Absence Of Ovaries Research Articles

Monitoring and controlling follicular activity in camelids

This paper reviews that state of our knowledge concerning follicular wave dynamics, monitoring and manipulation. All camelids have overlapping follicular waves in absence of ovulation which is induced by a seminal plasma factor (βNGF). The interval between follicular waves varies. The size of the ovulatory follicle varies between 11 and 25 mm in camels and between in 6 and 13 mm in South American Camelids. The interval between induction of ovulation and next ovulatory follicle is 15 ± 1 day for all camelids. Follicular activity is best monitored by transrectal ultrasonography. Progesterone therapy for 7–15 days seems to suppress follicular dominance but does not completely inhibit follicular recruitment. Combination of estradiol and progesterone seems to provide better control of follicular activity. Both methods have provided variable results in the synchronization of follicular waves. Combination of induction of ovulation with GnRH and luteolysis at predetermined times shows some promise in synchronization of follicular dominance. These synchronization protocols require further investigation in order to provide practical approaches for fixed-time breeding. Ovarian superstimulation with FSH and eCG alone or in combination is somewhat successful. The best results are obtained when treatment is initiated at the emergence of a new follicular wave after induction of ovulation or following treatment with progesterone for 7–14 days. However, response remains extremely variable particularly in terms of ovulation rate and number of recovered embryos. Sources of this variability need to be studied including the effects of season, nutrition, doses and frequency of administration of gonadotropin.

Does serum anti-Müllerian hormone levels always discriminate presence of the ovaries in adult bitches? Comparison of two ELISA kits.

Anti-Müllerian hormone (AMH) is produced in the ovary, and thus, it is an excellent marker of follicle pool in females. Current interest is the clinical use of this parameter as a biomarker to assess presence or absence of an intact ovary and to diagnose ovarian remnant syndrome (ORS) following incomplete ovariohysterectomy (OHE) in bitches. The aim of this study was to evaluate serum AMH concentrations in bitches (n=34) before and after OHE using two different commercial ELISA kits, one of which is based on detecting human AMH and the other is based on detecting human AMH and the other specified for canine AMH. Furthermore, serum AMH levels were also measured in six ORS cases to compare the diagnostic utility of the two different ELISA kits. Serum AMH concentrations measured using the human and canine kit prior to and after OHE were 0.32±0.24, 0.006±0.22ng/ml (p<.001) and 12.08±22.81, 9.55±15.42ng/ml (p=.868), respectively. Thus, the canine-based kit was not able to reveal the significant drop in serum AMH levels. In conclusion, the human-based ELISA kits successfully detected the drop in serum AMH concentrations. Reliable results can only be achieved from well-designed ELISA kits, and AMH levels might be a useful diagnostic tool for the evaluation of presence or absence of ovaries as well as for the detection of ORS cases in bitches.

Ovariectomy increases the age-induced hyperphosphorylation of Tau at hippocampal CA1.

One of the main hallmarks of Alzheimer's disease includes the neurofibrillary tangles formation produced by hyperphosphorylation of the Tau protein, whose expression is putatively regulated by the ovarian hormones estradiol and progesterone. Hippocampus is a brain region that participates in many functions related to learning and memory; in addition, it is abundant in both estradiol and progesterone receptors. In this study, we explore the expression of Tau hyperphosphorylation at hippocampus and the performance of rats in an autoshaping learning task at 5, 10 and 15months after the ovaries removal. In these animals, ovariectomy was performed at 3months of age. These data were compared with those derived from intact rats at 8, 13 and 18months old. A clear decrease in the number of conditioned responses of both intact and ovariectomized rats in the autoshaping learning task was observed. The interaction of both factors confirms that, in this test, learning varies depending on aging and the presence or absence of ovaries. A progressive increase in hippocampal Tau phosphorylation at Ser-396 was observed in either intact or ovariectomized rats. Interestingly, an interaction between the analyzed factors shows that such hyperphosphorylation was potentiated by the absence of ovaries. These results emphasize the importance of aging and the lack of ovarian hormones for an associative learning test and for the expression of one of the most important hallmarks of Alzheimer's disease.

Germline Defects Caused by Smed-boule RNA-Interference Reveal That Egg Capsule Deposition Occurs Independently of Fertilization, Ovulation, Mating, or the Presence of Gametes in Planarian Flatworms.

Few animals are known to lay eggs in the absence of ovulation or copulation, as it is presumably energetically wasteful and subjected to negative selection. Characterization of Smed-boule, a member of the DAZ family of germline RNA-binding proteins, revealed that egg capsule (or capsule) production and deposition occurs independently of the presence of gametes in the planarian flatworm Schmidtea mediterranea. Reduction of Smed-boule expression by RNA-interference (RNAi) causes ablation of spermatogonial stem cells and the inability of ovarian germline stem cells to undergo oogenesis. Although animals subjected to Smed-boule RNAi lose their gametes and become sterile, they continue to lay egg capsules. Production of sterile capsules is even observed in virgin Smed-boule(RNAi) and control planarians maintained in complete isolation, demonstrating that egg production in S. mediterranea occurs independently of ovulation, fertilization, or mating. Evidence suggests that this is a conserved feature amongst Platyhelminthes, and therefore relevant to the pathology and dissemination of parasitic flatworms. These findings demonstrate that Smed-boule functions at different stages during male and female germline stem cell development, and also demonstrate that egg capsule production by planarian flatworms occurs independently of signals produced by mating or ova.

Early menopause: A hazard to a woman's health.

Early menopause or premature ovarian insufficiency (POI) is a common cause of infertility in women and affects about one per cent of young women. This disorder has significant psychological sequelae and major health implications. Its relevance has increased in recent years due to the fact that age of motherhood is being delayed in developed countries, with the risk of having either primary ovarian insufficiency or less possibilities of pregnancy. The main characteristics are absence of ovulation, amenorrhoea and high levels of serum gonadothropins (hypergonadotropic hypogonadism). Although the aetiology remains uncertain in most cases, several rare specific causes have been elucidated. Potential causes for POI are iatrogenic (ovarian surgery, radiotherapy or chemotherapy), environmental factors, viral infections, metabolic and autoinmune diseases, and genetic alterations. Because of the association with other autoimmune diseases, close follow up is recommended in patients with POI. The traditional indicators to evaluate ovarian ageing are age, serum hormonal levels, anti-Mullerian hormone, antral follicle count, and ultrasonography of ovaries. Hormone replacement therapy remains the mainstay of treatment, and the best chance of achieving a pregnancy is through oocyte donation. This article aims to present an overview of potential causes, clinical manifestations, and treatment options of POI.

Patients' auto report of regularity of their menstrual cycles. Medical history is very reliable to predict ovulation. A cross-sectional study.

ObjectiveInfertility of ovulatory cause can account for a quarter of infertility etiologies and one of the questions in the patients' clinical history is about their self-perception of the regularity of their menstrual cycles. The aim of this study was to assess whether the information on menstrual regularity is consistent with the assessment of the presence or absence of ovulation.MethodsCross-sectional study. The inclusion criteria were: patients with infertility for at least one year, complete examination and ovulation monitoring, aged between 18 and 38 years completed. The patients were divided into two paired groups: those who reported regular menstrual cycles and those who reported irregular cycles. In the ultrasonographic monitoring of ovulation we separated those who ovulated from those who did not ovulate, and applied the Fischer's test.ResultsAmong the 199 patients who reported having regular menstrual cycles, 113 had proven ovulation upon ultrasound monitoring and 86 patients did not ovulate. Among the 29 patients who reported irregular cycles, 24 did not ovulated at the cycle monitoring. The Fisher's exact test was applied and the p-value found was significant.ConclusionThe story of the patient in the clinical interview about the presence of regular or irregular menstruation correlates with the presence or absence of ovulation, it should be taken into consideration in the reasoning regarding the infertility etiology. This report would be important to guide the patient's ovulatory regularity diagnosis.

Four Cases with Congenital Unilateral Absence of Ovary and Fallopian Tube: Review of the Literature

Four Cases with Congenital Unilateral Absence of Ovary and Fallopian Tube: Review of the Literature

Non-mosaic monosomy 59,X in cattle: A case report

A 3-year-old Longhorn heifer was referred to the Veterinary Medical Teaching Hospital of Texas A&M University for inability to get pregnant. Physical examination revealed a small-sized female for age and breed with a normal vulva, vaginal length, and external cervical os. Further assessment by per rectum palpation and trans-rectal ultrasonography revealed a small uterine cervix and cord-like uterine horns with no identifiable ovaries. Additional evaluation including laparoscopy, hormonal evaluation, and genetic analysis allowed ruling out conditions commonly associated with a phenotypic female with infantile or underdeveloped reproductive organs such as freemartin, XY gonadal dysgenesis, testicular feminization, and bilateral ovarian agenesis. Laparoscopy confirmed the presence of a small cervix with small uterine horns and absence of ovaries. Testosterone, progesterone, and 17-β estradiol concentrations were 200.0pg/mL, 1.48ng/mL, and undetectable, respectively. Genetic evaluation determined that the karyotype was 59,X non-mosaic. Evaluation of phenotypically female cattle with infertility and infantile genital organs and absence of ovaries should include cytogenetic analysis to test for possible X monosomy. The 59,X condition should be considered in the differential diagnoses together with freemartin, dysgenesis XY, testicular feminization, and bilateral ovarian agenesis.

Concentrations of anti-Müllerian hormone in the domestic cat. Relation with spay or neuter status and serum estradiol

Female cats with unknown history can be diagnosed as spayed or intact with a GnRH-stimulation test or an LH test independent of the stage in the estrous cycle. However, although most females are correctly diagnosed with the LH test, the sensitivity and specificity are not 100%. The GnRH-stimulation test, although reliable, requires an injection of buserelin 2 hours before the blood sample is collected. Granulosa cells are the only cell type that produces anti-Müllerian hormone (AMH) in females, whereas Sertoli cells produce AMH in males. Anti-Müllerian hormone has been linked to spay status in dogs and cats and to ovarian and testicular pathology and fertility in different species. Our aim was to evaluate serum AMH concentrations in spayed female cats and in intact female cats of known age and reproductive stage (inactive ovaries or luteal phase). In addition, our aim was to compare serum AMH concentrations in intact and neutered male cats. We analyzed serum AMH concentrations in 15 spayed and 16 intact females and in 15 intact and 12 neutered male cats. Serum AMH was below the lowest standard point (<0.14 ng/mL) in all spayed females and neutered males, ranged between 1.3 and 19.0 ng/mL in the intact females and between 4.8 and 81.3 ng/mL in intact males. Thus, the AMH test had 100% sensitivity and specificity to diagnose the presence or absence of ovaries and testes in this study. In addition, in contrast to serum estradiol, serum AMH was not affected by buserelin stimulation (P = 0.459). Serum AMH was not correlated with serum estradiol before (rs = −0.188, P = 0.519) or after (rs = 0.335, P = 0.242) buserelin stimulation in the intact females. Four 6-month-old intact cats (two females and two males) had the highest AMH concentrations which in the females might represent a prepubertal peak previously described in other species and in males is likely due to high concentrations before puberty. In conclusion, we found that the AMH Gen II ELISA is reliable for diagnosing spay and neuter status of cats and that the domestic cat might be an interesting model for studies on AMH dynamics.

Drilling ovarien par fertiloscopie : faisabilité, résultats et valeurs prédictives

ObjectivesThe aims of this study were to assess the effectiveness of the ovarian drilling, compare the techniques by fertiloscopy or by laparoscopy, and search for prognostic factors of success. Patients and methodsThis retrospective study focused on 154 ovarian drilling carried out between June 1998 and December 2010 where the drilling has been proposed after failure of the clomifene and before stimulation by FSH among PCOS patients. ResultsThe post-drilling ovulation rate is 62%. The spontaneous on-going pregnancy rate is 31% and the total pregnancy rate scalable including secondary stimulation is 58%. No significant difference was found between laparoscopy and the fertiloscopy. The peroperative complications in fertiloscopy were more frequent but without consequences and 20% of the fertiloscopy had to be converted to laparoscopy, half of them for complications and half of them for technical difficulties. The only found preoperative predictors of success are an euthyroidy that increases the chances of pregnancy in general (including the side stimulation) and a lower FSH levels. However, it appears that the chances of pregnancy in FSH stimulation are dramatically decreased if the drilling did not induce ovulation versus the cases where it induced ovulation but no pregnancy (28.8% versus 58.1%, P<0.003). Discussion and conclusionFertiloscopy results are comparable with those of laparoscopy, which suggests an advantage to this technique in terms of cost, comfort, and length of hospital stay. No usable in practice patient selection criteria could be highlighted. The study suggests that the absence of ovulation after drilling may be a direct indication for IVF.

Eficiência da mensuração de progesterona salivar para identificar a ovulação em cadelas

Several authors have emphasized the importance of monitoring estrous cycle in bitches and mentioned technique examples of how it can be done. The aim of this study was to evaluate the salivary progesterone quantification technique in order to identify ovulation in this species. To compound the experimental group, 13 bitches of different breeds (no specific breed, English Bulldog, Bernesse Mountain Dog)and different ages (from 11 months to 9 years old) were used. Blood and saliva samples were collected simultaneously in all animals, starting about the first day of proestrus clinical signs. Salivary samples were collected with a specific commercial device (Salivette®). This method was effective, since it has become possible to obtain enough volume in almost all samples to quantify salivary progesterone (100 μLfor duplicate quantification). Serum progesterone was quantified by radioimmunoassay and salivary progesterone by enzyme immunoassay, both of them with commercial kits. There was an increasing, linear and positive correlation between salivary and serum progesterone (r=0.704; p<0.0001) in bitches. One of the animals had an anovulatory cycle, in which, for 13 days, seric progesterone levels were maintained between 1.67 and 3.76 ng/mL and salivary progesterone levels were maintained between 19.55 and 236.77 pg/mL. It was concluded that salivary progesterone levels measured by enzyme immunoassay is a technique that can be used to evaluate the presence or absence of ovulation in bitches.

Occurrence of an Intersexual Blacktip Shark in the Northern Gulf of Mexico, with Notes on the Standardization of Classifications for This Condition in Elasmobranchs

AbstractAn intersexual Blacktip Shark Carcharhinus limbatus with a testis, immature female reproductive tracts (embedded), and claspers was caught in the Gulf of Mexico. Histology of the single gonad revealed that all stages of spermatogenesis were occurring; however, the absence of ovaries and a male duct system suggests that neither sex would have been functional in this individual. Intersexuality has been reported in 17 families and 36 species of elasmobranchs. The degree to which the different sexes are present in a given individual is often difficult to categorize by normal hermaphroditic standards, as this is typically an anomalous presentation in elasmobranchs. Therefore, this report provides three categories for classification (basic, incomplete, and complete intersexuality) to standardize terminology and allow for more precise comparisons to be made among elasmobranch examples. Basic intersexuals have gonadal tissue of only one sex and a combination of other male and female characters with neither or only one sex being complete. Incomplete intersexuals have gonadal tissue of both sexes and a combination of other male and female characters; however, neither or only one sex is complete. Complete intersexuals have claspers as well as gonadal tissue and tracts for both sexes. The majority of the reported intersexual elasmobranchs, including the shark described here, are basic intersexuals.Received September 30, 2012; accepted April 17, 2013

Expression of Insulin-like Growth Factor-I in Uterus is Ovarian Steroid Dependent: An in situ Immunohistochemical Study in Rat

Objective To study the immunohistochemical localization of insulin-like growth factor-I (IGF-I) in rats' uteri to determine if expression of the growth factor is ovarian steroid dependent. Method The study was carried out in presence and absence of ovary in situ of non pregnant females and during early gestation (day 1 to day 5.5). Cyclic females were tested to observe the effect of native steroids on IGF-I expression. Adult females were ovariectomized (OVX) and injected (s.c) with estradiol-17β in a dose of 0.1 μg/ml per day for three consecutive days at interval of 24 h prior to the collection of uterine horns. During the early pregnancy, studies were carried out on day 3.5 and day 5.5 of geatation respectively to determine the steroids' effects during pre- and post-implantation period. Tamoxifen was administered (s.c) in a dose of 250 μg/ml per day from day 1 to day 3 of gestation while, the prostaglandin F 2α (PGF 2α ) was administered (s.c) from day 3 of gestation onward for three consecutive days at interval of 24 h in a dose of 150 μg/ml per day. Expression of IGF-I was immunohistochemically localised using IGF-I antibody in paraffin embedded sections. Results IGF-I was expressed in rat uterus during estrus phase as well as during pre and post-implantation period. The ovariectomized females' uteri lost the expression of IGF-I. Exogenous administration of tamoxifen and PGF 2α reduce the expression of the growth factor. Conclusion Expression of IGF-I in rat uterus during cyclic stage and early gestation depends upon the availability of circulating estrogen and progesterone. Uterine expression of IGF-I can be modulated by manipulating circulating ovarian steroid either during cyclic stage or during gestation.

Function and innervation of the locus ceruleus in a macaque model of Functional Hypothalamic Amenorrhea

A body of knowledge implicates an increase in output from the locus ceruleus (LC) during stress. We questioned the innervation and function of the LC in our macaque model of Functional Hypothalamic Amenorrhea, also known as Stress-Induced Amenorrhea. Cohorts of macaques were initially characterized as highly stress resilient (HSR) or stress-sensitive (SS) based upon the presence or absence of ovulation during a protocol involving 2 menstrual cycles with psychosocial and metabolic stress. Afterwards, the animals were rested until normal menstrual cycles resumed and then euthanized on day 5 of a new menstrual cycle [a] in the absence of further stress; or [b] after 5days of resumed psychosocial and metabolic stress. In this study, parameters of the LC were examined in HSR and SS animals in the presence and absence of stress (2×2 block design) using ICC and image analysis. Tyrosine hydroxylase (TH) is the rate-limiting enzyme for the synthesis of catecholamines; and the TH level was used to assess by inference, NE output. The pixel area of TH-positive dendrites extending outside the medial border of the LC was significantly increased by stress to a similar degree in both HSR and SS animals (p<0.0001). There is a significant CRF innervation of the LC. The positive pixel area of CRF boutons, lateral to the LC, was higher in SS than HSR animals in the absence of stress. Five days of moderate stress significantly increased the CRF-positive bouton pixel area in the HSR group (p<0.02), but not in the SS group. There is also a significant serotonin innervation of the LC. A marked increase in medial serotonin dendrite swelling and beading was observed in the SS+stress group, which may be a consequence of excitotoxicity. The dendrite beading interfered with analysis of axonal boutons. However, at one anatomical level, the serotonin-positive bouton area was obtained between the LC and the superior cerebellar peduncle. Serotonin-positive bouton pixel area was significantly higher in HSR than SS animals (p<0.04). There was no change in either group after 5days of moderate stress. The ratio of serotonin/TH correlates with ovarian estrogen production with a sensitivity×stress interaction. Therefore, it appears that the serotonin system determines stress sensitivity and the NE system responds to stress. We hypothesize that elevated NE with low serotonin functionality ultimately leads to stress-induced infertility. In contrast, high serotonin functionality maintains ovulation in the presence of stress even with elevated NE.

Dynamics of ovarian follicles in Tupinambis merianae lizards

Follicular dynamics of Tupinambis merianae lizards was analyzed by means of ultrasound examination and radio frequency identification, during three con- secutive reproductive periods, both in reproduction and in sexual isolation. Series of follicular development which ended in ovulation, and series of follicular develop - ment without ovulation, followed by a regression process, were observed, as well as a combination of both. Ovulation was found to be strongly dependent on mating con- summation. In 34% of the cases in which follicular development ended with ovula- tion, and hence oviposition, follicles showed a steady and uniform growth up to the periovulatory period, also acquiring a mild echogenicity. In the absence of ovulation (66% of cases), follicular development showed two patterns: a short and a long-term anovulatory follicular cycle. In the first pattern, follicles showed limited growth and a non-echoic aspect, which suggests a previtellogenic condition. In the second pattern, follicles exhibited a growth and echogenicity similar to periovulatory ones, presum- ably attaining a vitellogenic stage. In addition, follicular development in reproduc - ing females was superior to that of sexually isolated females. Follicular development, ovulation, and follicular regression appeared to constitute generalized events affecting most, if not all, of the recruited follicles.

A reproductive option for women with Turner's syndrome.

In the past, management of congenital absence of ovaries in women with Turner's syndrome (TS) was limited to replacement of ovarian hormones to initiate pubertal development. Until recently, adoption or stepparenting were the only parenting options. However, with new developments in assisted reproduction, women with TS may be able to successfully complete pregnancy and childbearing. There are specific nursing considerations for children and adolescents to follow: anticipatory guidance regarding sexual development; encouraging discussions of the range of options that are available for women with TS regarding reproduction; and assisting these children and adolescents in understanding the benefits and limitations associated with one reproductive option, in vitro fertilization.

Measurement of serum anti-Müllerian hormone concentration in female dogs and cats before and after ovariohysterectomy

Anti-Müllerian hormone (AMH), or Müllerian inhibitory substance, is a hormone that is best known for its production by fetal testes in mammals and as the inhibitor of Müllerian (paramesonephric) duct development in males. However, following the development of the Müllerian ducts into the oviduct, uterus, and upper vagina in female mammals, the ovaries produce AMH, which can be found in measureable amounts within the peripheral circulation, especially in adults. The ovaries appear to be the sole source of AMH in the circulation; therefore, it may be a useful marker in clinically relevant situations when an assessment of the presence or absence of ovaries or ovarian remnants in dogs and cats is important. To that end, a commercially available, human-based assay was evaluated for the measurement of AMH in dogs and cats. A preliminary assessment involved a single test on a set of serum samples from dogs that were submitted to a diagnostic endocrinology laboratory for other tests. Favorable preliminary results led to a more formal assessment of the assay using serum samples from dogs and cats with the presence or absence of the ovaries known by surgical confirmation. Overall, a single measurement of serum AMH concentration was highly effective at distinguishing ovariohysterectomized from intact adult animals. In addition, the assay also accurately identified several cases of ovarian remnant syndrome.

Circulating dehydroepiandrosterone sulfate levels in women who underwent bilateral salpingo-oophorectomy during the menopausal transition

A rise in circulating dehydroepiandrosterone sulfate (DHEAS) concentration occurs during the menopausal transition (MT) that is ovarian stage related but not age related. The objective of this study was to determine the source of the rise in circulating DHEAS. Circulating DHEAS concentrations in women who had undergone bilateral salpingo-oophorectomy (BSO) were compared with the pattern of circulating DHEAS in women who progressed through the MT naturally. Annual serum samples from the Study of Women's Health Across the Nation (SWAN) over a 10-year study period were used. From 1,272 women in the SWAN cohort who were eligible for longitudinal evaluation of DHEAS annual samples, 81 underwent BSO during the premenopausal or early perimenopausal stage of the MT and were potentially available for study. Of these 81 BSO participants, 20 had sufficient annual samples for evaluation of the post-BSO trajectory of circulating DHEAS. SWAN women not having used hormone therapy previously and those with intact ovaries were compared with women who underwent a BSO immediately after a premenopausal or early perimenopausal annual visit. There were no interventions, and circulating concentration of DHEAS was the main outcome. A detectable rise in DHEAS was observed in 14 (70%) of the 20 BSO women, which is similar to the proportion (85%) of women with intact ovaries who had a detectable DHEAS rise. The mean rise in DHEAS (5%-8%) was similar in both BSO and non-BSO women. The MT rise in DHEAS (5%-8%) occurring in the absence of ovaries is largely of adrenal origin.

Sex differences in hypothalamic astrocyte response to estradiol stimulation

BackgroundReproductive functions controlled by the hypothalamus are highly sexually differentiated. One of the most dramatic differences involves estrogen positive feedback, which leads to ovulation. A crucial feature of this positive feedback is the ability of estradiol to facilitate progesterone synthesis in female hypothalamic astrocytes. Conversely, estradiol fails to elevate hypothalamic progesterone levels in male rodents, which lack the estrogen positive feedback-induced luteinizing hormone (LH) surge. To determine whether hypothalamic astrocytes are sexually differentiated, we examined the cellular responses of female and male astrocytes to estradiol stimulation.MethodsPrimary adult hypothalamic astrocyte cultures were established from wild type rats and mice, estrogen receptor-α knockout (ERKO) mice, and four core genotype (FCG) mice, with the sex determining region of the Y chromosome (Sry) deleted and inserted into an autosome. Astrocytes were analyzed for Sry expression with reverse transcription PCR. Responses to estradiol stimulation were tested by measuring free cytoplasmic calcium concentration ([Ca2+]i) with fluo-4 AM, and progesterone synthesis with column chromatography and radioimmunoassay. Membrane estrogen receptor-α (mERα) levels were examined using surface biotinylation and western blotting.ResultsEstradiol stimulated both [Ca2+]i release and progesterone synthesis in hypothalamic astrocytes from adult female mice. Male astrocytes had a significantly elevated [Ca2+]i response but it was significantly lower than in females, and progesterone synthesis was not enhanced. Surface biotinylation demonstrated mERα in both female and male astrocytes, but only in female astrocytes did estradiol treatment increase insertion of the receptor into the membrane, a necessary step for maximal [Ca2+]i release. Regardless of the chromosomal sex, estradiol facilitated progesterone synthesis in astrocytes from mice with ovaries (XX and XY-), but not in mice with testes (XY-Sry and XXSry).ConclusionsAstrocytes are sexually differentiated, and in adulthood reflect the actions of sex steroids during development. The response of hypothalamic astrocytes to estradiol stimulation was determined by the presence or absence of ovaries, regardless of chromosomal sex. The trafficking of mERα in female, but not male, astrocytes further suggests that cell signaling mechanisms are sexually differentiated.

The Nuclear Receptor Nr5a2 Coordinates Ovulation and Female Fertility in Granulosa Cells of Different Stages of Follicle Maturation in Mice.

The nuclear receptor Nr5a2 (liver receptor homolog-1) is expressed in the ovary, exclusively in granulosa and luteal cells. Germline ablation of Nr5a2 causes embryo lethality, while conditional disruption beginning with the primary follicle stage by means of Nr5a2-floxed and Amhr2Cre/+ mice results in failure of ovulation and luteinization. We hypothesized that Nr5a2 modulates the events leading to development of a preovulatory follicle and its consequent ovulation in a temporal sequence. To test this, granulosa-specific mutants (hereafter characterized as Nr5a2gc-/-) were generated by crossing Nr5a2-floxed mice with mice expressing the Cyp19-Cre, thereby excising Nr5a2 at the antral (tertiary) follicle stage. Similar to Amhr2-Cre driven disruption of Nr5a2, no litters were born to Nr5a2gc-/- females, while Nr5a2gc+/+ females were fertile (six-month breeding trial; n = 5 per genotype). In contrast to Amhr2-Cre driven disruption of Nr5a2, the pattern of estrous cyclicity and serum progesterone appeared to be normal in Nr5a2gc-/- mice compared to Nr5a2gc+/+ mice (n = 5). Likewise, ovarian morphology indicated that antral follicles were present but that cumulus expansion was distinctly absent in Nr5a2gc-/- follicles. In further contrast to Amhr2-Cre driven disruption of Nr5a2, Nr5a2gc-/- ovaries in our study had corpus luteum-like structures that appeared to be comprised of luteinized theca cells surrounding degenerating granulosa cells. Entrapped oocytes were found within these structures. Thus, it was apparent that interdiction of Nr5a2 expression using Cyp19Cre/+ in antral follicles enabled further maturation of follicles than did excision by Amhr2 Cre/+. It also allowed the development of a luteal-like structure in the absence of ovulation. We conclude that Nr5a2 differentially regulates ovarian folliculogenetic and ovulatory processes in granulosa cells of small and antral follicles. Supported by CIHR grant FRN 11018. (poster)