Sample records for luteolysis

  1. Ganirelix for luteolysis in poor responder patients undergoing IVF treatment: a Scandinavian multicenter 'extended pilot study'

    DEFF Research Database (Denmark)

    Nilsson, Lena; Andersen, A.N.; Lindenberg, Svend


    To enhance oocyte yield and pregnancy outcome in poor responder women undergoing IVF treatment, daily low dose GnRH antagonist administration was given during the late luteal phase to induce luteolysis and possibly secure a more synchronous cohort of recruitable follicles. An open extended pilot...

  2. Ganirelix for luteolysis in poor responder patients undergoing IVF treatment: a Scandinavian multicenter 'extended pilot study'

    DEFF Research Database (Denmark)

    Nilsson, Lena; Andersen, A.N.; Lindenberg, Svend


    To enhance oocyte yield and pregnancy outcome in poor responder women undergoing IVF treatment, daily low dose GnRH antagonist administration was given during the late luteal phase to induce luteolysis and possibly secure a more synchronous cohort of recruitable follicles. An open extended pilot...... study in four Scandinavian fertility centers was done including 60 patients. Poor response was defined as when 2000 IU FSH. GnRH antagonist (ganirelix) was given, 0.25 mg s.c. daily, from days 3 to 5...... oocyte retrievals resulting in 5 pregnancies (4 delivered). Despite GnRH antagonist administration in the late luteal phase and menstrual bleeding, FSH was not sufficiently reduced to secure a more synchronic cohort of recruitable follicles. Novel GnRH antagonists more specifically targeting FSH release...

  3. Oxytocin is not involved in luteolysis and early maternal recognition of pregnancy (MRP) in alpacas. (United States)

    Ciccarelli, Michela; Waqas, Muhammad Salman; Pru, James K; Tibary, Ahmed


    Pregnancy maintenance depends on the maternal recognition of pregnancy (MRP), a physiological process by which the lifespan of the corpus luteum is prolonged. This mechanism is not well characterized in camelids. The objectives of the present research were to determine if exogenous oxytocin prolongs the corpus luteum activity in alpacas and to evaluate expression and localization of oxytocin receptors within the endometrium at 9 and 14days post-mating. In the oxytocin studies, plasma progesterone profiles were determined after ovulation in the same alpacas on 2 cycles: one cycle without oxytocin treatment and one cycle with oxytocin treatment. Oxytocin was administered daily by intramuscular injections (IM) at a dose of 20IU (experiment 1, n=6) or 60IU (experiment 2, n=7 from day 3 through day 10 after induction of ovulation with GnRH IM. There was no significant difference in the length of the luteal phase (i.e. corpus luteum lifespan) between the treated and control cycles using either 20 or 60IU of oxytocin. In the final experiment, uteri from open and pregnant alpacas (n=4 per group) at 9 and 14days post-mating were evaluated for expressions of oxytocin receptors by immunohistochemistry. No significant difference (P≤0.05) in the expression of oxytocin receptors was observed between open and pregnant animals in either staining intensity or tissue localization. We conclude that oxytocin is not involved in luteolysis and early MRP in alpacas. Published by Elsevier B.V.

  4. Progesterone levels and days to luteolysis in mares treated with intrauterine fractionated coconut oil. (United States)

    Diel de Amorim, Mariana; Nielsen, Kayla; Cruz, Raissa Karolliny Salgueiro; Card, Claire


    Intrauterine plant oil infusion, including fractionated coconut oil, has been previously found to be a safe, inexpensive, and reversible method of prolonging the luteal phase in mares when administered on Day 10 of the estrous cycle. Our objective was to understand the uteroovarian response to the administration of fractionated coconut oil infusion in the uterus of diestrous mares. We hypothesized that intrauterine coconut oil administration on Day 10 would prolong luteal life span in a dose-dependent fashion and would result in higher serum progesterone levels than untreated mares at the expected time of luteolysis. Light-horse mares (n = 18) were examined using transrectal palpation and ultrasonography to determine if they had a normal interovulatory interval and were then examined daily in estrus until the day of ovulation (Day 0) and then every other day during an estrous cycle. Jugular blood was drawn on Day 11, Day 13, Day 15, and Day 17, centrifuged, and serum stored until assayed for progesterone (P4; Siemens Coat-a-Count Progesterone RIA, Los Angeles, CA, USA). Mares were randomly assigned to treatment and studied over one to two estrous cycles with a rest cycle after each treatment cycle. Groups were: control (n = 5), fractionated coconut oil 1.0 mL (Miglyol 810; Sasol Oil, Witten, Germany) infused in the uterus with an artificial insemination pipette on Day 10 (Group 1; n = 5) and fractionated coconut oil 0.5 mL infused in the uterus with an embryo transfer gun, on Day 10 (Group 2; n = 5). All statistical analyses were performed using analytical software (Stata SE, version 13.1, College Station, TX, USA) at P < 0.05. Data were first evaluated using the Shapiro-Wilk test for normality. Differences between groups in days to luteolysis (DTL) were examined using analysis of variance and Bonferroni, and the effect of day and treatment on P4 levels were examined using the Kruskal-Wallis and Dunn's all pairwise test. There was a significant

  5. Elevated concentrations of 13,14-dihydro-15-keto-prostaglandin F-2 alpha in maternal plasma during prepartum luteolysis and parturition in dogs (Canis familiaris). (United States)

    Concannon, P W; Isaman, L; Frank, D A; Michel, F J; Currie, W B


    Concentrations of progesterone and of 13,14-dihydro-15-keto-prostaglandin F-2 alpha (PGFM) were measured in plasma collected from 6 bitches every 3 h starting 2.8-4.6 days before parturition (birth of first pup) and continuing until 0.4-0.8 days post partum, and in additional samples collected less frequently. Progesterone concentrations at 48, 24, 12 and 3 h pre partum averaged 2.8 +/- 0.3, 2.2 +/- 0.4, 1.0 +/- 0.3 and 0.7 +/- 0.2 ng/ml. At those times PGFM values averaged 380 +/- 80, 800 +/- 220, 1450 +/- 450 and 1930 +/- 580 pg/ml, respectively. Mean concentrations of PGFM increased about 2.5-fold between 48 and 15 h pre partum in association with the onset of luteolysis, and then increased another 2.5 times before parturition as progesterone fell to nadir values. Peak levels of PGFM ranged from 1060 to 7150 pg/ml (2100 +/- 600 pg/ml) and occurred within 1-9 h after the birth of the first pup and before the birth of the last pup. These results suggest that prepartum luteolysis in dogs is initiated by increases in maternal concentrations of PGF, and that progesterone withdrawal causes a further increase in PGF which completes luteolysis and provides a major portion of the uterotonic activity causing expulsion of pups.

  6. Interplacental uterine expression of genes involved in prostaglandin synthesis during canine pregnancy and at induced prepartum luteolysis/abortion (United States)


    Background In the non-pregnant dog, ovarian cyclicity is independent of a uterine luteolysin. This is in contrast to pregnant animals where a prepartum increase of luteolytic PGF2α occurs, apparently originating in the pregnant uterus. Recently, the placenta as a source of prepartum prostaglandins (PGs) was investigated, indicating fetal trophoblast cells as the likely main source. However, the possible contribution of uterine interplacental tissues to the production of these hormones has not yet been thoroughly examined in the dog. Methods Several key factors involved in the production and/or actions of PGs were studied: cyclooxygenase 2 (COX2, PTGS2), PGF2α-synthase (PGFS/AKR1C3), PGE2-synthase (PGES), and the respective receptors FP (PTGFR), EP2 (PTGER2) and EP4 (PGTER4), 15-hydroxyprostaglandin dehydrogenase (HPGD), PG-transporter (PGT, SLCO2A1) and progesterone receptor. Their expression and localization patterns were assessed by Real Time PCR and immunohistology in the interplacental uterine sites from pregnant dogs during the pre-implantation period (days 8–12), post-implantation (days 18–25), mid-gestation (days 35–40) and during antigestagen-induced luteolysis/abortion. Results Whereas only low COX2 expression was observed in uterine samples at all the selected time points, expression of PGFS/AKR1C3 strongly increased post-implantation. A gradual increase in PGES-mRNA expression was noted towards mid-gestation. FP-mRNA expression decreased significantly with the progression of pregnancy until mid-gestation. This was associated with clearly detectable expression of HPGD, which did not change significantly over time. The expression of FP and EP2-mRNA decreased significantly over time while EP4-mRNA expression remained unaffected. The antigestagen-treatment led to a significant increase in expression of COX2, PGES, EP2 and PGT (SLCO2A1) mRNA. COX2 was localized predominantly in the myometrium. The expression of PGFS/AKR1C3, which was unchanged, was

  7. Does the conceptus of the viviparous lizard Barisia imbricata imbricata participates in the regulation of progesterone production and the control of luteolysis? (United States)

    Martínez-Torres, Martín; Salcedo-Álvarez, Martha; Alvarez-Rodríguez, Carmen; Cárdenas-León, Mario; Luis, Juana; Moreno-Fierros, Leticia


    It is generally accepted that progesterone is necessary to maintain gestation; however, the mechanisms that control the production of this steroid remain unknown. The corpus luteum has been assigned a central role in the maintenance of gestation based on its capacity to produce progesterone. A pseudopregnancy model was performed in a viviparous lizard, Barisia imbricata imbricata, to determine whether the absence of embryos would affect the pattern of progesterone production or the corpus luteum histology. Blood samples were obtained prior to ovulation and at 8, 16, and 24 weeks after ovulation (pseudopregnant and pregnant lizards), as well as one day after parturition (pregnant lizards) or 32 weeks after ovulation (pseudopregnant lizards). The corpus luteum was surgically removed one day after blood samples were obtained. Blood aliquots from nongravid females were obtained at similar timepoints. We found a significant reduction in plasma progesterone concentrations at 24 and 32 weeks post-ovulation in pseudopregnant lizards compared with those observed at similar times in intact pregnant lizards, whereas the progesterone levels in non-gestant lizards remained significantly lower than in either pseudopregnant or pregnant lizards. Moreover, we observed that the histological appearance of the corpus luteum from pseudogestational females (obtained 24 and 32 weeks post-ovulation) differed from the corpora lutea from lizards in late gestation and intact parturient lizards. These observations suggest that the conceptus participates in the regulation of progesterone production in late gestation and also in luteolysis control. Copyright © 2014 Elsevier B.V. All rights reserved.


    African Journals Online (AJOL)



    Apr 10, 2013 ... The common feature of the reproduction biotechnologies consist maximization of the genetic ... effect. To induce luteolysis, they used PGF2α-based preparations. ..... rature, humidity, air currents, so on) and technological.

  9. Roles of prostaglandin F2alpha and hydrogen peroxide in the regulation of Copper/Zinc superoxide dismutase in bovine corpus luteum and luteal endothelial cells

    Directory of Open Access Journals (Sweden)

    Vu Hai V


    Full Text Available Abstract Background Prostaglandin F2alpha (PGF induces luteolysis in cow by inducing a rapid reduction in progesterone production (functional luteolysis followed by tissue degeneration (structural luteolysis. However the mechanisms of action of PGF remain unclear. Reactive oxygen species (ROS play important roles in regulating the luteolytic action of PGF. The local concentration of ROS is controlled by superoxide dismutase (SOD, the main enzyme involved in the control of intraluteal ROS. Thus SOD seems to be involved in luteolysis process induced by PGF in cow. Methods To determine the dynamic relationship between PGF and ROS in bovine corpus luteum (CL during luteolysis, we determined the time-dependent change of Copper/Zinc SOD (SOD1 in CL tissues after PGF treatment in vivo. We also investigated whether PGF and hydrogen peroxide (H2O2 modulates SOD1 expression and SOD activity in cultured bovine luteal endothelial cells (LECs in vitro. Results Following administration of a luteolytic dose of PGF analogue (0 h to cows at the mid-luteal stage, the expression of SOD1 mRNA and protein, and total SOD activity in CL tissues increased between 0.5 and 2 h, but fell below the initial (0 h level at 24 h post-treatment. In cultured LECs, the expression of SOD1 mRNA was stimulated by PGF (1–10 microM and H2O2 (10–100 microM at 2 h (P

  10. Effect of n-3 and n-6 fatty acid supplementation on fetal, gestation ...

    African Journals Online (AJOL)



    Jul 18, 2011 ... Essential fatty acids (EFAs) include two series of prostaglandin ... functions such as ovulation, luteolysis and parturition. Actions of PGF2α are ..... cations vary according to the type of polyunsaturated fat and the ratio of n-6: n-3 ...

  11. Effects of the 3β-hydroxysteroid dehydrogenase inhibitor trilostane on luteal progesterone production in the dog

    NARCIS (Netherlands)

    de Gier, J.; Wolthers, C.H.; Galac, S.; Schaefers-Okkens, A.C.; Kooistra, H.S.


    Abstract Interference with the pregnancy-maintaining influence of progesterone is the basis of most methods for termination of unwanted pregnancy in dogs. The currently available methods are based on induction of luteolysis or blocking of the progesterone receptor. Inhibition of progesterone

  12. Effect of estradiol and oxytocin on ovine cervical relaxation

    African Journals Online (AJOL)



    Feb 7, 2012 ... The aim of this study was to examine the effect of estradiol (E2) and oxytocin ... Artificial insemination (AI) is a good way for the use of superior rams in reproduction but the conception rates in ... successful in sheep industry because it is costly, time .... during luteolysis and its abrogation in early pregnancy.

  13. The period of the follicular phase during which the uterus of mares shows estrus-like echotexture influences the subsequent pregnancy rate

    NARCIS (Netherlands)

    Mateu-Sánchez, S; Newcombe, J R; Garcés-Narro, C; Cuervo-Arango, J


    The interval from both spontaneous and prostaglandin (PGF)-induced luteolysis to ovulation is greatly variable in mares. Several reports have shown a positive association between the length of the interval from PGF treatment to ovulation (ITO) and the subsequent pregnancy rate (PR). However, it is

  14. Primary uterine inertia in four labrador bitches. (United States)

    Davidson, Autumn P


    Uterine inertia is a common cause of dystocia in the bitch and is designated as primary (i.e., uterine contractions fail to ever be initiated) or secondary (i.e., uterine contractions cease after a period of time but before labor is completed). The etiology of primary uterine inertia is not well understood. The accurate diagnosis of primary uterine inertia requires the use of tocodynamometry (uterine monitoring). Primary uterine inertia has been postulated to result from a failure of luteolysis resulting in persistently elevated progesterone concentrations. In this study, primary uterine inertia was diagnosed in a series of four bitches in which luteolysis was documented suggesting some other etiopathogenesis for primary uterine inertia.

  15. Luteal and placental function in the bitch: spatio-temporal changes in prolactin receptor (PRLr) expression at dioestrus, pregnancy and normal and induced parturition


    Hoffmann Bernd; Guscetti Franco; Boos Alois; Gram Aykut; Michel Erika; Kowalewski Mariusz P; Aslan Selim; Reichler Iris


    Abstract Background Endocrine mechanisms governing canine reproductive function remain still obscure. Progesterone (P4) of luteal origin is required for maintenance of pregnancy. Corpora lutea (CL) are gonadotrop-independent during the first third of dioestrus; afterwards prolactin (PRL) is the primary luteotropic factor. Interestingly, the increasing PRL levels are accompanied by decreasing P4 concentrations, thus luteal regression/luteolysis occurs in spite of an increased availability of g...

  16. The progesterone receptor antagonist, onapristone has differential effects on the timing and control of the luteolytic mechanism depending on timing of administration in sheep. (United States)

    Mann, G E; Wathes, D C; Robinson, R S


    Cyclic ewes were treated with control vehicle or progesterone receptor antagonist (onapristone; 100mg i.m. twice daily) during either early (day 3-5) or late (day 12-14) luteal phase and plasma samples collected for hormone analysis and to determine endogenous and oxytocin induced PGF2α release. On day 14 and 17, ewes were euthanised and reproductive tracts collected for ovarian morphology and endometrium for oxytoxin and steroid hormone receptor analysis. Early treatment increased LH, but not progesterone or oestradiol, while late treatment elevated all three hormones. Early treatment delayed the up-regulation of endometrial oxytocin receptors and responsiveness to oxytocin challenge, delaying luteolysis. Late treatment advanced development of oxytocin receptors and responsiveness to oxytocin though not timing of luteolysis. Patterns of hormone receptor mRNA were differentially disrupted by treatments. Results provide mechanistic insight into hormonal control of the oestrous cycle and identify the ability of the luteolytic mechanism to dissociate from functional luteolysis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  17. Transcriptome analysis reveals differences in mechanisms regulating cessation of luteal function in pregnant and non-pregnant dogs. (United States)

    Zatta, Sophie; Rehrauer, Hubert; Gram, Aykut; Boos, Alois; Kowalewski, Mariusz Pawel


    In the domestic dog, corpora lutea (CL) are the only source of progesterone (P4), both in pregnant and non-pregnant cycles because there is no placental steroidogenesis. The absence of an endogenous luteolysin in absence of pregnancy results in long-lasting physiological pseudopregnancy, strongly contrasting with the acute luteolysis observed prepartum. The underlying biological mechanisms and the involvement of P4 signalling remain, however, not fully understood. Therefore, here, next-generation sequencing (RNA-Seq) was performed on CL from the late luteal phase and compared with normally luteolyzing CL collected at the prepartum P4 decrease. The contrast "luteal regression over luteolysis" yielded 1595 differentially expressed genes (DEG). The CL in late luteal regression were predominantly associated with functional terms linked to extracellular matrix (p = 5.52e-05). Other terms related to transcriptional activity (p = 2.45e-04), and steroid hormone signalling (p = 2.29e-04), which were more highly represented in late regression than during luteolysis. The prepartum luteolysis was associated with immune inflammatory responses (p = 2.87e-14), including acute-phase reaction (p = 4.10e-06). Immune system-related events were also more highly represented in CL derived from normal luteolysis (p = 7.02e-04), compared with those from dogs in which luteolysis was induced with an antigestagen (1480 DEG in total). Additionally, the withdrawal of P4 at mid-gestation resulted in 92 DEG; over-represented terms enriched in antigestagen-treated dogs were related to the inflammatory response (p = 0.005) or response to IL1 (p = 7.29e-05). Terms related to proliferation, e.g., centrosome organization (p = 0.002) and steroid metabolic processes (p = 0.001), prevailed at mid-gestation. Thereby, our results revealed the nature of luteotropic effects of P4 within canine CL. It appears that, even though they result in diminished steroidogenic output, the effect of

  18. Canine placental prostaglandin E2 synthase: expression, localization, and biological functions in providing substrates for prepartum PGF2alpha synthesis. (United States)

    Gram, Aykut; Fox, Barbara; Büchler, Urs; Boos, Alois; Hoffmann, Bernd; Kowalewski, Mariusz P


    The prepartum output of PGF2alpha in the bitch is associated with increased placental PGE2-synthase (PTGES) mRNA levels. Contrasting with this is a decreased expression of PGF2alpha-synthase (PGFS/AKR1C3) in uteroplacental compartments during prepartum luteolysis, suggesting an involvement of alternative synthetic pathways in PGF2alpha synthesis, for example, conversion of PGE2 to PGF2alpha. However, because the expression and possible functions of the respective PTGES proteins remained unknown, no further conclusion could be drawn. Therefore, a canine-specific PTGES antibody was generated and used to investigate the expression, cellular localization, and biochemical activities of canine uteroplacental PTGES throughout pregnancy and at prepartum luteolysis. Additionally, the biochemical activities of these tissues involved in the conversion of PGE2 to PGF2alpha were investigated. The endometrial PTGES was localized in the uterine surface epithelium at preimplantation and in superficial and deep uterine glands, endothelial cells, and myometrium throughout pregnancy and at parturition. Placental signals were mostly in the trophoblast. The biochemical properties of recombinant PTGES protein were confirmed. Additionally, expression of two PGE2-receptors, PTGER2/EP2 and PTGER4/EP4, revealed their decreasing expression during luteolysis. In contrast, the uteroplacental expression of prostaglandin transporter (PGT) was strongly elevated prior to parturition. These localization patterns resembled that of PTGES. The increased expression of PTGES and PGT at parturition, together with the accompanying decreased levels of PGE2-receptors and the capability of canine uterine and placental homogenates to take part in the conversion of PGE2 to PGF2alpha, as found in this study, suggest that PGE2 could be used locally as a substrate for prepartum PGF2alpha synthesis in the dog. © 2014 by the Society for the Study of Reproduction, Inc.

  19. Elevated utero/placental GR/NR3C1 is not required for the induction of parturition in the dog. (United States)

    Gram, Aykut; Trachsel, Alexandra; Boos, Alois; Kowalewski, Mariusz P


    The endocrine mechanisms that lead to initiation of parturition in dogs are still not fully understood. The prepartum luteolysis is associated with increased prostaglandin (PG) F2α secretion; however, there is no pregnancy- or parturition-related increase in estrogens. Moreover, unlike in other mammalian species, in the dog, increased peripartum levels of cortisol measured sporadically in maternal peripheral blood are not mandatory for normal parturition. Nevertheless, auto/paracrine effects of cortisol at the placental feto-maternal level cannot be excluded. Therefore, the aim of this study was to investigate the expression and localization of glucocorticoid receptor (GR/NR3C1) in canine utero/placental (Ut/Pl) units and uterine interplacental sites at selected time points during pregnancy (pre-implantation, post-implantation and mid-gestation), and at normal and antigestagen-induced parturition. The Ut/Pl expression of GR/NR3C1 did not change significantly from pre-implantation until mid-gestation; however, it was strongly induced during the prepartum luteolysis. Within the interplacental samples, expression of GR/NR3C1-mRNA was greater post-implantation than pre-implantation and did not change afterward, i.e. toward mid-gestation. Compartmentalization studies within the Ut/Pl units, involving placenta, endometrium and myometrium separately, performed at the prepartum luteolysis revealed the highest GR/NR3C1-mRNA levels in placenta compared with endometrium and myometrium. Interestingly, in antigestagen-treated mid-pregnancy dogs, Ut/Pl and interplacental GR/NR3C1-mRNA expression remained unaffected. At the cellular level, placental GR/NR3C1 was clearly detectable in placenta fetalis, i.e. in trophoblast cells. In conclusion, increased expression of GR/NR3C1 during normal parturition, but not following antigestagen-treatment, suggest that it is not required for initiating the signaling cascade of PG synthesis leading to the induction of parturition in the dog.

  20. Luteal and placental function in the bitch: spatio-temporal changes in prolactin receptor (PRLr expression at dioestrus, pregnancy and normal and induced parturition

    Directory of Open Access Journals (Sweden)

    Hoffmann Bernd


    Full Text Available Abstract Background Endocrine mechanisms governing canine reproductive function remain still obscure. Progesterone (P4 of luteal origin is required for maintenance of pregnancy. Corpora lutea (CL are gonadotrop-independent during the first third of dioestrus; afterwards prolactin (PRL is the primary luteotropic factor. Interestingly, the increasing PRL levels are accompanied by decreasing P4 concentrations, thus luteal regression/luteolysis occurs in spite of an increased availability of gonadotropic support. PRL acts through its receptor (PRLr, the expression of which has not yet been thoroughly investigated at the molecular and cellular level in the dog. Methods The expression of PRLr was assessed in CL of non-pregnant dogs during the course of dioestrus (days 5, 15, 25, 35, 45, 65 post ovulation; p.o. as well as in CL, the utero/placental compartments (Ut/Pl and interplacental free polar zones (interplacental sites from pregnant dogs during the pre-implantation, post-implantation and mid-gestation period of pregnancy and during the normal and antigestagen-induced luteolysis. Expression of PRLr was tested by Real Time PCR, immunohistochemistry and in situ hybridization. Results In non-pregnant CL the PRLr expression was significantly upregulated at day 15 p.o. and decreased significantly afterwards, towards the end of dioestrus. CL of pregnancy showed elevated PRLr expression until mid gestation while prepartal downregulation was observed. Interestingly, placental but not interplacental expression of PRLr was strongly time-related; a significant upregulation was observed towards mid-gestation. Within the CL PRLr was localized to the luteal cells; in the Ut/Pl it was localized to the fetal trophoblast and epithelial cells of glandular chambers. Moreover, in mid-pregnant animals treated with an antigestagen, both the luteal and placental, but not the uterine PRLr were significantly downregulated. Conclusions The data presented suggest that the

  1. Luteal and placental function in the bitch: spatio-temporal changes in prolactin receptor (PRLr) expression at dioestrus, pregnancy and normal and induced parturition. (United States)

    Kowalewski, Mariusz P; Michel, Erika; Gram, Aykut; Boos, Alois; Guscetti, Franco; Hoffmann, Bernd; Aslan, Selim; Reichler, Iris


    Endocrine mechanisms governing canine reproductive function remain still obscure. Progesterone (P4) of luteal origin is required for maintenance of pregnancy. Corpora lutea (CL) are gonadotrop-independent during the first third of dioestrus; afterwards prolactin (PRL) is the primary luteotropic factor. Interestingly, the increasing PRL levels are accompanied by decreasing P4 concentrations, thus luteal regression/luteolysis occurs in spite of an increased availability of gonadotropic support. PRL acts through its receptor (PRLr), the expression of which has not yet been thoroughly investigated at the molecular and cellular level in the dog. The expression of PRLr was assessed in CL of non-pregnant dogs during the course of dioestrus (days 5, 15, 25, 35, 45, 65 post ovulation; p.o.) as well as in CL, the utero/placental compartments (Ut/Pl) and interplacental free polar zones (interplacental sites) from pregnant dogs during the pre-implantation, post-implantation and mid-gestation period of pregnancy and during the normal and antigestagen-induced luteolysis. Expression of PRLr was tested by Real Time PCR, immunohistochemistry and in situ hybridization. In non-pregnant CL the PRLr expression was significantly upregulated at day 15 p.o. and decreased significantly afterwards, towards the end of dioestrus. CL of pregnancy showed elevated PRLr expression until mid gestation while prepartal downregulation was observed. Interestingly, placental but not interplacental expression of PRLr was strongly time-related; a significant upregulation was observed towards mid-gestation. Within the CL PRLr was localized to the luteal cells; in the Ut/Pl it was localized to the fetal trophoblast and epithelial cells of glandular chambers. Moreover, in mid-pregnant animals treated with an antigestagen, both the luteal and placental, but not the uterine PRLr were significantly downregulated. The data presented suggest that the luteal provision of P4 in both pregnant and non-pregnant dogs

  2. Effect of pregnancy on endometrial sex steroid receptors and on prostaglandin F2α release after uterine biopsy in heifers

    International Nuclear Information System (INIS)

    Meikle, A.; Garofalo, E.G.; Sahlin, L.; Thatcher, W.W.; Kindahl, H.; Forsberg, M.


    The effect of pregnancy on oestrogen receptor (ER) and progesterone receptor (PR) endometrial expression in heifers was studied. Holstein heifers were not inseminated (controls, n = 8) or inseminated (n = 21). Endometrial biopsies were taken at Day 17 h from the uterine horn ipsilateral to the corpus luteum. Hourly samples were taken on the day of the biopsy in 12 animals (controls = 4 and inseminated = 8) to analyze 15-ketodihydro-PGF 2α (PGFM) and progesterone concentrations. Pregnancy determined by ultrasonography diagnosed 6 pregnant cows. The uterine biopsy increased PGFM concentrations, which remained high for 2 to 4 hours, followed by a transient decrease in progesterone concentrations, but the procedure neither provoked luteolysis nor blocked pregnancy. PGFM concentrations were higher in cyclic than in pregnant cows. No differences in PR mRNA expression were observed among groups, but ER mRNA in pregnant heifers tended to be lower than controls, suggesting that this pathway is implicated in maintenance of pregnancy. (author)

  3. Hormonal levels after ovarian X-irradiation of ewes

    International Nuclear Information System (INIS)

    Driancourt, M.A.; Blanc, M.R.; Mariana, J.C.


    The effects of X-irradiation on ovulation rate, cyclicity and progesterone and FSH levels in Ile-de-France ewes (4 control and 16 irradiated) after they were treated during the breeding season were reported. The doses used (800 and 2400 R) destroyed 50% of all size classes of the follicular population. Ovulation occurred in 87% of the treated ewes (ovulation rate = 1) when they were irradiated 24 h after luteolysis; 78% of the corpora lutea resulting from these ovulations were normal as to length and progesterone production. FSH in treated ewes started to increase 20 h after treatment and remained higher than in the controls until ovulation time. Later, while these levels were similar between groups on the day of ovulation, high ovulatory levels persisted in irradiated ewes. In the next cycles, the length of the follicular phases, ovulation rate and progesterone and FSH levels were similar between groups

  4. The role of nitric oxide in reproduction

    Directory of Open Access Journals (Sweden)

    McCann S.M.


    Full Text Available Nitric oxide (NO plays a crucial role in reproduction at every level in the organism. In the brain, it activates the release of luteinizing hormone-releasing hormone (LHRH. The axons of the LHRH neurons project to the mating centers in the brain stem and by afferent pathways evoke the lordosis reflex in female rats. In males, there is activation of NOergic terminals that release NO in the corpora cavernosa penis to induce erection by generation of cyclic guanosine monophosphate (cGMP. NO also activates the release of LHRH which reaches the pituitary and activates the release of gonadotropins by activating neural NO synthase (nNOS in the pituitary gland. In the gonad, NO plays an important role in inducing ovulation and in causing luteolysis, whereas in the reproductive tract, it relaxes uterine muscle via cGMP and constricts it via prostaglandins (PG.

  5. Radioimmunological progesteron determination in peripheral bovine blood

    International Nuclear Information System (INIS)

    Ender, M.


    A radioimmunological method of determination of the progesterone level in peripheral bovine blood is described which enables a monitoring of the corpus luteum function under varying conditions. There is no dependence of the corpus luteum function on the pituitary gland after endogenous prolactin inhibition with a synthetic prolactin inhibitor in the oestrus cycle and in the end-phase of gravidity. In hysterectomized animals, however, the inhibition of endogenous LH leads to luteolysis. The release of endogenous LH, induced by the administration of an LH release hormone, causes a short increase in progesterone production in the middle phase of the cycle only. The administration of exogenous glucocorticoids during the oestrus cycle did not influence the corpus luteum function. The method described is used in a field test to determine the right time for artificial insemination. There is a significant difference between the progesterone values of impregnated and non-pregnant animals at 16-18 days after insemination. (BSC/AK) [de

  6. Ovarian and endocrine responses in tropical sheep treated with reduced doses of cloprostenol. (United States)

    Contreras-Solis, Ignacio; Vasquez, B; Diaz, T; Letelier, C; Lopez-Sebastian, A; Gonzalez-Bulnes, A


    The present study aimed to assess the efficacy of reduced doses of cloprostenol for synchronizing estrus and ovulation in hair sheep. With the aim to evaluate the luteolytic activity of reduced cloprostenol doses, a first experiment was performed using a relatively large (group H: 126 microg; n=8), medium (group M: 68.25 microg; n=6) and small (group L: 38.5 microg; n=6) cloprostenol dose. Luteolysis was assessed at Days 3 and 6 after injection (Day 0) by progesterone concentrations (P(4)) and transrectal ultrasonography (US). In Experiment 2, sheep were randomly assigned to the same three doses to evaluate a protocol for estrous synchronization using two injections administered 9 days apart. A third trial was performed with ewes treated (9 days apart) with the large dose (H=126 microg; n=12) and with a small dose adjusted for facilitating volume management (LA=43.75 microg; n=12). Presence of estrous cycling was determined in all the ewes by US and P(4) assay, at Days -9, -6, -2, 0 (Day of second cloprostenol injection), 8 and 11. Bleeding and US were done every 4h from 16 h of the beginning of the estrus during the third trial to assess the preovulatory LH surge and timing of ovulation. Additionally, blood samples were drawn at Days 0, 1, 2 and 3 to assess estradiol (Experiments 2 and 3) and P(4) (Experiment 2) concentrations during the ovarian follicular phase. In all experiments, percentage of animals showing luteolysis, preovulatory follicular dynamics and function and percentage of ewes showing behavioral estrus in response to treatment was similar among groups. Timing of estrus for group H was earlier than group L (28.6+/-1.8h compared with 37.1+/-2.4h; Psheep, with the additional advantage of reducing treatment costs.

  7. Colour Doppler Ultrasonography as a Tool to Assess Luteal Function in Santa Inês Ewes. (United States)

    Figueira, L M; Fonseca, J F; Arashiro, Ekn; Souza-Fabjan, Jmg; Ribeiro, Acs; Oba, E; Viana, Jhm; Brandão, F Z


    The aim of this study was to evaluate luteal dynamics in the Santa Inês ewes using colour Doppler (CD) ultrasonography. Oestrus was synchronized in nulliparous females (n = 18), and subsequently, they were only teased (n = 6) or teased and mated (n = 12). Blood samples were collected daily for plasma progesterone (P4 ) concentrations. Ultrasonographic images of corpora lutea (CL) in CD mode were obtained for further analysis in its largest diameter. The CD mode allowed an early sequential monitoring of CL that was visualized by the first time 0.77 ± 0.62 days after ovulation, with luteal area 29.68 ± 13.21 mm(2) . During the luteogenesis, a progressive increase was observed, followed by a plateau of luteal area, vascularization area and plasma concentrations of P4 reaching maximum values in D11 (124.0 ± 38.0 mm(2) , 52.78 ± 24.08 mm(2) and 11.23 ± 4.89 ng/ml, respectively). In the luteolysis, the plasma concentrations of P4 decreased sharply, whereas luteal and vascularization area gradually. The vascularization area was positively correlated with plasma concentrations of P4 during the luteogenesis (r = 0.22) and luteolysis (r = 0.48). The luteal dynamics of Santa Inês ewes showed patterns similar to those observed in other sheep breeds studied. The CD ultrasonography has the potential to be used as a tool to assess luteal function in sheep. © 2015 Blackwell Verlag GmbH.

  8. Vascular provisions for a local utero-ovarian cross-over pathway in new world camelids. (United States)

    Del Campo, M R; Del Campo, C H; Ginther, O J


    The right uterine horn of alpacas causes luteolysis in the right ovary, whereas the left horn causes luteolysis in both ovaries. Female reproductive tracts were studied in 32 adult llamas, 12 adult alpacas, and 21 mid-gestation female fetuses to determine if there is a dichotomy in the vascular anatomy between the 2 sides. Adult tracts were studied by either injection of colored latex into the veins and arteries followed by tissue clearing or by injection of colored fluids during transillumination. Fetal uteri were studied by transillumination. The angioarchitecture of the ovarian vascular pedicle was similar to that reported for ewes. There was no vessel comparable to the middle uterine artery, which is the largest uterine artery in the other farm species. A striking difference from the uterine vascular of other farm species was the presence of a major branch of the right uterine artery that crossed the cranial intercornual area to supply much of the left uterine horn. A corresponding major vein originated from the left horn, crossed the mid-line, and terminated as a branch of the right uterine vein. Thus, the vascular anatomy indicated that much venous blood from the left horn drained to the right side. This was confirmed by injection of colored fluid into a small venous branch at the tip of the left horn. The prominent cross-over vessels were observed in the fetal uteri, and the diameter of the left uterine fetal horn (6.7 +/- 0.6 mm) was greater (P blood from the left horn into an artery supplying the right ovary was not defined in this study. However, the results provide an anatomical basis for functional testing of the cross-over hypothesis and defining the area of venoarterial transfer in camelids.

  9. Characterization of hormonal profiles during the luteal phase in regularly menstruating women. (United States)

    Ecochard, Rene; Bouchard, Thomas; Leiva, Rene; Abdulla, Saman; Dupuis, Olivier; Duterque, Olivia; Garmier Billard, Marie; Boehringer, Hans; Genolini, Christophe


    To characterize the variability of hormonal profiles during the luteal phase in normal cycles. Observational study. Not applicable. Ninety-nine women contributing 266 menstrual cycles. The women collected first morning urine samples that were analyzed for estrone-3-glucuronide, pregnanediol-3-alpha-glucuronide (PDG), FSH, and LH. The women had serum P tests (twice per cycle) and underwent ultrasonography to identify the day of ovulation. The luteal phase was divided into three parts: the early luteal phase with increasing PDG (luteinization), the midluteal phase with PDG ≥10 μg/mg Cr (progestation), and the late luteal phase (luteolysis) when PDG fell below 10 μg/mg Cr. Long luteal phases begin with long luteinization processes. The early luteal phase is marked by low PDG and high LH levels. Long luteinization phases were correlated with low E1G and low PDG levels at day 3. The length of the early luteal phase is highly variable between cycles of the same woman. The duration and hormonal levels during the rest of the luteal phase were less correlated with other characteristics of the cycle. The study showed the presence of a prolonged pituitary activity during the luteinization process, which seems to be modulated by an interaction between P and LH. This supports a luteal phase model with three distinct processes: the first is a modulated luteinization process, whereas the second and the third are relatively less modulated processes of progestation and luteolysis. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  10. Steroid receptor coactivators 1 and 2 mediate fetal-to-maternal signaling that initiates parturition. (United States)

    Gao, Lu; Rabbitt, Elizabeth H; Condon, Jennifer C; Renthal, Nora E; Johnston, John M; Mitsche, Matthew A; Chambon, Pierre; Xu, Jianming; O'Malley, Bert W; Mendelson, Carole R


    The precise mechanisms that lead to parturition are incompletely defined. Surfactant protein-A (SP-A), which is secreted by fetal lungs into amniotic fluid (AF) near term, likely provides a signal for parturition; however, SP-A-deficient mice have only a relatively modest delay (~12 hours) in parturition, suggesting additional factors. Here, we evaluated the contribution of steroid receptor coactivators 1 and 2 (SRC-1 and SRC-2), which upregulate SP-A transcription, to the parturition process. As mice lacking both SRC-1 and SRC-2 die at birth due to respiratory distress, we crossed double-heterozygous males and females. Parturition was severely delayed (~38 hours) in heterozygous dams harboring SRC-1/-2-deficient embryos. These mothers exhibited decreased myometrial NF-κB activation, PGF2α, and expression of contraction-associated genes; impaired luteolysis; and elevated circulating progesterone. These manifestations also occurred in WT females bearing SRC-1/-2 double-deficient embryos, indicating that a fetal-specific defect delayed labor. SP-A, as well as the enzyme lysophosphatidylcholine acyltransferase-1 (LPCAT1), required for synthesis of surfactant dipalmitoylphosphatidylcholine, and the proinflammatory glycerophospholipid platelet-activating factor (PAF) were markedly reduced in SRC-1/-2-deficient fetal lungs near term. Injection of PAF or SP-A into AF at 17.5 days post coitum enhanced uterine NF-κB activation and contractile gene expression, promoted luteolysis, and rescued delayed parturition in SRC-1/-2-deficient embryo-bearing dams. These findings reveal that fetal lungs produce signals to initiate labor when mature and that SRC-1/-2-dependent production of SP-A and PAF is crucial for this process.

  11. Uterine responses to early pre-attachment embryos in the domestic dog and comparisons with other domestic animal species. (United States)

    Graubner, Felix R; Gram, Aykut; Kautz, Ewa; Bauersachs, Stefan; Aslan, Selim; Agaoglu, Ali R; Boos, Alois; Kowalewski, Mariusz P


    In the dog, there is no luteolysis in the absence of pregnancy. Thus, this species lacks any anti-luteolytic endocrine signal as found in other species that modulate uterine function during the critical period of pregnancy establishment. Nevertheless, in the dog an embryo-maternal communication must occur in order to prevent rejection of embryos. Based on this hypothesis, we performed microarray analysis of canine uterine samples collected during pre-attachment phase (days 10-12) and in corresponding non-pregnant controls, in order to elucidate the embryo attachment signal. An additional goal was to identify differences in uterine responses to pre-attachment embryos between dogs and other mammalian species exhibiting different reproductive patterns with regard to luteolysis, implantation, and preparation for placentation. Therefore, the canine microarray data were compared with gene sets from pigs, cattle, horses, and humans. We found 412 genes differentially regulated between the two experimental groups. The functional terms most strongly enriched in response to pre-attachment embryos related to extracellular matrix function and remodeling, and to immune and inflammatory responses. Several candidate genes were validated by semi-quantitative PCR. When compared with other species, best matches were found with human and equine counterparts. Especially for the pig, the majority of overlapping genes showed opposite expression patterns. Interestingly, 1926 genes did not pair with any of the other gene sets. Using a microarray approach, we report the uterine changes in the dog driven by the presence of embryos and compare these results with datasets from other mammalian species, finding common-, contrary-, and exclusively canine-regulated genes. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction.

  12. Endocrine and molecular control of luteal and placental function in dogs: a review. (United States)

    Kowalewski, M P


    In the domestic dog (Canis familiaris), the corpus luteum (CL) is the only source of progesterone (P4) in non-pregnant and pregnant animals. The progesterone secretion profiles are almost identical in both conditions until the last third of the luteal phase when the gradual P4 decline turns into a steep drop in pregnant bitches, indicating the onset of parturition. Consequently, the length of the CL-phase in non-pregnant dogs exceeds the luteal lifespan in pregnant animals. The canine CL-function is regulated by many species-specific regulatory mechanisms, the most intriguing of which is the reported independence of gonadotropic support during the first third of dioestrus. Recently, PGE2 has been proposed as one of the most important luteotropic factors acting locally during this time, but afterwards prolactin (PRL) appears to be the main luteotropic factor. Luteal regression/luteolysis occurs, however, in spite of an increased gonadotropic support. Lately, by demonstrating the expression of PRL-receptor (PRLr), a new insight into possible regulatory mechanisms has indicated that the supply of P4 could be controlled upstream of the steroidogenic machinery at the level of PRLr expression and/or function, subsequently leading to the functional suppression of the steroidogenic machinery. An endogenous source of a luteolytic agent is apparently lacking, implicating the luteal regression in non-pregnant bitches as a passive, degenerative process even if the PGF2α-receptor is constitutively expressed in canine CL. This is in contrast to pregnant dogs in which prepartum luteolysis seems to be an active process of CL destruction by PGF2α of utero/placental origin targeting the luteal PGF2α-receptor. © 2012 Blackwell Verlag GmbH.

  13. Expression and localization of vascular endothelial growth factor A (VEGFA) and its two receptors (VEGFR1/FLT1 and VEGFR2/FLK1/KDR) in the canine corpus luteum and utero-placental compartments during pregnancy and at normal and induced parturition. (United States)

    Gram, Aykut; Hoffmann, Bernd; Boos, Alois; Kowalewski, Mariusz P


    VEGFA is one of the most potent known inducers of angiogenesis. However, the function of angiogenic factors in the canine corpus luteum (CL) of pregnancy and in the pregnant uterus and placenta has not yet been elucidated. Therefore, here we investigated the expression and localization of VEGFA and its receptors (VEGFR1/FLT1 and VEGFR2/FLK1/KDR) in the canine CL and utero-placental compartments (ut-pl) throughout pregnancy until prepartum luteolysis. Antigestagen-mediated effects on expression of VEGF system in ut-pl were elucidated in mid-pregnant dogs. While displaying high individual variation, the luteal VEGFA was elevated during pre-implantation and post-implantation, followed by a decrease during mid-gestation, which was more pronounced at the mRNA level, and showed constant expression afterwards. Within the uterus, it increased following implantation and during mid-gestation in ut-pl compartments, but was downregulated at prepartum luteolysis. Luteal VEGFR1 expression resembled that of VEGFA; VEGFR2 remained unaffected throughout pregnancy. In ut-pl compartments, both receptors increased gradually towards mid-gestation; a prepartum decrease was observed for VEGFR1. Antigestagen-treatment resulted in decreased expression of ut-pl VEGFR1. In the CL, VEGFA stained in luteal cells. Uterine signals of VEGFA and its two receptors were observed in epithelial and vascular compartments, and in myometrium. In placental labyrinth, additionally, trophoblast stained positively. Luteal VEGFR1 was localized to the luteal cells and tunica media of blood vessels, whereas VEGFR2 stained only in capillary endothelial cells. The upregulation of luteal and the ut-pl VEGF system during early gestational stages supports the increased vascularization rate during this time. The diminishing effects of the prepartum endocrine milieu on VEGFA function seem to be more pronounced in the ut-pl units. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Effects of intraluteal implants of prostaglandin E1 or E2 on angiogenic growth factors in luteal tissue of Angus and Brahman cows. (United States)

    Weems, Yoshie S; Ma, Yan; Ford, Stephen P; Nett, Terry M; Vann, Rhonda C; Lewis, Andrew W; Neuendorff, Don A; Welsh, Thomas H; Randel, Ronald D; Weems, Charles W


    Previously, it was reported that intraluteal implants containing prostaglandin E1 or E2 (PGE1 and PGE2) in Angus or Brahman cows prevented luteolysis by preventing loss of mRNA expression for luteal LH receptors and luteal unoccupied and occupied LH receptors. In addition, intraluteal implants containing PGE1 or PGE2 upregulated mRNA expression for FP prostanoid receptors and downregulated mRNA expression for EP2 and EP4 prostanoid receptors. Luteal weight during the estrous cycle of Brahman cows was reported to be lesser than that of Angus cows but not during pregnancy. The objective of this experiment was to determine whether intraluteal implants containing PGE1 or PGE2 alter vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), angiopoietin-1 (ANG-1), and angiopoietin-2 (ANG-2) protein in Brahman or Angus cows. On Day 13 of the estrous cycle, Angus cows received no intraluteal implant and corpora lutea were retrieved, or Angus and Brahman cows received intraluteal silastic implants containing vehicle, PGE1, or PGE2 on Day 13 and corpora lutea were retrieved on Day 19. Corpora lutea slices were analyzed for VEGF, FGF-2, ANG-1, and ANG-2 angiogenic proteins via Western blot. Day-13 Angus cow luteal tissue served as preluteolytic controls. Data for VEGF were not affected (P > 0.05) by day, breed, or treatment. PGE1 or PGE2 increased (P Angus cows compared with Day-13 and Day-19 Angus controls but decreased (P Angus controls. There was no effect (P > 0.05) of PGE1 or PGE2 on ANG-1 in Angus luteal tissue when compared with Day-13 or Day-19 controls, but ANG-1 was decreased (P Angus Vehicle controls when compared with Day-13 Angus controls, which was prevented (P Angus cows. There was no effect (P > 0.05) of PGE1 or PGE2 on ANG-2 in Brahman cows. PGE1 or PGE2 may alter cow luteal FGF-2, ANG-1, or ANG-2 but not VEGF to prevent luteolysis; however, species or breed differences may exist. Published by Elsevier Inc.

  15. Ovarian characteristics in sheep with multiple fecundity genes. (United States)

    McNatty, Kenneth P; Heath, Derek A; Clark, Zaramasina; Reader, Karen; Juengel, Jennifer L; Pitman, Janet L


    Ewes heterozygous for combinations of the Inverdale (FecX I ; I+), Booroola (FecB; B+) and Woodlands (FecX2 W ; W+) mutations have ovulation rates higher than each mutation separately. The aims of the experiments described herein were to examine the ovarian phenotypes in I+B+ and I+B+W+ ewes and to compare these with the appropriate ++ (controls), I+ and BB animals available for this study. The mean ± s.e.m. ovulation rates in the ++ (n = 23), I+ (10), I+B+ (7), I+B+W+ (10) and BB (3) animals were 1.8 ± 0.1, 2.5 ± 0.2, 6.6 ± 1.0, 9.6 ± 0.9 and 9.7 ± 0.9 respectively. The maximum number of granulosa cells per follicle in the ++ and I+ genotypes was accumulated after exceeding 5 mm diameter, whereas in I+B+, I+B+W+ and BB animals, this was achieved when follicles reached >2-3 mm. The number of putative preovulatory follicles, as assessed from those with LH-responsive granulosa cells, 24 h after the induction of luteolysis, was higher (P Reproduction and Fertility.

  16. Possible Roles of CC- and CXC-Chemokines in Regulating Bovine Endometrial Function during Early Pregnancy

    Directory of Open Access Journals (Sweden)

    Ryosuke Sakumoto


    Full Text Available The aim of the present study was to determine the possible roles of chemokines in regulating bovine endometrial function during early pregnancy. The expression of six chemokines, including CCL2, CCL8, CCL11, CCL14, CCL16, and CXCL10, was higher in the endometrium at 15 and 18 days of pregnancy than at the same days in non-pregnant animals. Immunohistochemical staining showed that chemokine receptors (CCR1, CCR2, CCR3, and CXCR3 were expressed in the epithelial cells and glandular epithelial cells of the bovine endometrium as well as in the fetal trophoblast obtained from a cow on day 18 of pregnancy. The addition of interferon-τ (IFNT to an endometrial tissue culture system increased CCL8 and CXCL10 expression in the tissues, but did not affect CCL2, CCL11, and CCL16 expression. CCL14 expression by these tissues was inhibited by IFNT. CCL16, but not other chemokines, clearly stimulated interferon-stimulated gene 15 (ISG15 and myxovirus-resistance gene 1 (MX1 expression in these tissues. Cyclooxygenase 2 (COX2 expression decreased after stimulation with CCL8 and CCL14, and oxytocin receptor (OTR expression was decreased by CCL2, CCL8, CCL14, and CXCL10. Collectively, the expression of chemokine genes is increased in the endometrium during early pregnancy. These genes may contribute to the regulation of endometrial function by inhibiting COX2 and OTR expression, subsequently decreasing prostaglandin production and preventing luteolysis in cows.

  17. The loss of luteal progesterone production in women is associated with a galectin switch via α2,6-sialylation of glycoconjugates. (United States)

    Nio-Kobayashi, Junko; Boswell, Lyndsey; Amano, Maho; Iwanaga, Toshihiko; Duncan, W Colin


    Luteal progesterone is fundamental for reproduction, but the molecular regulation of the corpus luteum (CL) in women remains unclear. Galectin-1 and galectin-3 bind to the sugar chains on cells to control key biological processes including cell function and fate. The expression and localization of LGALS1 and LGALS3 were analyzed by quantitative PCR and histochemical analysis, with special reference to α2,6-sialylation of glycoconjugates in carefully dated human CL collected across the menstrual cycle and after exposure to human chorionic gonadotrophin (hCG) in vivo. The effects of hCG and prostaglandin E2 on the expression of galectins and an α2,6-sialyltransferase 1 (ST6GAL1) in granulosa lutein cells were analyzed in vitro. Galectin-1 was predominantly localized to healthy granulosa lutein cells and galectin-3 was localized to macrophages and regressing granulosa lutein cells. Acute exposure to luteotrophic hormones (hCG and prostaglandin E2) up-regulated LGALS1 expression (P progesterone synthesis. Luteotrophic hormones differentially regulate galectin-1 and galectin-3/α2,6-sialylation in granulosa lutein cells, suggesting a novel galectin switch regulated by luteotrophic stimuli during luteolysis and luteal rescue.

  18. Regulation of intraluteal production of prostaglandins

    Directory of Open Access Journals (Sweden)

    Ottobre Joseph S


    Full Text Available Abstract There is clear evidence for intraluteal production of prostaglandins (PGs in numerous species and under a variety of experimental conditions. In general, secretion of PGs appears to be elevated in the early corpus luteum (CL and during the period of luteolysis. Regulation of intraluteal PG production is regulated by a variety of factors. An autoamplification pathway in which PGF-2alpha stimulates intraluteal production of PGF-2alpha has been identified in a number of species. The mechanisms underlying this autoamplification pathway appear to differ by species with expression of Cyclooxygenase-2 (Cox-2 and activity of phospholipase A2 acting as important physiological control points. In addition, a number of other responses that are induced by PGF-2alpha (decreased luteal progesterone, increased endothelin-1, increased cytokines also have been found to increase intraluteal PGF-2alpha production. Thus, regulation of intraluteal PG production may serve to initiate or amplify physiological signals to the CL and may be important in specific aspects of luteal physiology particularly during luteal regression.

  19. Neural analysis of bovine ovaries ultrasound images in the identification process of the corpus luteum (United States)

    Górna, K.; Jaśkowski, B. M.; Okoń, P.; Czechlowski, M.; Koszela, K.; Zaborowicz, M.; Idziaszek, P.


    The aim of the paper is to shown the neural image analysis as a method useful for identifying the development stage of the domestic bovine corpus luteum on digital USG (UltraSonoGraphy) images. Corpus luteum (CL) is a transient endocrine gland that develops after ovulation from the follicle secretory cells. The aim of CL is the production of progesterone, which regulates many reproductive functions. In the presented studies, identification of the corpus luteum was carried out on the basis of information contained in ultrasound digital images. Development stage of the corpus luteum was considered in two aspects: just before and middle of domination phase and luteolysis and degradation phase. Prior to the classification, the ultrasound images have been processed using a GLCM (Gray Level Co-occurence Matrix). To generate a classification model, a Neural Networks module implemented in the STATISTICA was used. Five representative parameters describing the ultrasound image were used as learner variables. On the output of the artificial neural network was generated information about the development stage of the corpus luteum. Results of this study indicate that neural image analysis combined with GLCM texture analysis may be a useful tool for identifying the bovine corpus luteum in the context of its development phase. Best-generated artificial neural network model was the structure of MLP (Multi Layer Perceptron) 5:5-17-1:1.

  20. Update on Multiple Ovulations in Dairy Cattle. (United States)

    Macmillan, Kira; Kastelic, John P; Colazo, Marcos G


    This review updates the causal mechanisms and risk factors for multiple ovulations (MOV) in cattle. Clearly, MOV can lead to twin pregnancies, which negatively affects the health, production, and reproduction of cows. Therefore, a better understanding of the factors causing MOV may help to reduce twinning. Multiple ovulations occur after two or more follicles deviate and achieve codominance. The MOV rate is influenced by a complex network of hormones. For example, MOV is more common during periods of low progesterone (P4), that is, in anovulatory cattle or when luteolysis coincides with the selection of the future ovulatory follicle. There is also strong evidence for the luteinizing hormone (LH) being the primary factor leading to codominance, as high P4 concentrations suppress the transient LH surges and can reduce the ovulation rate in cattle or even inhibit deviation. Rates of MOV are increased in older and higher-producing dairy cows. Increased milk production and dry matter intake (DMI) increases hormone clearance, including P4; however, the association between milk yield and MOV has not been consistent. Additional risk factors for MOV include ovarian cysts, diet, season, and genetics.

  1. Human ovolution and plasma oxytocin

    International Nuclear Information System (INIS)

    Kumaresan, Perianna; Kumaresan, Malathi; Hossini, Mahmood; Arellano, Carolina; Vasicka, Alois


    Plasma oxytocin (OT) concentrations were measured by radioimmunoassay (RIA) method without extracting plasma in 11 normal menstruating women. Mean plasma OT level began to increase steadily from the 7th day of the menstrual cycle and this level rose up to 20+-5 μU/ml (Mean+-S.E.) on the 10th day of the cycle. OT level declined to 13+-6 μU/ml on the day of the LH peak and continuously declined for another 2 days - then rose. The OT level was higher during the follicular phase than during the luteal phase. In 1 individual OT measured in 2 cycles a year apart showed the highest level of OT coincided with LH and FSH peak and abruptly declined. When there was the highest level of progesterone, the OT level was measurable 1 out of 11 cycles. From this study, we conclude that OT may have a role in human ovulation either synergistically or alone with other ovulatory mechanisms and ovarian estradiol and progesterone control the secretion of OT and also suggests that OT may play some role in the regulation of the luteolysis and the menstrual cycle in women. (author)

  2. Changes in insulin-like growth factor-binding protein-3 messenger ribonucleic acid in endothelial cells of the human corpus luteum: a possible role in luteal development and rescue. (United States)

    Fraser, H M; Lunn, S F; Kim, H; Duncan, W C; Rodger, F E; Illingworth, P J; Erickson, G F


    In the human menstrual cycle, extensive angiogenesis accompanies luteinization; and the process is physiologically important for corpus luteum (CL) function. During luteolysis, the vasculature collapses, and the endothelial cells die. In a conceptual cycle, the CL persists both functionally and structurally beyond the luteoplacental shift. Although luteal rescue is not associated with increased angiogenesis, endothelial survival is extended. Despite the central role of the luteal vasculature in fertility, the mechanisms regulating its development and demise are poorly understood. There is increasing evidence that insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) may be important effectors of luteal function. Here, we have found that IGFBP-3 messenger RNA is expressed in the endothelium of the human CL and that the levels of message change during luteal development and rescue by human CG. The signal was strong during the early luteal phase, but it showed significant reduction during the mid- and late luteal phases. Interestingly, administration of human CG caused a marked increase in the levels of IGFBP-3 messenger RNA in luteal endothelial cells that was comparable to that observed during the early luteal phase. We conclude that endothelial cell IGFBP-3 expression is a physiological property of the CL of menstruation and pregnancy. These observations raise the intriguing possibility that the regulated expression of endothelial IGFBP-3 may play a role in controlling angiogenesis and cell responses in the human CL by autocrine/paracrine mechanisms.

  3. Effects of epidermal growth factor, interleukin 1 and nitric oxide on prostaglandin production by guinea-pig uterus. (United States)

    Keeble, J E; Poyser, N L


    Initial experiments in the present study investigated the effects of epidermal growth factor (EGF), interleukin 1beta (IL-1beta) and sodium nitroprusside (a nitric oxide donor) on the output of prostaglandins from guinea-pig uterus on day 7 of the oestrous cycle. Superfusion of day 7 guinea-pig uterus in vitro with either EGF or sodium nitroprusside increased the output of PGF(2alpha) and 6-keto-PGF(1alpha), but not of PGE(2). IL-1beta had no effect on the output of these three prostaglandins. EGF still increased the output of PGF(2alpha), but did not increase the output of 6-keto-PGF(1alpha) in a calcium-depleted superfusate. Subsequent experiments investigated the effect of sodium nitroprusside on contractile activity of day 7 guinea-pig uterus. Basal spontaneous activity of both the intact uterus and isolated myometrium superfused in vitro was low. Sodium nitroprusside increased the contractile activity of these tissues two- to fourfold. EGF did not affect the contractile activity of the uterus, indicating that sodium nitroprusside-induced contractions are not due to increased prostaglandin production. Overall, the findings indicate that EGF and nitric oxide may act as mediators in the mechanism by which oestradiol acting on a progesterone-primed uterus stimulates the increase in PGF(2alpha) production by the guinea-pig uterus necessary for luteolysis. Nitric oxide may increase the spontaneous activity of the uterus when this activity is low.

  4. Luteinizing hormone-releasing hormone (LHRH) and its analogs for contraception in women: a review. (United States)

    Thau, R B


    In animals, LHRH agonists have multiple sites of action including the pituitary, the gonads, and the reproductive tract. In humans, the major antifertility action of this class of peptides is believed to be mediated via the pituitary. Studies in women have indicated that potent LHRH agonists can block ovulation when administered once daily. In the volunteers who have used these agents no serious side effects were observed, although some women experienced irregular bleeding or amenorrhea. It is anticipated that formal clinical trials could be conducted in the near future to determine the efficacy of continuous LHRH agonist administration. Early attempts to use an LHRH agonist to produce luteal insufficiency, luteolysis, or interruption of pregnancy have either been unsuccessful or the results are still too preliminary to ascertain whether these approaches warrant further trials. LHRH antagonists are believed to act by inhibiting the action of LHRH on the pituitary. Although some of these peptides are known to be active in women, very large doses have been required. Recently several investigators have produced LHRH antagonists with increased potency. In the near future, it should be possible to determine whether these peptides should be considered as potential contraceptives in men or in women.

  5. Endocrinology of pregnancy in the dog: a review. (United States)

    Verstegen-Onclin, K; Verstegen, J


    Pregnancy regulation in the dog is not yet fully elucidated. Since plasma progesterone concentrations are similar in pregnant versus non-pregnant animals, it is a poor reflection on CL function and progesterone metabolism. Increased progesterone secretion by the CL in pregnant animals follows implantation and relaxin secretion by the feto-placental units. Progesterone is absolutely required to maintain pregnancy and no placental sources of progesterone have been identified. Pregnancy can be artificially maintained by progesterone administration. Prolactin secretion appears to be increased in response to the increase in relaxin production and occurs independent of estrogen production by the CL. The respective roles of LH, FSH and prolactin are still unclear, with considerable conflicting evidence among studies. However, it appears that prolactin is absolutely required, whereas LH is either permissive or facilitates CL function during pregnancy. Pre-implantation events are still poorly defined in the bitch, and no embryonic factors have been isolated or purified, preventing early pregnancy diagnosis. Parturition occurs following luteolysis, which results from the release of prostaglandin F(2alpha), which begins 36h prepartum in a process similar to that observed in other species. The role of estrogens at the time of parturition remains undefined.

  6. The corpus luteum of the dog: source and target of steroid hormones? (United States)

    Papa, P C; Hoffmann, B


    Aim of this paper is to review our present understanding on the endocrine control of luteal function in the bitch and to add some new data generated in our laboratories in support of the hypothesis of a paracrine/autocrine role of corpus luteum (CL) derived steroid hormones. Luteal lifespan in non-pregnant dogs often exceeds that of pregnant dogs, where luteal regression terminates in a rapid luteolysis, immediately prior to parturition. In non-pregnant dogs, luteal regression occurs independently of a uterine luteolysin and in spite of increased gonadotropic support during the last third of dioestrus. The CL is the only source of progesterone (P(4)) maintaining pregnancy, and they have the capacity to synthesize oestrogens as substantiated by expression of the CYP19 (aromatase) gene observed in this study. Our data demonstrated that lutein and non-lutein cells of the canine CL express in a rather constant manner the progesterone receptor (PR) and the oestrogen receptor, classifying them as targets for an autocrine/paracrine activity of CL-derived steroids. Therefore, a functional role of P(4) within a positive loop feedback system, including StAR and 3β-hydroxysteroid dehydrogenase, has been postulated. © 2011 Blackwell Verlag GmbH.

  7. Prostaglandin F2alpha- and FAS-activating antibody-induced regression of the corpus luteum involves caspase-8 and is defective in caspase-3 deficient mice

    Directory of Open Access Journals (Sweden)

    Flavell Richard A


    that the receptor for PGF2α has not been shown to be directly coupled to caspase-8 recruitment and activation. We hypothesize that PGF2α initiates luteolysis in vivo, at least in part, by increasing the bioactivity or bioavailability of cytokines, such as FasL and that multiple endocrine factors work in concert to activate caspase-3-driven apoptosis during luteolysis.

  8. Features of natural and gonadotropin-releasing hormone antagonist-induced corpus luteum regression and effects of in vivo human chorionic gonadotropin. (United States)

    Del Canto, Felipe; Sierralta, Walter; Kohen, Paulina; Muñoz, Alex; Strauss, Jerome F; Devoto, Luigi


    The natural process of luteolysis and luteal regression is induced by withdrawal of gonadotropin support. The objectives of this study were: 1) to compare the functional changes and apoptotic features of natural human luteal regression and induced luteal regression; 2) to define the ultrastructural characteristics of the corpus luteum at the time of natural luteal regression and induced luteal regression; and 3) to examine the effect of human chorionic gonadotropin (hCG) on the steroidogenic response and apoptotic markers within the regressing corpus luteum. Twenty-three women with normal menstrual cycles undergoing tubal ligation donated corpus luteum at specific stages in the luteal phase. Some women received a GnRH antagonist prior to collection of corpus luteum, others received an injection of hCG with or without prior treatment with a GnRH antagonist. Main outcome measures were plasma hormone levels and analysis of excised luteal tissue for markers of apoptosis, histology, and ultrastructure. The progesterone and estradiol levels, corpus luteum DNA, and protein contents in induced luteal regression resembled those of natural luteal regression. hCG treatment raised progesterone and estradiol in both natural luteal regression and induced luteal regression. The increase in apoptosis detected in induced luteal regression by cytochrome c in the cytosol, activated caspase-3, and nuclear DNA fragmentation, was similar to that observed in natural luteal regression. The antiapoptotic protein Bcl-2 was significantly lower during natural luteal regression. The proapoptotic proteins Bax and Bak were at a constant level. Apoptotic and nonapoptotic death of luteal cells was observed in natural luteal regression and induced luteal regression at the ultrastructural level. hCG prevented apoptotic cell death, but not autophagy. The low number of apoptotic cells disclosed and the frequent autophagocytic suggest that multiple mechanisms are involved in cell death at luteal

  9. Oviductal morphology in relation to hormonal levels in the snapping turtle, Chelydra serpentina. (United States)

    Alkindi, A Y A; Mahmoud, I Y; Woller, M J; Plude, J L


    Microscopic and in situ visual observations were used to relate circulating hormone levels to morphological changes in the oviduct of the snapping turtle Chelydra serpentina throughout the ovarian cycle. Increase in levels of progesterone (P), estradiol (E2) and testosterone (T) levels coincide with an increase in number and growth of endometrial glands, luminal epithelial cells and secretory droplets throughout the oviduct. Testosterone and estradiol levels rose significantly (P < 0.05) after the May-June period and remained high throughout the rest of the summer. Progesterone levels remained stable throughout the summer, with a brief decline in July due to luteolysis. Hormonal values declined significantly (P < 0.001) at the end of the ovarian cycle in the fall. In situ visual observation of fresh oviducts at different stages of gravidity in recently ovulated turtles revealed that proteinaceous like components from the endometrial glands were released into the lumen to form fibers. The morphological features of the oviduct remained active throughout the summer months even though the snapping turtle is a monoclutch species which deposits all the eggs in late-May to mid-June. The high steroid levels correlate with and may be responsible for the secretory activity present throughout the summer and their decline correlates with change to low secretory activity in the fall. Calcium deposition accompanied by morphological changes in luminal cells are suggestive of secretory activity. In the egg-bearing turtles, uterine Ca2+ concentrations measured by flame atomic absorption spectrophotometry revealed significantly higher Ca2+ concentrations (P < 0.001) in eggs with soft shell than eggs without shell. There was a significant increase in calcium granules and proteinaceous fibers in luminal surface of the uterus during the period of eggshelling. This supports the fact that in the snapping turtle like in other reptiles, eggshelling process occurs in the uterus.

  10. Expression and regulation of prostaglandin transporters, ATP-binding cassette, subfamily C, member 1 and 9, and solute carrier organic anion transporter family, member 2A1 and 5A1 in the uterine endometrium during the estrous cycle and pregnancy in pigs

    Directory of Open Access Journals (Sweden)

    Hwanhee Jang


    Full Text Available Objective Prostaglandins (PGs function in various reproductive processes, including luteolysis, maternal pregnancy recognition, conceptus development, and parturition. Our earlier study has shown that PG transporters ATP-binding cassette, subfamily C, member 4 (ABCC4 and solute carrier organic anion transporter family, member 2A1 (SLCO2A1 are expressed in the uterine endometrium in pigs. Since several other PG transporters such as ABCC1, ABCC9, SLCO4C1, and SLCO5A1 are known to be present in the uterine endometrium, this study investigated the expression of these PG transporters in the porcine uterine endometrium and placenta. Methods Uterine endometrial tissues were obtained from gilts on day (D 12 and D15 of the estrous cycle and days 12, 15, 30, 60, 90, and 114 of pregnancy. Results ABCC1, ABCC9, SLCO4C1, and SLCO5A1 mRNAs were expressed in the uterine endometrium, and levels of expression changed during the estrous cycle and pregnancy. Expression of ABCC1 and ABCC9 mRNAs was localized mainly to luminal and glandular epithelial cells in the uterine endometrium, and chorionic epithelial cells during pregnancy. Conceptuses during early pregnancy and chorioallantoic tissues from mid to late pregnancy also expressed these PG transporters. Estradiol-17β increased the expression of ABCC1 and SLCO5A1, but not ABCC9 and SLCO4C1 mRNAs and increasing doses of interleukin-1β induced the expression of ABCC9, SLCO4C1, and SLCO5A1 mRNAs in endometrial explant tissues. Conclusion These data showed that several PG transporters such as ABCC1, ABCC9, SLCO4C1, and SLCO5A1 were expressed at the maternal-conceptus interface, suggesting that these PG transporters may play an important role in the establishment and maintenance of pregnancy by regulating PG transport in the uterine endometrium and placenta in pigs.

  11. Prohibitin (PHB) acts as a potent survival factor against ceramide induced apoptosis in rat granulosa cells. (United States)

    Chowdhury, Indrajit; Branch, Alicia; Olatinwo, Moshood; Thomas, Kelwyn; Matthews, Roland; Thompson, Winston E


    Ceramide is a key factor in inducing germ cell apoptosis by translocating from cumulus cells into the adjacent oocyte and lipid rafts through gap junctions. Therefore studies designed to elucidate the mechanistic pathways in ceramide induced granulosa cell (GC) apoptosis and follicular atresia may potentially lead to the development of novel lipid-based therapeutic strategies that will prevent infertility and premature menopause associated with chemo and/or radiation therapy in female cancer patients. Our previous studies have shown that Prohibitin (PHB) is intimately involved in GCs differentiation, atresia, and luteolysis. In the present study, we have examined the functional effects of loss-/gain-of-function of PHB using adenoviral technology in delaying apoptosis induced by the physiological ligand ceramide in rat GCs. Under these experimental conditions, exogenous ceramide C-8 (50 μM) augmented the expression of mitochondrial PHB and subsequently cause the physical destruction of GC by the release of mitochondrial cytochrome c and activation of caspase-3. In further studies, silencing of PHB expression by adenoviral small interfering RNA (shRNA) sensitized GCs to ceramide C8-induce apoptosis. In contrast, adenovirus (Ad) directed overexpression of PHB in GCs resulted in increased PHB content in mitochondria and delayed the onset of ceramide induced apoptosis in the infected GCs. Taken together, these results provide novel evidences that a critical level of PHB expression within the mitochondria plays a key intra-molecular role in GC fate by mediating the inhibition of apoptosis and may therefore, contribute significantly to ceramide induced follicular atresia. Copyright © 2011 Elsevier Inc. All rights reserved.

  12. Comparative study of oestrous cycles and ovulation characteristics of cattle kept at different altitudes in Peru

    International Nuclear Information System (INIS)

    Cardenas, H.; Vivanco, W.; Alvarado, E.; Padilla, A.; Flores, A.


    Progesterone (P 4 ) profiles were used to characterize certain aspects of the oestrous cycle in dairy Holstein (H) heifers bred under a typical intensive management system in the central coast area of Peru (12 deg. 05' S, 76 deg. 57' W) and in Brown Swiss (BS) and Simmental (SIM) dual purpose heifers reared under extensive management conditions in the central highlands (14 deg. 07' S, 70 deg. 43' W, 4250 m elevation). In the coastal experiment a group of eight H heifers were evaluated during their normal oestrous cycles, and a similar group after synchronization with norgestomet and oestradiol valerate. Serum concentrations of P 4 were measured throughout the oestrous cycles by RIA in daily samples obtained from the jugular vein. The occurrence of ovulation at 30 h after the onset of standing oestrus was determined by laparoscopy or by rectal palpation. Oestrus detection was performed by visual observation of anatomical changes and homosexual behaviour. In the trial carried out in the highlands, eight naturally cycling BS and seven SIM, as well as eight PGF 2α synchronized BS and four SIM, were studied. Parameters similar to those mentioned for the coastal experiment were evaluated in this trial. The evaluations of the PGF 2α synchronized heifers were performed from the commencement of treatment to the end of the first oestrous cycle. The profiles of serum P 4 during natural oestrous cycles of H heifers on the coast and BS and SIM in the highlands were similar to those already defined for cattle in other environments. The PGF 2α treated BS and SIM heifers showed more rapid luteolysis than control heifers; as a consequence, the overall P 4 profiles in synchronized and natural oestruses were different. However, ovulations occurred about 30 h after the onset of standing oestrus in both naturally cycling and synchronized heifers in both environments. (author). 37 refs, 7 figs, 3 tabs

  13. Biology and endocrinology of ovulation, pregnancy and parturition in the dog. (United States)

    Concannon, P W; McCann, J P; Temple, M


    There is considerable variation among bitches in commonly encountered intervals between cycles (5-12 months), durations of anoestrus (1-8 months), durations of follicular phase pro-oestrus (3-21 days) and periovulatory oestrous behavior (3-21 days), intervals from preovulatory LH surge to oestrus onset (-2 to 5 days), and intervals from fertile mating to parturition (57-68 days). The extent of variation within bitches ranges from slight to great. However, there appears to be very little variation in the intervals from LH surge to ovulation (2 days), to post-ovulatory oocyte maturation (approximately 4 days), to implantation (approximately 18 days), to selected developmental stages of pregnancy, or to parturition (64-66 days). There are no tests diagnostic of early pregnancy. The onset times of persistent pregnancy-specific changes have been estimated, including radio-opaque fetal details (Day 46), elevated blood prolactin values (Day 35), elevated blood relaxin values (Day 25), echogenic heart beats (Day 24) and embryonic vesicles (Day 19), and potentially palpable uterine enlargements (Day 21). As in humans, there is an anaemia of pregnancy involving a 30% reduction in haematocrit and an increased incidence of insulin resistance during the second half of gestation. Ovarian progesterone is required throughout pregnancy. LH and prolactin are luteotrophic in the pregnant bitch as well as during the 2-month luteal phase of the non-pregnant bitch. Parturition follows a luteolysis which occurs during an increase in prostaglandin F-2 alpha that begins 36 h pre partum. Factors regulating the duration of anoestrus are not known but termination of anoestrus is associated with increased pulsatile secretion of LH.

  14. Expression and functional implications of peroxisome proliferator-activated receptor gamma (PPARγ) in canine reproductive tissues during normal pregnancy and parturition and at antiprogestin induced abortion. (United States)

    Kowalewski, Mariusz Pawel; Meyer, Andrea; Hoffmann, Bernd; Aslan, Selim; Boos, Alois


    PPARγ is a nuclear hormone receptor of the PPAR family of transcription factors closely related to the steroid hormone receptors serving multiple roles in regulating reproductive function. Endogenous factors from the arachidonic acid metabolites group serve as ligands for PPARs. PPARγ modifies the steroidogenic capacity of reproductive tissues and has been defined as a key mediator of biological actions of progesterone receptor in granulosa cells; it modulates biochemical and morphological placental trophoblast differentiation during implantation and placentation. However, no such information is available for the dog. Hence, the expression and possible functions of PPARγ were assessed in corpora lutea (CL) and utero/placental (Ut/Pl) compartment collected from bitches (n = 3 to 5) on days 8 to 12 (pre-implantation), 18 to 25 (post-implantation), 35 to 40 (mid-gestation) of pregnancy and at prepartal luteolysis. Additionally, 10 mid-pregnant bitches were treated with the antiprogestin Aglepristone [10mg/Kg bw (2x/24h)]; ovariohysterectomy was 24h and 72 h after the 2nd treatment. Of the two PPARγ isoforms, PPARγ1 was the only isoform clearly detectable in all canine CL and utero/placental samples. The luteal PPARγ was upregulated throughout pregnancy, a prepartal downregulation was observed. Placental expression of PPARγ was elevated after implantation and at mid-gestation, followed by a prepartal downregulation. All changes were more pronounced at the protein-level suggesting that the PPARγ expression may be regulated at the post-transcriptional level. Within the CL PPARγ was localized to the luteal cells. Placental expression was targeted solely to the fetal trophoblast cells; a regulatory role of PPARγ in canine placental development possibly through influencing the invasion of fetal trophoblast cells is suggested. Treatment with Aglepristone led to downregulation of PPARγ in either compartment, implying the functional interrelationship with

  15. Uterine and placental expression of canine oxytocin receptor during pregnancy and normal and induced parturition. (United States)

    Gram, A; Boos, A; Kowalewski, M P


    Oxytocin (OT) plays an important role as an inducer of uterine contractility, acting together with its receptor (OTR) to increase synthesis of prostaglandins. Although OT is commonly used in the treatment for dystocia and uterine inertia in the bitch, little attention has been paid to the role of OT in mechanisms regulating parturition in the dog, so that knowledge about the expression of OTR in the canine uterus and placenta is sparse. Consequently, the expression and cellular localization of OTR were investigated in canine utero/placental compartments and interplacental sites throughout pregnancy and at normal and antigestagen-induced parturition, by real-time PCR, immunohistochemistry, western blot and in situ hybridization. The utero/placental and interplacental expression of OTR was constant from pre-implantation until mid-gestation, with a significant increase observed at prepartum luteolysis. In antigestagen-treated mid-pregnant dogs, OTR was upregulated in both interplacental and utero/placental samples. Besides clear myometrial signals, cellular localization of OTR was evident in the endometrial surface epithelial, stromal and vascular endothelial cells. Weaker signals were observed in superficial and deep uterine glandular epithelial cells. Placental OTR was localized in maternal decidual cells and capillary pericytes. Finally, OTR was colocalized with the progesterone receptor (PGR) in maternal decidual cells, coinciding with previously reported increased availability of prostaglandins in the foetal part of the placenta during normal and induced parturition. These findings suggest involvement of OTR in the signalling cascade leading to the prepartum release of prostaglandins from the pregnant canine uterus. © 2014 Blackwell Verlag GmbH.

  16. Hormonal changes in spontaneous and aglépristone-induced parturition in dogs. (United States)

    Baan, M; Taverne, M A M; de Gier, J; Kooistra, H S; Kindahl, H; Dieleman, S J; Okkens, A C


    To increase our understanding of the endocrine changes associated with parturition in dogs, plasma concentrations of progesterone (P4), 15-ketodihydroprostaglandin F(2alpha) (PGFM), estradiol-17-beta (E2beta), cortisol, ACTH, prolactin (PRL), LH, and FSH were measured in six spontaneously whelping bitches and in six bitches in which parturition was induced with the progesterone-receptor blocker aglépristone on day 58 of pregnancy. Expulsion of pups in the induced group took place in the presence of P4 concentrations that were still elevated. PGFM concentrations increased before parturition in both groups, but levels were lower in the induced bitches. PGFM levels reached a maximum in both groups during parturition and quickly decreased in the spontaneously whelping group after parturition, but remained elevated in the induced group. In both groups, cortisol concentrations reached similar maximum levels during the last 30 h before the onset of expulsion. During the 3 days postpartum, cortisol concentrations were higher in the induced group. The highly variable ACTH concentrations did not differ significantly throughout the study within or between groups. In both groups, E2beta concentrations decreased and PRL concentrations increased between the late gestational period and the 30-h period before parturition. Concentrations of both LH (spontaneously whelping group) and FSH (both groups) decreased between late gestation and the postpartum period. The results of this study illustrate the hormonal changes around parturition in the bitch, and reveal that aglépristone-induced parturition is associated with still incomplete luteolysis, an altered PGFM profile, and elevated postpartum cortisol concentrations as compared with spontaneously whelping dogs.

  17. Relationship of oestrus synchronization method, circulating hormones, luteinizing hormone and prostaglandin F-2 alpha receptors and luteal progesterone concentration to premature luteal regression in superovulated sheep. (United States)

    Schiewe, M C; Fitz, T A; Brown, J L; Stuart, L D; Wildt, D E


    Ewes were treated with exogenous follicle-stimulating hormone (FSH) and oestrus was synchronized using either a dual prostaglandin F-2 alpha (PGF-2 alpha) injection regimen or pessaries impregnated with medroxy progesterone acetate (MAP). Natural cycling ewes served as controls. After oestrus or AI (Day 0), corpora lutea (CL) were enucleated surgically from the left and right ovaries on Days 3 and 6, respectively. The incidence of premature luteolysis was related (P less than 0.05) to PGF-2 alpha treatment and occurred in 7 of 8 ewes compared with 0 of 4 controls and 1 of 8 MAP-exposed females. Sheep with regressing CL had lower circulating and intraluteal progesterone concentrations and fewer total and small dissociated luteal cells on Day 3 than gonadotrophin-treated counterparts with normal CL. Progesterone concentration in the serum and luteal tissue was higher (P less than 0.05) in gonadotrophin-treated ewes with normal CL than in the controls; but luteinizing hormone (LH) receptors/cell were not different on Days 3 and 6. There were no apparent differences in the temporal patterns of circulating oestradiol-17 beta, FSH and LH. High progesterone in gonadotrophin-treated ewes with normal CL coincided with an increase in total luteal mass and numbers of cells, which were primarily reflected in more small luteal cells than in control ewes. Gonadotrophin-treated ewes with regressing CL on Day 3 tended (P less than 0.10) to have fewer small luteal cells and fewer (P less than 0.05) low-affinity PGF-2 alpha binding sites than sheep with normal CL. By Day 6, luteal integrity and cell viability was absent in ewes with prematurely regressed CL. These data demonstrate that (i) the incidence of premature luteal regression is highly correlated with the use of PGF-2 alpha; (ii) this abnormal luteal tissue is functionally competent for 2-3 days after ovulation, but deteriorates rapidly thereafter and (iii) luteal-dysfunctioning ewes experience a reduction in numbers of

  18. Effect of flunixin meglumine and carprofen on pregnancy rates in dairy cattle. (United States)

    von Krueger, X; Heuwieser, W


    Embryonic losses contribute considerably to low pregnancy rates. Between d 8 and 17 after breeding, the conceptus secretes interferon-τ as a mechanism for maternal recognition of pregnancy and maintenance of the corpus luteum. Nonsteroidal antiinflammatory drugs inhibit the synthesis of prostaglandin F(2α) by suppressing the enzyme cyclooxygenase. Flunixin meglumine (FM) has been demonstrated to delay luteolysis and to support embryonic survival. The objective of this study was to evaluate the effect of FM and carprofen on conception rates in dairy heifers and cows, respectively. In experiment 1, the effect of FM on pregnancy rates and progesterone concentrations in dairy heifers was tested. A total of 391 heifers were randomly assigned to 1 of 2 groups. Heifers in the treatment group (n=197) received 2.2 mg of FM i.m./kg of body weight twice on d 14/15 and 15/16 after insemination, whereas heifers in the control group (n=194) remained untreated. Blood samples from 388 heifers were taken on d 14/15 and 21/22 after artificial insemination and analyzed for progesterone. Pregnancy rates were 58.2 and 54.8% for the control and treatment groups, respectively. Mean progesterone concentrations were not affected by treatment and number of artificial insemination service (first or second artificial insemination service), but were affected by time and time × pregnancy status. In experiment 2, the objective was to verify the effects of carprofen, a longer acting nonsteroidal antiinflammatory drug and to evaluate its effect on conception rate to first service in dairy cows. A total of 380 cows were randomly assigned to 1 of 2 treatment groups. Cows in the treatment group (n=194) received 1.4 mg of carprofen s.c./kg of body weight on d 15 after insemination, whereas cows in the control group (n=186) remained untreated. Pregnancy was diagnosed between d 40 and 47 after insemination. Conception rates to first service were 35.5 and 33.0% in the control and treatment groups

  19. Response of lactating dairy cows with or without purulent vaginal discharge to gonadotropin-releasing hormone and prostaglandin F2α. (United States)

    Voelz, B E; Rocha, L; Scortegagna, F; Stevenson, J S; Mendonça, L G D


    Purulent vaginal discharge (PVD) is a common uterine disease in dairy cattle that has negative effects on reproductive performance. Reproductive management programs that synchronize ovulation use gonadotropin-releasing hormone (GnRH) to induce ovulation and prostaglandin F2α (PGF2α) to induce luteolysis. The objectives of this study were to evaluate ovarian response to treatment with GnRH and the odds of bearing a corpus luteum or being inseminated in dairy cows with or without PVD. Another objective was to determine the hazard of insemination after administration of PGF2α in dairy cows with or without PVD. Primiparous (n = 291) and multiparous (n = 402) cows were evaluated for PVD using a Metricheck device at 46 ± 3 and 35 ± 3 days in milk (DIM) (study day 0), respectively. On study day 14, primiparous (n = 107) and multiparous (n = 197) cows were treated with GnRH and subsequent ovulation was recorded. Primiparous (n = 178) and multiparous (n = 368) cows not inseminated by study day 21 were administered PGF2α and response to PGF2α treatment was determined by detection of estrus. Furthermore, cows were categorized by the presence of a CL or being inseminated by study days 14, 21, and 35. Overall prevalence of PVD was 28.5% and 13.4% for primiparous and multiparous cows, respectively. Projected 305-d milk yield was less (P PVD+ multiparous cows compared with PVD- multiparous cows, however, no (P = 0.26) difference was detected between primiparous PVD+ and PVD- cows. Ovulatory response to GnRH treatment was 51.8% and 47.8% for primiparous and multiparous cows, respectively. Primiparous PVD- cows tended (P = 0.06) to be less likely to ovulate to GnRH than primiparous PVD+ cows, whereas multiparous PVD+ cows were less (P = 0.04) likely to ovulate to GnRH than PVD- multiparous cows. The odds of bearing a corpus luteum or being inseminated by study days 14, 21, or 35 was not associated with PVD in primiparous cows. In contrast, the odds of bearing a corpus luteum

  20. The effect of metritis on luteal function in dairy cows (United States)


    Background Disturbed uterine involution impairs ovarian function in the first weeks after calving. This study analyzed the long-term effect of metritis on luteal function of 47 lactating Holstein-Friesian cows during the first four postpartum estrous cycles. Cows with abnormal uterine enlargement and malodorous lochia were classified as having metritis (group M, n = 18), and all others were considered healthy (group H, n = 29). Luteal size was measured once between days 9 and 13 of the first (group H, n = 11; group M, n = 12), second (group H, n = 23; group M, n = 18) and fourth (group H, n = 11; group M, n = 7) postpartum luteal phases. Serum progesterone concentration was measured at the same time. Sixteen cows (group H, n = 9; group M, n = 7) underwent transvaginal luteal biopsy for gene expression analysis of steroidogenic regulatory proteins during the second and fourth cycles. Cows with persistence of the corpus luteum (CL) underwent determination of luteal size, luteal biopsy and serum progesterone measurement once between days 29 and 33, followed by prostaglandin treatment to induce luteolysis. The same procedures were repeated once between days 9 and 13 of the induced cycle. Results The cows in group M had smaller first-cycle CLs than the cows in group H (p = 0.04), but progesterone concentrations did not differ between groups. Luteal size, progesterone concentration and gene expression did not differ between the two groups during the second and fourth cycles. Compared with healthy cows (10%), there was a trend (p = 0.07) toward a higher prevalence of persistent CLs in cows with metritis (33%). Persistent CLs were limited to the first cycle. Persistent CLs and the induced cyclic CLs did not differ with regard to the variables investigated. Conclusions An effect of metritis on luteal activity was apparent in the first postpartum estrous cycle. However, after the first postpartum cycle, no differences occurred

  1. Endocrinologic control of normal canine ovarian function. (United States)

    Concannon, P W


    regression after day 20 to 30 involves periodic cell death, diminution in cell size, low levels of apoptosis and minimal or modest involvement of endogenous prostaglandin F (PGF) production. The canine corpus luteum (CL) is dependent on both LH and prolactin as stimulating luteotrophins by day 15, and as required luteotrophins by days 20-25, if not earlier. Thereafter, both luteotrophins likely have cellular mechanisms of action similar to those reported for other species. Progesterone secretion during pregnancy is greatly enhanced by characteristic, and probably relaxin-stimulated, increases in prolactin concentration starting at or after day 25, and persisting to term. Near term, foetoplacental maturation results in the placental release of large, luteolytic amounts of PGF for 1-2 days pre-partum. Pre-partum luteolysis, like that induced by exogenous prostaglandin, likely involves a cascade enhanced by the removal of progesterone inhibition of PGF release and some degree of intra-luteal PGF synthesis. That a likely twofold or greater increase in progesterone production by the CL of pregnancy does not result in significantly higher serum progesterone than in non-pregnant metoestrus relates to several biological changes, including a large increase in plasma volume of distribution, increased metabolism of progesterone by increased uterine, placental and mammary masses and increased liver clearance and excretion of progesterone and progesterone metabolite. Anoestrus length and ovarian cycle intervals, variable within and among bitches, are likely affected by neuroendocrine components of an endogenous circannual cycle, albeit only photo-entrained in the Basenji breed. This may be modified by the prior luteal phase, exposure to oestrus female pheromones and as yet unknown mechanisms that likely operate via inhibitory opioidergic and/or stimulatory dopaminergic hypothalamic pathways affecting late anoestrus increases in LH.

  2. Circulating progesterone concentrations in nonlactating Holstein cows during reuse of intravaginal progesterone implants sanitized by autoclave or chemical disinfection. (United States)

    Melo, L F; Monteiro, P L J; Oliveira, L H; Guardieiro, M M; Drum, J N; Wiltbank, M C; Sartori, R


    The aim of this study was to compare plasma progesterone (P4) concentrations in nonlactating, multiparous Holstein cows (n = 24) treated with 2 types of intravaginal implants containing either 1.0 or 1.9 g of P4 either at the first use or during reuse of the implants after sanitizing the implant by autoclave or chemical disinfection. In a completely randomized design with a 2 × 3 factorial arrangement and 2 replicates, every cow underwent 2 of 6 treatments. Two sources of P4 [controlled internal drug release (1.9 g of P4) from Zoetis (São Paulo, Brazil), and Sincrogest (1.0 g of P4) from Ourofino (Cravinhos, Brazil)] and 3 types of processing, new (N), reused after autoclave (RA), and reused after chemical disinfection (RC), were used. After inducing luteolysis to avoid endogenous circulating P4, the cows were randomized in 1 of 6 treatments (1.9 g of N, 1.9 g of RA, 1.9 g of RC, 1.0 g of N, 1.0 g of RA, and 1.0 g RC). Cows were treated with the implants for 8 d and during this period blood samples were collected at 0, 2, 12, 24, 48, 72, 96, 120, 144, 168, and 192 h. Statistical analyses were performed using Proc-Mixed and the mean ± standard error of the mean P4 concentrations were calculated using the Proc-Means procedures of SAS 9.4 (SAS Institute Inc., Cary, NC). No interaction between treatments was observed. Comparing types of implant, average P4 concentrations during treatments were greater for 1.9 g than 1.0 g (1.46 vs. 1.14 ± 0.04 ng/mL). When types of processing were compared, average P4 concentrations did not differ between autoclaved and new inserts (1.46 vs. 1.37 ± 0.05 ng/mL; respectively), but both were greater than chemically disinfected implants (1.09 ± 0.04 ng/mL). Within 1.9-g P4 inserts, P4 concentrations from autoclaved implants were greater than new, which were greater than chemically disinfected (1.67 ± 0.06 vs. 1.49 ± 0.07 vs. 1.21 ± 0.05 ng/mL; respectively). For 1.0-g P4 implants, P4 concentrations from autoclaved did not differ

  3. Mechanisms underlying reduced fertility in anovular dairy cows. (United States)

    Santos, J E P; Bisinotto, R S; Ribeiro, E S


    Resumption of ovulation after parturition is a coordinated process that involves recoupling of the GH/insulin-like growth factor 1 axis in the liver, increase in follicular development and steroidogenesis, and removal of negative feedback from estradiol in the hypothalamus. Infectious diseases and metabolic disorders associated with extensive negative energy balance during early lactation disrupt this pathway and delay first ovulation postpartum. Extended periods of anovulation postpartum exert long-lasting effects on fertility in dairy cows including the lack of spontaneous estrus, reduced pregnancy per artificial insemination (P/AI), and increased risk of pregnancy loss. Concentrations of progesterone in anovular cows subjected to synchronized programs for AI are insufficient to optimize follicular maturation, oocyte competence, and subsequent fertility to AI. Ovulation of first wave follicles, which develop under low concentrations of progesterone, reduces embryo quality in the first week after fertilization and P/AI in dairy cows. Although the specific mechanisms by which anovulation and low concentrations of progesterone impair oocyte quality have not been defined, studies with persistent follicles support the involvement of premature resumption of meiosis and degradation of maternal RNA. Suboptimal concentrations of progesterone before ovulation also increase the synthesis of PGF2α in response to oxytocin during the subsequent estrous cycle, which explains the greater incidence of short luteal phases after the first AI postpartum in anovular cows compared with estrous cyclic herd mates. It is suggested that increased spontaneous luteolysis early in the estrous cycle is one of the mechanisms that contributes to early embryonic losses in anovular cows. Anovulation also leads to major shifts in gene expression in elongated conceptuses during preimplantation stages of pregnancy. Transcripts involved with control of energy metabolism and DNA repair were

  4. Efeito do tempo da aplicação de prostaglandina na resposta folicular em ovelhas durante o ciclo estral Effect of time of prostaglandin administration on follicular response in ewes during oestrous cycle

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    Luis Fernando Uribe-Velásquez


    ovarian response, using transrectal ultrasonography, to two injections of Prostaglandin F2α (PGF2α given at different intervals. Fourteen Bergamasca ewes were injected with an i.m. dose of PGF2α during the breeding season. Ewes were randomly alloted in two groups (n = 7 which received PGF2α 7 d (PG7 or 9 d (PG9 after ovulation (when the dominant follicle of wave 2 was expected to be in the growth and plateau phase, respectively. Ovaries were examined daily with transrectal ultrasonography Aloka 500 with 7.5 MHz linear array transducer. Ultrasonography started 1 day prior to the second PG injection and ended 10 d after ovulation for both groups. Jugular vein blood samples were collected daily for progesterone assay. Plasma P4 concentration was lower in PG7 than in PG9, immediately before PGF2α treatment (4.10 ± 0.17 vs 4.91 ± 0.29 ng/mL, respectively. Mean maximum diameter size attained by the dominant follicle of wave 2 was larger in the group treated in PG7 when compared with PG9 (5.5 ± 0.19 vs 4.29 ± 0.26 mm. There was effect of day for total follicles. Number of small follicles (2-2.5 mm was greater (4.57 ± 0.78 vs 8.42 ± 1.36 at day 6, for PG7 and PG9, respectively, whereas no changes were observed in medium follicles (3-3.5 mm between groups treated. The proportion of large follicles (4 mm increased after luteolysis. Values were lower for ewes treated on PG7, whereas values mantained stable over time for ewes treated on PG9. Ewes with rapid and complete luteal regression, ovulation occur from the dominant follicle of wave 2 in females treated on days 7 and 9.