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Oxytocin secretion by bovine granulosa cells: effects of stage of follicular development, gonadotropins, and coculture with theca interna.

Oxytocin (OT) has been detected in ruminant preovulatory follicles. Bovine granulosa cells express the oxytocin/neurophysin I (OT/NP-I) gene and secrete OT in vitro. The objective of this study was to determine the developmental pattern of OT secretion by bovine follicle cells as they differentiate during the follicular phase and the preovulatory follicle approaches ovulation. Holstein heifers were injected with prostaglandin F2 alpha in midluteal phase to induce luteal regression and initiate a follicular phase. The ovary bearing the preovulatory follicle was obtained by ovariectomy early in the follicular phase, in midfollicular phase, or late in the follicular phase, after the LH/FSH surge (n = 4 heifers per group). Theca interna and granulosa cells were isolated and cultured for 5 days, individually or in coculture, in defined or serum-containing medium and with or without LH (300 ng/ml) or FSH (300 ng/ml). Media were collected and replaced completely every 24 h, and OT secreted into the media was measured by RIA. Granulosa cells isolated at all three time points during the follicular phase secreted measurable amounts of OT. However, total OT secretion by granulosa cells isolated after the LH/FSH surge was 18.9-fold (defined medium) to 64.8-fold (serum-containing medium) higher than OT secretion by granulosa cells isolated early in the follicular phase, and 14.6-fold (defined medium) to 170-fold (serum-containing medium) higher than OT secretion by granulosa cells isolated in midfollicular phase. Granulosa cells isolated before the LH/FSH surge responded to the addition of LH or FSH to the culture medium with an increase in OT secretion. Cocultures of granulosa cells and theca interna isolated before the LH surge secreted more OT than cultures of granulosa cells alone. When cells were isolated early in the follicular phase the effect of coculture was more than additive, but the effect of coculture was only additive when follicles were obtained in midfollicular phase. OT secretion by granulosa cells isolated after the LH/FSH surge was not affected by gonadotropins or by coculture with theca interna. In contrast to results for granulosa cells, theca interna secreted only small and variable amounts of OT, and responses to LH were inconsistent. These findings suggest that OT detected in cultures of theca interna may be produced by small and variable numbers of granulosa cells contaminating the theca interna preparation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Follicular development: lessons learned from human in vitro fertilization.

In vitro fertilization has offered new insights into our understanding of ovulation induction, folliculogenesis, and luteal phase events. This new information is provided by the ability to precisely study these cycles in a frequent and sequential fashion through the use of peripheral blood markers, ultrasound evaluation, and follicular fluid constituents and cell culture techniques, as well as direct observation of the oocyte, fertilization, and cleavage. In these stimulated cycles the follicular phase serum estradiol levels in conjunction with ultrasound were evaluated; a poor correlation was shown between follicle size and number and estrogen production. This distinct dyssynchrony suggests the recruitment of a number of cohorts of follicles in each stimulated cycle. From the biochemical markers in follicular fluid, cyclic adenosine monophosphate has a distinct predictive value in regard to pregnancy in in vitro fertilization-embryo transfer cycles. In the luteal phase, the mass effect of aspiration of great numbers of granulosa cells, the effect of supplemental progesterone, and the influence of high follicular phase estradiol levels remain controversial and, therefore, a less clear cut pattern emerges. Variations in the protocol have not greatly improved the major problems of folliculogenesis associated with ovulation induction and an in vitro fertilization-embryo transfer program, that is, follicular asynchrony and luteal phase deficiency.

Body Fluids↗

Effects of metoclopramide-induced hyperprolactinemia during early follicular development on human ovarian function.

Nine healthy women, aged 25 to 36 yr, were treated with metoclopramide (MC) (10 mg orally three times daily) from the first to the sixth day of their cycle (treatment A) for two successive cycles (n = 18) and six of these women later received MC from -3 to the fifth day of the menstrual cycle (treatment B) during one or two cycles (n = 10), to investigate the effects of hyperprolactinemia during the early phase of ovarian follicular growth. Comparisons were performed with control cycles in the same women. The treatment cycles were characterized by low serum concentrations of LH during the early follicular phase and at midcycle, low early follicular phase serum testosterone (T) levels and high luteal phase T and free T index values, with no significant differences between A and B treatment modalities. We classified the treatment cycles into two categories, seriously disturbed and normal or only slightly disturbed, on the basis of ultrasonographic findings and midcycle estradiol (E2) and luteal phase progesterone (P) concentrations. Folliculogenesis was seriously disturbed in 11 of the 28 treatment cycles (39%). During these cycles, midcycle serum LH and the LH to FSH ratio were lowered, luteal phase LH and FSH increased, midcycle E2 and luteal phase P and the P to E2 ratio decreased, luteal phase T and the free T index and androstenedione increased, and luteal phase 5 alpha-dihydrotestosterone decreased. During the early follicular phase and at midcycle the ratios of T to E2 and androstenedione to E2 were increased, and at midcycle and during the luteal phase of the cycle the ratio of T to 5 alpha-dihydrotestosterone was increased. These changes in steroid hormones were probably of ovarian origin since the serum concentrations of dehydroepiandrosterone sulfate and sex hormone-binding globulin were similar in seriously disturbed and control cycles. Four of the nine study subjects were hyperprolactinemia sensitive (disturbed folliculogenesis) and five hyperprolactinemia resistant (no disturbance in folliculogenesis). During the control cycles the hyperprolactinemia-sensitive women had significantly higher serum concentrations of T than the other women. The present observations indicate that hyperprolactinemia may impair the development of the ovarian follicles during their recruitment period, especially in women with relatively high serum T levels.

Adult↗

An analysis of the effects of increasing doses of ionizing radiation to the exteriorized rat ovary on follicular development, atresia, and serum gonadotropin levels.

There is increasing interest in the effects of environmental and therapeutic agents on the reproductive system, in particular, the ovary. To study the effects of controlled doses of ionizing radiation to the ovary, Sprague-Dawley rats had their ovaries exteriorized and subjected to increasing doses of radiation. There was a significant increase in ovarian follicular atresia, a significant increase in serum follicle-stimulating hormone levels, but no change in serum luteinizing hormone levels. This experimental protocol may facilitate the testing putative radioprotectants.

Animals↗

Monocrotophos induced dysfunction on estrous cycle and follicular development in mice.

Monocrotophos a organophosphate pesticide was administered orally at doses of 1.6, 3.3, 6.6, 10 and 13 mg/kg body weight/day to normal virgin Swiss albino mice for 30 days. The vaginal smear and body weight of the mice were recorded daily and mice were sacrificed on 31st day. The ovaries from each animal was serially sectioned and stained for follicular studies. Estrous cycle was affected by showing a significant decrease in the number of estrous cycle and duration of proestrus, estrus and metestrus with concomitant significant increase in the duration of diestrus in all the treated groups, except with 1.6 mg/kg body weight/day monocrotophos treated group. There were significant decrease in the small, medium, large and total number of healthy follicles and increase in the medium, large and total number of atretic follicles with 6.6, 10 and 13 mg/kg body weight/day monocrotophos treatment. However, there were no significant change in the number of healthy and atretic follicles with 1.6 and 3.3 mg/kg/bodyweight/day monocrotophos treatment. There was no change organs weight except for a significant decrease in weight of the ovary with 3.3, 6.6, 10 and 13 mg/kg body weight/day and uterus and body weight with 10 and 13 mg/kg body weight/day monocrotophos treatment. Interruption in estrous cycle, decrease in healthy follicles and increase in atretic follicles may be due to harmonal imbalance or toxic effects of monocrotophos, which adversely effects reproductive function, as it has also analgesic and sedative action.

Animals↗

Immunolocalization of steroidogenic cells in small follicles of the chicken ovary: anatomical arrangement and location of steroidogenic cells change during follicular development.

Previous anatomical and histochemical studies suggested that interstitial cells were the only steroidogenic cells in the theca layer of small follicles of the chicken ovary. However, the precise cellular site of steroid production in the small follicles is not certain. Therefore, our goal was to identify steroidogenic cells in small follicles (less than 10 mm in diameter) of the chicken ovary which have not entered the follicular hierarchy by localizing steroidogenic enzymes with immunocytochemistry. Polyclonal antisera used were anti-cholesterol side-chain-cleavage cytochrome P450 (P450scc), anti-17 alpha-hydroxylase cytochrome P450 (P450c17), and anti-aromatase cytochrome P450 (P450arom) for pregnenolone-, androgen-, and estrogen-producing cells, respectively. Ovaries were collected 2 hr after oviposition and embedded in Paraplast after fixation with 4% paraformaldehyde, 10% formaldehyde, or Bouin's solution. Tissues were sectioned (4-6 microns) and sections were mounted on poly-L-lysine coated slides. Sections were incubated overnight at room temperature with each specific antiserum raised in rabbits against cytochrome P450 steroidogenic enzymes or normal rabbit serum as a control and were immunostained with an avidin-biotin-peroxidase complex. Immunoreactivity for the P450 enzymes was absent in the granulosa layer but was present in the theca layer of the small follicles (less than 10 mm in diameter). Interstitial cells in the single theca layer of cortical follicles embedded in the ovarian cortex (less than 1 mm in diameter) contained P450scc and P450c17. Cells which contained P450arom, identified as aromatase cells, surrounded the interstitial cells in the theca layer.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Evaluation of stimulated cycles with multiple follicular development but low oocyte retrieval.

Factors that may explain a low oocyte recovery rate by laparoscopy were examined. Two different groups of women were evaluated. Group A (n = 56) had zero or one oocyte recovered, despite the aspiration of three or more follicles. Group B (n = 36), had oocytes recovered from more than 75% of punctured follicles. Group B showed significant increases in total estradiol (E2) values during the follicular phase (P less than .05), E2 peak levels (P less than .001), and number of patients with E2 rise the day after hCG administration (P less than .001) compared with group A. However, the number and size of the follicles as determined by ultrasound during the last two pre-oocyte recovery days were not significantly different. On the day of laparoscopy, there was a significant decrease in the number of follicles in group A versus B (P less than .001). In addition, the number of patients with a decrease in E2 values the day of laparoscopy was significantly higher in group A (P less than .001). Together these factors suggest an increased incidence of ovulation prior to laparoscopy in group A. The extent and severity of adhesions were graded as absent, mild or moderate, and severe. No difference was observed between groups. Moreover, comparing the number of follicles visualized before laparoscopy and the number of follicles punctured, the ovarian accessibility was not different (76.6% vs. 79.5%). This suggests that a decrease in access to the ovaries was not the cause of poor oocyte recovery. It is concluded that differences in recovery rates, then, are best attributed to the endocrine milieu of the cycle.

Adult↗

Plasma concentrations of inhibin a and follicle-stimulating hormone differ between cows with two or three waves of ovarian follicular development in a single estrous cycle.

Patterns of ovarian follicle development were monitored daily in Holstein-Friesian cows that had two (n = 4) or three (n = 4) waves of ovarian follicle development during a single estrous cycle. The plasma from daily blood samples was used in assays for inhibin A, FSH, progesterone, and estradiol-17beta. Mean cycle lengths for cows with two and three waves were 21.8 and 25.3 days, respectively (P < 0.02). Although the average number of follicles >3-mm diameter on each pair of ovaries was similar for two- and three-wave cows on Days 2, 3, and 4 (Day 0 = day of ovulation; 8.6 vs. 9.6 follicles), there were more follicles >6-mm diameter on the ovaries of cows with two waves on Days 3 and 4. This difference was associated with a shorter interval from wave emergence to peak concentrations of inhibin A during the first wave in two-wave cows (2.0 vs. 3.8 days; P = 0.03) and with higher peak concentrations (474 vs. 332 pg/ml; P = 0.03). Differences in peak FSH concentrations were not significant (1.7 vs. 1.3 ng/ml; P = 0.10) and were inversely related to inhibin A concentrations. The peak concentrations of inhibin A and FSH in the second nonovulatory wave in the three-wave cows were similar to the low concentrations measured in the first wave (292 vs. 332 pg/ml of inhibin A, 1.3 vs. 1.3 ng/ml of FSH; P > 0.20). Average peak concentrations of inhibin A and FSH were similar during the ovulatory wave for cows with either two or three waves in a cycle (432 vs. 464 pg/ml of inhibin A, 2.3 vs. 2.1 ng/ml of FSH; P > 0.3). The lower concentrations of FSH during the emergence of the first follicular wave in cows with three-wave cycles may have reduced the rate of development of some of the follicles and reduced the concentrations of inhibin A. This pattern of lower concentrations of FSH and inhibin A was repeated in the second nonovulatory wave but not in the ovulatory wave. Subtle differences in the concentrations of these two hormones may underlie the mechanism that influences the number of waves of ovarian follicle development that occur during the bovine estrous cycle.

Animals↗

Follicular development, ovulation, fertilization and fetal development in tenrecs (Tenrec ecaudatus).

Reproduction in female tenrecs was studied on Praslin Island (4 degrees 20'S, 55 degrees 45'E) in the Seychelles from November 1977 to September 1980. Dissection and histological examination of reproductive tracts revealed that each ovary is encapsulated in a bursa. Polyovular follicles were abundant and contained up to 5 oocytes. The occurrence of more implanted fetuses than corpora lutea (CL) indicated successful polyovuly in 25% of pregnancies. No antrum was observed during follicular growth at oestrus, and follicles were relatively small at maturation, reaching a maximum diameter of 570 microns. Ovulation involves a gentle extrusion of the granulosa and ovum into the periovarian space. Spermatozoa were abundant in the female reproductive tract including the periovarian space at oestrus. Spermatozoa penetrated the loosely-packed theca of mature follicles and were present in CL, indicating that intrafollicular fertilization may occur. The relatively small CL formed by eversion, reaching a maximum size after implantation. Fusion of up to four CL occurred in the ovaries of 41% of pregnant females. Polyovulation in the tenrec was confirmed by the occurrence of 10.4 +/- 0.5 (mean +/- s.e.m.) CL and 9.7 +/- 0.5 (mean +/- s.e.m.) implantations. Resorption occurred in 74% of 19 dissectable pregnancies, occurring in both uterine horns in 26% of pregnancies. Coefficients of variation in weights of fetuses in each litter were 10.0-26.8%, with the largest value corresponding to 273% variation in fetus weights. Litter size in the Seychelles tenrecs was smaller than in the same species in Madagascar (17.1 +/- 1.9 implantations) where the tenrec is native.

Animals↗

Expression of anti-Müllerian hormone mRNA during gonadal and follicular development in the brushtail possum (Trichosurus vulpecula).

The ontogeny of anti-Müllerian hormone (AMH) gene expression in the brushtail possum during formation of the ovary and growth of follicles was examined using in situ hybridization. For comparative purposes, the expression pattern of AMH was also examined in the developing testis. In the female, AMH mRNA was observed in the ovary of 50% (3/6) of pouch young collected around the time of sexual differentiation of the gonad (Days 1-5): the signal was predominately localized to the inner-cortical and outer-medullary region of the ovary. Thereafter, AMH mRNA was not observed in the developing ovary until Days 78-113 of postnatal life when follicles first formed at the cortical-medullary boundary. At this time, AMH mRNA was observed in the cuboidal granulosa cells of some early growing (i.e. transitional) follicles and in the granulosa cells of primary follicles. Thereafter, AMH mRNA was present in granulosa cells at all subsequent stages of follicular growth (i.e. primary through antral), but not in preovulatory follicles. In all cases, once follicles had formed, AMH mRNA was limited to the granulosa cells and was not observed in the surface epithelium, stromal cells, oocytes, theca, corpus luteum, medullary cords, rete or interstitial glands. In the possum testis, Sertoli cells strongly expressed AMH around the time of sexual differentiation of the gonad, but expression decreased to very low levels in adults, suggesting that AMH plays a similar role in brushtail possums to that observed in other mammalian species. In conclusion, localization of mRNA for AMH exclusively to granulosa cells of growing follicles in the brushtail possum is consistent with a central role for this hormone in control of granulosa cell function in marsupials. In addition, expression of AMH in the developing ovary around the time of morphological sexual differentiation raises intriguing questions regarding the possible role of AMH at this time.

Animals↗

Gonadotrophin control of follicular development.

In order to investigate the endocrine requirements for induction of follicle maturation, ovulation and luteal function we have measured plasma LH and FSH concentrations in 109 cycles induced by treatment with LHRH in 25 women with amenorrhoea of diverse aetiology. The major clinical and endocrine subgroupings were polycystic ovarian disease (PCO), Kallmann's syndrome, weight related amenorrhoea and hyperprolactinaemia. By analysis of variance of the LH and FSH concentrations obtained three times per week in the follicular phase in 77 ovulatory cycles (including 24 conception cycles), we found that in women with PCO the mean LH concentration was 19.5 IU/l. In hyperprolactinaemia and secondary amenorrhoea of non-specific aetiology the mean LH concentration was 11.6 IU/l and in patients with hypogonadotrophic hypogonadism and weight-related amenorrhoea it was 7.2IU/l. These mean LH concentrations were significantly different from each other (P less than 0.001). We speculate that the high LH concentrations in the follicular phase may impair the final stages of oocyte maturation and so contribute to the infertility of these patients. FSH concentrations in the follicular phase were lower in patients with hypogonadotrophic hypogonadism and weight-related amenorrhoea than in other groups. Although the differences were statistically significant (P less than 0.001) the difference was small (mean FSH in hypogonadotrophic hypogonadism and weight-related amenorrhoea 4.3 IU/l vs 6.3 IU/l in the others) and of uncertain biological significance. During the luteal phase, no differences between any of the groups in LH and FSH concentrations were found.

Adult↗

The role of transforming growth factor-beta (TGF-beta) during ovarian follicular development in sheep.

BACKGROUND: Recently, several members of the transforming growth factor-beta (TGF-beta) superfamily have been shown to be essential for regulating the growth and differentiation of ovarian follicles and thus fertility. METHODS: Ovaries of neonatal and adult sheep were examined for expression of the TGF-betas 1-3 and their receptors (RI and RII) by in situ hybridization using ovine cDNAs. The effects of TGF-beta 1 and 2 on proliferation and differentiation of ovine granulosa cells in vitro were also studied. RESULTS: The expression patterns of TGF-beta 1 and 2 were similar in that both mRNAs were first observed in thecal cells of type 3 (small pre-antral) follicles. Expression of both mRNAs continued to be observed in the theca of larger follicles and was also present in cells within the stroma and associated with the vascular system of the ovary. There was no evidence for expression in granulosa cells or oocytes. Expression of TGF-beta 3 mRNA was limited to cells associated with the vascular system within the ovary. TGFbetaRI mRNA was observed in oocytes from the type 1 (primordial) to type 5 (antral) stages of follicular growth and granulosa and thecal cells expressed this mRNA at the type 3 (small pre-antral) and subsequent stages of development. The TGFbetaRI signal was also observed in the ovarian stroma and vascular cells. In ovarian follicles, mRNA encoding TGFbetaRII was restricted to thecal cells of type 3 (small pre-antral) and larger follicles. In addition, expression was also observed in some cells of the surface epithelium and in some stromal cells. In granulosa cells cultured for 6 days, both TGF-beta 1 and 2 decreased, in a dose dependent manner, both the amount of DNA and concentration of progesterone. CONCLUSION: In summary, mRNA encoding both TGF-beta 1 and 2 were synthesized by ovarian theca, stroma and cells of the vascular system whereas TGF-beta 3 mRNA was synthesized by vascular cells. Luteinizing granulosa cells also responded to both TGF-beta 1 and beta 2 in vitro. These findings in sheep are consistent with TGF-beta potentially being an important autocrine regulator of thecal cell function and possibly a paracrine regulator of ovarian cell function at various development stages.

Aging↗

Immunolocalization of transforming growth factor-beta1 during follicular development and atresia in the mouse ovary.

In each estrous cycle not all follicles recruited grow to ovulate, as some degenerate through the process of atresia. Apoptosis is the mechanism underlying follicle atresia. TGF-beta1 has been implicated in the induction and promotion of apoptosis in many cell types and it is expressed in the ovary. In this study immunohistochemistry was used to localize TGF-beta1 in order to correlate the growth factor expression with morphological follicular atresia during diestrus in mice. Small and medium sized follicles had no staining for TGF-beta1 in the granulosa or theca cell layer. Weak to moderate TGF-beta1 expression was present in the theca cells of both large healthy and atretic antral follicles. Large healthy antral follicles showed weak granulosa staining but this was not observed in atretic follicles. Strong TGF-beta1 staining was present in the interstitial, corpus luteum and oocytes of all follicle stages. These results suggest that in the mouse TGF-beta1 promote follicular growth and differentiation rather than follicular atresia.

Animals↗

Effect of boar contact on follicular development and on estrus expression after weaning in primiparous sows.

Boar contact can induce ovarian activity, advance estrus and stimulate estrous behavior in sows. High amounts of boar contact can, however, suppress estrous behaviour. The present study with primiparous sows was designed to compare sows that had contact with a teaser boar during detection of estrus, with sows that had no boar contact at all. Number of sows detected in estrus within 9 d after weaning, onset and duration of estrus, follicular dynamics and timing of ovulation were studied. Boar contact increased the number of sows that ovulated and showed estrus from 14 of 47 to 24 of 47 (P < 0.05). Average timing of ovulation was later for sows with boar contact (165 h vs 150 h after weaning). Duration of estrus, detected without a boar, was similar in the two groups. For the sows with boar contact, duration of estrus detected with a boar was longer than estrus detected without a boar (56 vs 38 h; P < .01). Follicular dynamics were not affected by boar contact; boar contact only increased the number of sows with ovulation. Ovulatory sows showed a larger increase in follicular diameter (P < 0.01) from weaning to Day 4 after weaning (from 2.3 to 5.4 mm) than anovulatory sows (from 2.5 to 4 mm). Anovulatory sows did not show follicular growth after Day 4. It is concluded that boar contact can increase the number of sows that ovulate and show estrus after weaning. Estrous behavior does not seem to be suppressed by contact with a teaser boar, compared to sows without boar contact.

Animals↗

Molecular aspects of hormone action in ovarian follicular development, ovulation, and luteinization.

As stated earlier, the mammalian ovary maintains the continuous development of follicles, but only a few are selected to ovulate and form corpora lutea. These processes are regulated primarily by the gonadotropins and involve specific, sequential changes in the function of theca cells and granulosa cells. Data from recent studies (summarized in Figure 3) show that specific genes are turned on or off at different stages of follicular growth in response to estradiol and different amounts of gonadotropins and cAMP. For example, mRNA for RII51 in granulosa cells and theca cells increases in association with small increased in cAMP but is markedly reduced by the LH surge and high cAMP. The content of mRNA for other kinase subunits, RI and C alpha, show little or no change during similar hormonal changes. In theca cells, mRNA for 17 alpha-hydroxylase increased and decreased in a manner similar to that for RII51. In contrast, levels of mRNA for P450scc increased only gradually in follicles but were markedly increased by the LH surge and high concentrations of cAMP and then appeared to be constitutively expressed in rat corpora lutea in a cAMP-independent manner. PGS and t-PA appear to follow yet another pattern: rapid induction by the LH surge followed by a rapid decline in association with ovulation. One major task for reproductive endocrinologists and molecular biologists now is to determine how low and high concentrations of cAMP act to turn on and turn off the expression of these specific genes at specific times during follicular maturation. A working model of the molecular events occurring in theca and granulosa cells of PO follicles is shown in Figure 4. LH acts on theca cells via cAMP ro regulate both P450scc and P450(17) alpha mRNA levels, leading to increased biosynthesis of androstenedione. The mechanisms by which cAMP acts in theca cells remain to be determined but appear to involve an increase in the content of RII51, P450scc, and P450(17) alpha. In granulosa cells, androstenedione is converted to estradiol by the aromatase P450 enzyme system. Estradiol, in turn, binds to estradiol receptors present in these cells and may thereby regulate gene expression. However, despite the presence of estradiol and estradiol receptors, little or no effect of estradiol is observed unless FSH acts via the FSH receptor to increase intracellular concentrations of cAMP. In a manner not yet understood, cAMP appears to enhance the actions of estradiol.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Effect of progestogen therapy on follicular development, related hormone concentrations and fertilization in vitro in unstimulated cycles and unexplained and endometriosis-associated infertility.

Evidence of pituitary-ovarian dysfunction in unexplained and endometriosis-associated infertility has been reported previously. Hormone-suppressive therapy is often used in an attempt to improve fertility, although benefits have not been proven. Our study examines the effect of progestogen (medroxyprogesterone acetate) treatment on women with endometriosis-associated and unexplained infertility, compared with women with tubal damage as functional controls. Pre-ovulatory follicular size and serum and follicular fluid hormone concentrations were measured, and oocyte collection and in-vitro fertilization were attempted, in natural cycles totally unperturbed by exogenous gonadotrophins, for two cycles before and two cycles following treatment with medroxyprogesterone acetate for 2 months. In the endometriosis and unexplained infertility groups, compared with the tubal group, the treatment led to significant reductions in the integrated luteinizing hormone (LH) values (483 versus 664, 559 versus 762 and 864 versus 820 notional IU/l respectively). There were no changes in serum oestradiol or follicular fluid oestradiol, progesterone, follicle stimulating hormone or LH concentrations after treatment. The results suggest that progestogen therapy has no beneficial effect on the pituitary-ovarian dysfunction which contributes to endometriosis-associated and unexplained infertility.

Case-Control Studies↗

Effects of energy balance on follicular development and first ovulation in postpartum dairy cows.

As milk production has increased during the past four decades, conception rates in lactating cows have declined. Although reduced reproductive performance has been associated with high milk yields, measures of postpartum ovarian activity have been more closely related to energy balance. The relationship between daily energy balance and postpartum reproductive activity is confirmed by longer intervals to first ovulation in cows with greater body condition loss. Patterns in daily energy balance, such as improvement from nadir, have been correlated with enhanced follicular function and a shorter interval to first ovulation. Such observations are consistent with increased LH pulse frequency following the energy balance nadir in lactating dairy cows. Evidence indicates a primarily hypothalamic locus for the modulation of LH secretion during negative energy balance. Formation of follicular waves after parturition begins synchronously in response to increased FSH in the first week postpartum, and is typically not a limiting factor in reproductive recrudescence. Altered follicular responsiveness to gonadotrophic support through changes in metabolic hormones such as insulin-like growth factor I (IGF-I) and insulin may contribute to impaired function of dominant follicles early postpartum. Positive relationships between changes in energy balance, peripheral IGF-I and function of dominant follicles support the identification of IGF-I and the day of the energy balance nadir as metabolic modulators of postpartum ovarian activity in dairy cows.

Animals↗

Transient expression of SOX9 protein during follicular development in the adult mouse ovary.

SOX9 is an essential activating transcription factor that plays a critical role in Sertoli cell differentiation and subsequent testis cord formation. Cytoplasmic SOX9 is present in both sexes during early gonadal embryogenesis. While in males the protein is later translocated into the nucleus of pre-Sertoli cells, its expression is rapidly turned off in females. In mammalian male gonads, SOX9 activates the expression of anti-Müllerian hormone (AMH), a male hormone that initiates Müllerian ducts regression and that is also expressed in postnatal ovarian follicles. Here, we confirm that the SOX9 protein is not present in the immature ovary but also show that SOX9 is transiently expressed in the mature ovary depending on the follicular cycle. Indeed, SOX9 protein was found in the nuclear compartment of the inner cells of the theca interna cell layer which surrounds the pre-antral/antral follicles. In contrast, no expression was detected in the AMH expressing granulosa cells. While these findings exclude the possibility that SOX9 regulates AMH expression in the ovary, they show that SOX9 could nevertheless play a role in the developing follicle.

Animals↗