested from grafts, and some of these oocytes were able to give rise to blastocysts after in vitro fertilization. However, cleavage and blastocyst rates of xenograft derived oocytes were lower than in control (P<0.01). Despite showing some functional modifications, the ovarian xenografts were able to support folliculogenesis and produce functional oocytes. PMID:27362486

  5. Unilateral sectioning of the superior ovarian nerve of rats with polycystic ovarian syndrome restores ovulation in the innervated ovary

    Directory of Open Access Journals (Sweden)

    Morales-Ledesma Leticia

    2010-08-01

    Full Text Available Abstract The present study tested the hypothesis that if polycystic ovary syndrome (PCOS results from activating the noradrenergic outflow to the ovary, unilaterally sectioning the superior ovarian nerve (SON will result in ovulation by the denervated ovary, and the restoration of progesterone (P4, testosterone (T and estradiol (E2 normal serum level. A single 2 mg dose of estradiol valerate (EV to adult rats results in the development of a syndrome similar to the human PCOS. Ten-day old rats were injected with EV or vehicle solution (Vh and were submitted to sham surgery, unilateral or bilateral sectioning of the SON at 24-days of age. The animals were sacrificed at 90 to 92 days of age, when they presented vaginal estrus preceded by a pro-estrus smear. In EV-treated animals, unilateral sectioning of the SON restored ovulation by the innervated ovary and unilateral or bilateral sectioning of the SON normalized testosterone and estradiol levels. These results suggest that aside from an increase in ovarian noradrenergic tone in the ovaries, in the pathogenesis of the PCOS participate other neural influences arriving to the ovaries via the SON, regulating spontaneous ovulation. Changes in P4, T and E2 serum levels induced by EV treatment seem to be controlled by neural signals arising from the abdominal wall and other signals arriving to the ovaries through the SON, and presents asymmetry.

  6. Predictors of ovarian response : progress towards individualized treatment in ovulation induction and ovarian stimulation

    NARCIS (Netherlands)

    Fauser, B. C. J. M.; Diedrich, K.; Devroey, P.

    2008-01-01

    Ovarian stimulation is applied in the clinic to restore mono-ovulatory cycles in anovulatory women (ovulation induction) or to induce the development of multiple dominant follicles for assisted reproduction. Ovarian response is the endocrine and follicular reaction of the ovaries to stimulation. Ach

  7. Bilateral ovarian cystic teratomata mimicking bilateral pure ovarian hemangiomata: case report.

    Science.gov (United States)

    Feuerstein, I M; Aronson, B L; McCarthy, E F

    1984-01-01

    This report describes a case of bilateral, benign cystic ovarian teratomata which were composed predominantly of cavernous hemangiomatous elements. The right-sided lesion, in particular, mimicked a pure ovarian hemangioma. The clinical presentation, bilaterality of the lesions, the sizes of the hemangiomata, and the subsequent hemangioma of the leg are all of interest in this very rare lesion. PMID:6511164

  8. Reference values in ovarian response to controlled ovarian stimulation throughout the reproductive period.

    Science.gov (United States)

    La Marca, Antonio; Grisendi, Valentina; Spada, Elena; Argento, Cindy; Milani, Silvano; Plebani, Maddalena; Seracchioli, Renato; Volpe, Annibale

    2014-01-01

    Abstract The age-related decline in ovarian response to gonadotropins has been well known since the beginning of ovarian stimulation in IVF cycles and has been considered secondary to the age-related decline in ovarian reserve. The objective of this study was to establish reference values and to construct nomograms of ovarian response for any specific age to gonadotropins in IVF/ICSI cycles. We analyzed our database containing information on IVF cycles. According to inclusion and exclusion criteria, a total of 703 patients were selected. Among inclusion criteria, there were regular menstrual cycle, treatment with a long GnRH agonist protocol and starting follicle-stimulating hormone (FSH) dose of at least 200 IU per day. To estimate the reference values of ovarian response, the CG-LMS method was used. A linear decline in the parameters of ovarian response with age was observed: the median number of oocytes decreases approximately by one every three years, and the median number of follicles >16 mm by one every eight years. The number of oocytes and growing follicles corresponding to the 5th, 25th, 50th, 75th and 95th centiles has been calculated. This study confirmed the well known negative relationship between ovarian response to FSH and female ageing and permitted the construction of nomograms of ovarian response.

  9. Toxicity and population structure of the Rough-Skinned Newt (Taricha granulosa) outside the range of an arms race with resistant predators.

    Science.gov (United States)

    Hague, Michael T J; Avila, Leleña A; Hanifin, Charles T; Snedden, W Andrew; Stokes, Amber N; Brodie, Edmund D; Brodie, Edmund D

    2016-05-01

    Species interactions, and their fitness consequences, vary across the geographic range of a coevolutionary relationship. This spatial heterogeneity in reciprocal selection is predicted to generate a geographic mosaic of local adaptation, wherein coevolutionary traits are phenotypically variable from one location to the next. Under this framework, allopatric populations should lack variation in coevolutionary traits due to the absence of reciprocal selection. We examine phenotypic variation in tetrodotoxin (TTX) toxicity of the Rough-Skinned Newt (Taricha granulosa) in regions of allopatry with its TTX-resistant predator, the Common Garter Snake (Thamnophis sirtalis). In sympatry, geographic patterns of phenotypic exaggeration in toxicity and toxin-resistance are closely correlated in prey and predator, implying that reciprocal selection drives phenotypic variation in coevolutionary traits. Therefore, in allopatry with TTX-resistant predators, we expect to find uniformly low levels of newt toxicity. We characterized TTX toxicity in northwestern North America, including the Alaskan panhandle where Ta. granulosa occur in allopatry with Th. sirtalis. First, we used microsatellite markers to estimate population genetic structure and determine if any phenotypic variation in toxicity might be explained by historical divergence. We found northern populations of Ta. granulosa generally lacked population structure in a pattern consistent with northern range expansion after the Pleistocene. Next, we chose a cluster of sites in Alaska, which uniformly lacked genetic divergence, to test for phenotypic divergence in toxicity. As predicted, overall levels of newt toxicity were low; however, we also detected unexpected among- and within-population variation in toxicity. Most notably, a small number of individuals contained large doses of TTX that rival means of toxic populations in sympatry with Th. sirtalis. Phenotypic variation in toxicity, despite limited neutral genetic

  10. Possibilities and limits of ovarian reserve testing in ART.

    Science.gov (United States)

    La Marca, Antonio; Argento, Cindy; Sighinolfi, Giovanna; Grisendi, Valentina; Carbone, Marilena; D'Ippolito, Giovanni; Artenisio, Alfredo Carducci; Stabile, Gaspare; Volpe, Annibale

    2012-03-01

    Markers of ovarian reserve are associated with ovarian aging as they decline with chronologic age, and hence may predict stages of reproductive aging including the menopause transition. Assessment of ovarian reserve include measurement of serum follicle stimulating hormone (FSH), anti-M�llerian hormone (AMH), and inhibin-B. Ultrasound determination of antral follicle count (AFC), ovarian vascularity and ovarian volume also can have a role. The clomiphene citrate challenge test (CCCT), exogenous FSH ovarian reserve test (EFORT), and GnRH-agonist stimulation test (GAST) are dynamic methods that have been used in the past to assess ovarian reserve. In infertile women, ovarian reserve markers can be used to predict low and high oocyte yield and treatment failure in women undergoing in vitro fertilization. However the markers may have limitations when an in depth analysis of their accuracy, cost, convenience, and utility is performed. As ovarian reserve markers may permit the identification of both the extremes of ovarian stimulation, a possible role for their measurement may be in the individualization of treatment strategies in order to reduce the clinical risk of ART along with optimized treatment burden. It is fundamental to clarify the cost/benefit of its use in the ovarian reserve testing before initiation of an IVF cycle and whether the ovarian reserve markers-determined strategy of ovarian stimulation for assisted conception may be associated to improved live birth rate.

  11. A correlative microscopical analysis of differentiating ovarian follicles of mammals.

    Science.gov (United States)

    Anderson, E; Wilkinson, R F; Lee, G; Meller, S

    1978-06-01

    The mammalian ovary has been studied by optical microscopy and by scanning and transmission electron microscopy with the purpose of presenting an integrated view of the differentiating mammalian follicle. During follicular development, changes in the granulosa cells are particularly noteworthy and include dramatic modifications in cell shape coincident with antrum formation. The cytoplasmic processes of those granulosa cells immediately surrounding the oocyte, as well as the more peripheral granulosa cells comprising a second and third layer, traverse the zona pellucida, infrequently interdigitate with the microvilli of the egg, and make both desmosomal and gap junction contacts with the oocyte. The zona pellucida is thus distinguished by numerous fenestrations of varying diameters. The membrana limitans (basal lamina) is a bipartite structure composed of (a) a homogenous stratum upon which the peripheral layer of granulosa cells rests, and (b) an outer region of collagen-like fibers. The specific advantages and limitations of the different methodologies utilized to study folliculo-genesis are discussed. PMID:671553

  12. Coffee, tea, and caffeine consumption and risk of epithelial ovarian cancer and borderline ovarian tumors

    DEFF Research Database (Denmark)

    Gosvig, Camilla F; Kjaer, Susanne K; Blaakær, Jan;

    2015-01-01

    BACKGROUND: Epidemiological studies that have investigated the association between coffee, tea and caffeine consumption and ovarian cancer risk have produced conflicting results. Furthermore, only few studies have examined the role of coffee and tea consumption separately for borderline ovarian...... tumors. By use of data from a large Danish population-based case-control study, we examined the risk of ovarian tumors associated with coffee, tea, and caffeine consumption with a particular focus on characterizing risks by tumor behavior and histology. MATERIAL AND METHODS: From 1995 through 1999, we....... RESULTS: Both coffee (OR = 0.90; 95% CI 0.84-0.97 per cup/day) and total caffeine consumption from coffee and tea combined (OR = 0.93; 95% CI 0.88-0.98 per 100 mg/day) decreased the risk of ovarian cancer. These associations were significant only for the serous and "other" subtypes of ovarian cancer...

  13. Economic Valuation Related to Illegal Extraction of Orchid Cattleya granulosa Within the naTural Park Dom Nivaldo Monte from Natal/RN

    Directory of Open Access Journals (Sweden)

    Adriana Margarida Zanbotto Ramalho

    2010-04-01

    Full Text Available The Atlantic Rain Forest has been the subject of biopiracy and predation of ornamental plants like orchids that reach a high market value. The Natural Park Dom Nivaldo Monte is a fragment of the Atlantic Rain Forest, covering 64 hectares in the city of Natal-RN, which has been the target of this illegal market due to extraction plant of Cattleya granulosa, an endemic orchid endangered. This study aimed to do an economical valuation of the environmental damage caused by the illegal extraction of orchid C. granulosa. The methodology of the survey included the following steps: sample survey of the orchid in the study area and calculation of absolute density and frequency; Economic valuation of environmental damage by using the method proposed by the State Department of Natural Resource Protection – São Paulo – Brazil; proposition the public policies in order to control the environmental impacts in the area. The results pointed out an absolute density and frequency were 1.17 individuals/plot and 8.33%, estimated 1493 individuals, during the period analyzed. The environmental services provided by all individuals of C. granulosa society, in the study area represents a monetary value of R$ 9,555,200.00. It was proposed as a municipal public policies for the preservation of species: increased enforcement in the area, environmental education with the surrounding community, the recovery of damages to the offender, creation of ecological boarder and use of plant biotechnology techniques.

  14. Differential responsiveness of luteinized human granulosa cells to gonadotropins and insulin-like growth factor I for induction of aromatase activity

    International Nuclear Information System (INIS)

    The objective of this study was to examine the in vitro responsiveness of cultured luteinized human granulosa cells over time to insulin-like growth factor 1 (IGF-1), human follicle-stimulating hormone (FSH), and human chorionic gonadotropin (hCG) for the induction of aromatase activity. Granulosa cells were retrieved from preovulatory follicles in patients undergoing in vitro fertilization. Cells were cultured for a period of 72 hours or 10 days. The ability of hCG, human FSH, and/or IGF-I to induce aromatase activity was assayed by the stereospecific release of tritium from [1B-3H]androstenedione. Short-term cultures (72 hours) demonstrated a marked rise in aromatase activity in response to human FSH and IGF-I, whereas a smaller response to hCG was observed. In contrast, 10-day cultures demonstrated responsiveness predominantly to hCG rather than human FSH for the induction of aromatase activity with no remarkable effect of IGF-I. Luteinized human granulosa cells undergo a transformation from an initial human FSH and IGF-I responsive state to an hCG responsive state in long-term cultures

  15. Ovarian response during IVF cycle following laparascopic cystectomy of ovarian endometrioma

    Directory of Open Access Journals (Sweden)

    Nasrin Moghadami Tabrizi

    2013-07-01

    Full Text Available Background: Endometrioma of ovary is one of the common diseases during reproductive age and the effect of laparoscopic cystectomy of endometrioma on infertility is still matter of debate. We designed this case control study to evaluate the ovarian response to controlled ovarian hyperstimulation during IVF (In vitro fertilization cycle following laparoscopic unilateral cystectomy of endometrioma. Methods: In a case control study, we enrolled 30 women with history of unilateral laparoscopic cystectomy of ovarian endometrioma in stripping method who underwent IVF cycle in women Hospital, 2009-2012. The numbers of follicles in response to controlled ovarian hyperstimulation during IVF cycle in the ovary with history of  unilateral laparoscopic cystectomy of endometrioma were compared with those from the contralateral ovary. Results: The mean age (±SD of patients was 32.3 (±3.4. The mean (±SD diameter of excised ovarian endometrioma was 42.4 (±10.4 mm. Interval since ovarian surgery to induction ovulation was 2.7 (±2.6 years. Mean number of follicles in the ovary with history of unilateral laparoscopic cystectomy of endometrioma was 2.5 (±1.2 with the range of 1 to 5 and in the control ovary 3.9 (±1.4 with the range of 1 to 6. There was significant difference in the number of follicles in the ovary with laparascopic cystectomy of endometrioma compared with opposite one (P<0.001.Conclusion: Laparoscopic cystectomy for unilateral endometrioma is associated with a reduced ovarian response to controlled ovarian hyperstimulation during IVF cycle. We did not find any statistically significant difference in reduced ovarian response with regard to patients age, body mass index, size and location of the cyst, and time duration since ovarian cystectomy.

  16. Effects of melatonin on the ovarian response to pinealectomy or continuous light in female rats: similarity with polycystic ovary syndrome

    Directory of Open Access Journals (Sweden)

    M.F. Prata Lima

    2004-07-01

    Full Text Available The current study was conducted to investigate the relationship between melatonin and chronic anovulation. Adult (3-4 months old female Wistar rats were submitted to pinealectomy: group I: pinealectomized ovariectomized melatonin-treated (N = 10; group II: pinealectomized ovariectomized placebo-treated (N = 12; group III: pinealectomized light-treated placebo-treated(N = 10 or maintained under continuous light; group IV: maintained under continuous light, ovariectomized melatonin-treated (N = 22; group V: maintained under continuous light, ovariectomized placebo-treated (N = 10; group VI: maintained under continuous light placebo-treated (N = 10. In order to assess ovarian modifications, unilateral ovariectomy was performed during the fourth month in groups I, II, IV, V and the other ovary was removed after 8 months. Ovariectomy was performed in groups III and VI only after eight months. Melatonin (200 µg/100 g body weight dissolved in 0.02 ml absolute ethanol was injected intramuscularly daily during the last 4 months into groups I and IV. The other groups were treated with placebo (NaCl. The ovarian cysts were analyzed and their area, perimeter and maximum diameter, as well as the thickness of the ovarian capsule were measured. Daily colpocytological smears were performed throughout the study. Persistent estrous condition and ovarian cysts were observed in all groups. In pinealectomized rats the ovarian and vaginal alterations disappeared at the end of the study and in rats maintained under continuous light the vaginal and ovarian polycystic aspect was reversed only in those treated with melatonin. We conclude that melatonin may act on the ovarian response reverting chronic anovulation induced by pinealectomy or continuous light.

  17. Extracellular matrix of the developing ovarian follicle.

    Science.gov (United States)

    Irving-Rodgers, Helen F; Rodgers, Raymond J

    2006-09-01

    There are many different types of extracellular matrices in the different follicle compartments. These have different roles in follicle development and atresia, and they change in composition during these processes. This review focuses on basal lamina matrix in particular, and considers follicular fluid, the newly identified focimatrix, and thecal matrices. When follicles commence growing, the follicular basal lamina changes in its composition from containing all six alpha chains of type IV collagen to only alpha1 and alpha2. Perlecan and nidogen-1 and -2 subsequently become components of the follicular basal lamina, and there is an increase in the amount of laminin chains alpha1, beta2, and gamma1, in the bovine at least. Late in follicular development and on atresia some follicles contain laminin alpha2. On atresia the follicular basal lamina is not degraded, as occurs in ovulation, but can be breached by cells from the thecal layer when it is not aligned by granulosa cells. A novel type of basal lamina-like matrix, called focimatrix (abbreviated from focal intraepithelial matrix), develops between the cells of the membrana granulosa as aggregates of basal lamina material. It does not envelop cells and so cannot perform functions of basal lamina as currently understood. It is hypothesized that focimatrix assists or initiates depolarization of the membrana granulosa necessary for the transformation into luteal cells. The largest osmotically active molecules in follicular fluid are hyaluronan and chondroitin sulfate proteoglycans, including versican and inter-alpha trypsin inhibitor. It has been suggested that these might be responsible for the formation of follicular fluid by creating an osmotic gradient across the follicular wall. The formation, development, and then either ovulation or regression of follicles requires considerable tissue remodeling, cellular replication, and specialization. The expectation of researchers is that extracellular matrix will be

  18. Recent alcohol consumption and risk of incident ovarian carcinoma

    DEFF Research Database (Denmark)

    Kelemen, Linda E; Bandera, Elisa V; Terry, Kathryn L;

    2013-01-01

    Studies evaluating the association between alcohol intake and ovarian carcinoma (OC) are inconsistent. Because OC and ovarian borderline tumor histologic types differ genetically, molecularly and clinically, large numbers are needed to estimate risk associations....

  19. The relation between endometriosis and ovarian cancer - a review

    DEFF Research Database (Denmark)

    Heidemann, Lene Nyhøj; Hartwell, Dorthe; Heidemann, Christian Hamilton;

    2014-01-01

    Endometriosis is known to harbor characteristics substantiating that it is a possible precursor of ovarian cancer.......Endometriosis is known to harbor characteristics substantiating that it is a possible precursor of ovarian cancer....

  20. Decrease of free thyroxine levels after controlled ovarian hyperstimulation

    NARCIS (Netherlands)

    A.F. Muller (Alex); A. Verhoeff; M.J. Mantel; F.H. de Jong (Frank); A. Berghout (Arie)

    2000-01-01

    textabstractControlled ovarian hyperstimulation could lead to opposing effects on thyroid function. Therefore, in a prospective study of 65 women undergoing controlled ovarian hyperstimulation, thyroid hormones, T4-binding globulin, TPO antibodies, gonadotropins, estrad