scholarly journals Dysregulation of Ovarian Follicular Development in Female Rat: LH Decreases FSH Sensitivity During Preantral-Early Antral Transition

Endocrinology ◽  
2013 ◽  
Vol 154 (8) ◽  
pp. 2870-2880 ◽  
Author(s):  
Makoto Orisaka ◽  
Katsushige Hattori ◽  
Shin Fukuda ◽  
Tetsuya Mizutani ◽  
Kaoru Miyamoto ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Polycystic Ovary ◽  
Follicular Development ◽  
Antral Follicle ◽  
Fsh Receptor ◽  
Mrna Levels ◽  
Female Rat ◽  
Preantral Follicle ◽  
Follicle Growth ◽  
Antral Follicles

Abstract Several clinical studies have shown a correlation of hypersecretion of LH and polycystic ovary syndrome (PCOS), infertility, and miscarriage in women, suggesting that chronically elevated LH impairs fertility. Growth arrest of small antral follicles in PCOS is also assumed to be associated with an abnormal endocrine environment involving increased LH stimulation, a hyperandrogenic milieu, and subsequent dysregulated FSH action in the ovarian follicles. In this study, we examined whether and how LH modulates follicular development and steroid production during preantral-early antral follicle transition by using a rat preantral follicle culture system. LH augments testosterone and estradiol production in preantral follicles via up-regulating mRNA abundance of CYP17A1 and CYP19A1. LH promotes rat preantral follicle growth, and the follicular size reaches that of early antral follicles in vitro, a response attenuated by the specific androgen receptor antagonist and a targeted disruption of androgen receptor gene. Sustained follicle stimulation by LH, but not by androgen, decreases FSH receptor mRNA levels and FSH receptor signaling and inhibits FSH-induced follicular growth. The data suggest that LH promotes preantral-early antral transition via the increased synthesis and growth-promoting action of androgen. However, chronic LH stimulation impairs FSH-dependent antral follicle growth by suppressing granulosa cell FSHR expression via the modulation of intraovarian regulators, including LH-induced thecal factors.

Recombinant FSH (Org32489) induces follicle growth and ovulation in the adult cyclic rat

1995 ◽  
Vol 144 (1) ◽  
pp. 39-47 ◽  
Author(s):  
W A van Cappellen ◽  
H M A Meijs-Roelofs ◽  
P Kramer ◽  
E C M van Leeuwen ◽  
R de Leeuw ◽  
...  
Keyword(s):  
Mating Behaviour ◽  
Follicular Development ◽  
Antral Follicle ◽  
Ovulation Rate ◽  
Corpora Lutea ◽  
Follicle Growth ◽  
Antral Follicles ◽  
Normal Number ◽  
Lhrh Antagonist ◽  
65 H

Abstract The effects of a single injection of recombinant human FSH (rhFSH; Org32489) on ovulation rate and timing and on antral follicle growth were studied in adult 5-day cyclic rats. Rats injected at 1700 h on dioestrus-2 with a dose of 10 IU rhFSH showed, on average, no increase in ovulation rate on the day of expected oestrus. However, an additional, precocious ovulation resulting in a normal number of corpora lutea 13·3±0·4, n=6) was found to take place on the night after injection, i.e. dioestrus-3. No mating behaviour, as shown by the absence of vaginal plugs the next morning, was observed at this ovulation. Follicle counts showed a loss of large antral follicles due to ovulation and increased numbers of healthy small antral follicles at 17 and 41 h after injection, indicating a decrease of atresia of growing follicles as well as additional recruitment of new antral follicles. The endogenous serum FSH concentration on the subsequent day of oestrus (65 h after the rhFSH injection) as well as recruitment of small antral follicles were lower in the rhFSH-treated rats than in saline-treated controls. The ovulation at oestrus, 48 h after the precocious, rhFSH-induced ovulation showed large differences in the number of oocytes between the rats in one treatment group. Similar results in terms of immediate ovulation induction were obtained by using a highly purified human urinary FSH preparation (i.e. metrodin). Furthermore, the direct induction of ovulation by rhFSH or metrodin could not be prevented by the injection of an LHRH antagonist. It was concluded that rhFSH can induce acute ovulation in rats, and stimulates follicular development directly or indirectly through increased FSH levels after ovulation. It induces antral follicle growth and decreases early atresia in small antral follicles. Journal of Endocrinology (1995) 144, 39–47

Fetal programming by androgen excess in rats affects ovarian fuel sensors and steroidogenesis

2019 ◽  
Vol 10 (6) ◽  
pp. 645-658 ◽  
Author(s):  
Giselle Adriana Abruzzese ◽  
Maria Florencia Heber ◽  
Fiorella Campo Verde Arbocco ◽  
Silvana Rocio Ferreira ◽  
Alicia Beatriz Motta
Keyword(s):  
Fetal Programming ◽  
Polycystic Ovary ◽  
Follicular Development ◽  
Female Offspring ◽  
Mrna Levels ◽  
Androgen Excess ◽  
Ovary Syndrome ◽  
Pregnant Rats ◽  
Reproductive Disorder ◽  
Main Factors

AbstractFetal programming by androgen excess is hypothesized as one of the main factors contributing to the development of polycystic ovary syndrome (PCOS). PCOS is more than a reproductive disorder, as women with PCOS also show metabolic and other endocrine alterations. Since both ovarian and reproductive functions depend on energy balance, the alterations in metabolism may be related to reproductive alterations. The present study aimed to evaluate the effect of androgen excess during prenatal life on ovarian fuel sensors and its consequences on steroidogenesis. To this end, pregnant rats were hyperandrogenized with testosterone and the following parameters were evaluated in their female offspring: follicular development, PPARG levels, adipokines (including leptin, adiponectin, and chemerin as ovarian fuel sensors), serum gonadotropins (LH and FSH), the mRNA of their ovarian receptors, and the expression of steroidogenic mediators. At 60 days of age, the prenatally hyperandrogenized (PH) female offspring displayed both an irregular ovulatory phenotype and an anovulatory phenotype with altered follicular development and the presence of cysts. Both PH groups showed altered levels of both proteins and mRNA of PPARG and a different expression pattern of the adipokines studied. Although serum gonadotropins were not impaired, there were alterations in the mRNA levels of their ovarian receptors. The steroidogenic mediators Star, Cyp11a1, Cyp17a1, and Cyp19a1 were altered differently in each of the PH groups. We concluded that androgen excess during prenatal life leads to developmental programming effects that affect ovarian fuel sensors and steroidogenesis in a phenotype-specific way.

Initial ovulation rate and follicle population after injection of inhibin-neutralizing antiserum in the late-prepubertal rat

1991 ◽  
Vol 130 (2) ◽  
pp. 289-296 ◽  
Author(s):  
H. J. Sander ◽  
H. M. A. Meijs-Roelofs ◽  
E. C. M. van Leeuwen ◽  
P. Kramer ◽  
W. A. van Cappellen
Keyword(s):  
Neutralizing Antibodies ◽  
Ovulation Rate ◽  
Female Rats ◽  
Corpora Lutea ◽  
Female Rat ◽  
Follicle Growth ◽  
Immune Control ◽  
Immature Female ◽  
Antral Follicles ◽  
Control Serum

ABSTRACT In late-prepubertal female rats passive immunoneutralization of endogenous inhibin was achieved by injection of inhibin antiserum. Effects on follicle population, timing of sexual maturation, ovulation rate at first and second oestrus and serum FSH levels were studied. Rats were injected with antiserum, (non-immune) control serum from castrated sheep (castrated serum) or their IgG fractions, or with saline on day 33 or 3 or 2 days (days −3/−2) before the expected day of first ovulation, day 38·5±0·2 (n = 70). Blood was collected from different subgroups at 8, 24 and 48 h, and at first and second oestrus after injection. At necropsy, ovaries were histologically prepared for differential counting of follicles (48 h and first oestrus) and counting of corpora lutea (CL; first and second oestrus) as an index of ovulation rate. Results from rats injected with either serum or its IgG fraction were not different, as was the case when rats were injected with either castrated serum or saline. Thus, results from groups treated with antiserum and antiserum IgG were combined and labelled 'antiserum', and the castrated serum, castrated serum IgG and saline-treated groups were combined and labelled 'control'. The activity of inhibin-neutralizing antibodies in the circulation of antiserum-treated rats was reduced by 43% between 8 h and second oestrus after injection, as determined by the binding of purified bioactive radioiodinated 31 kDa bovine inhibin. After antiserum injection on day 33, more healthy antral follicles (vol. > 100 × 105 μm3, diameter > 260 μm) were present in the ovaries at 48 h (70·6 vs 54·4; P < 0·05) and at first oestrus (73·1 vs 50·8; P < 0·05) if first oestrus was reached within 5 days, but numbers were not different if first oestrus was more than 5 days after injection (52·6 vs 50·8). The number of CL after injection of antiserum on day 33 was increased at first oestrus compared with control (13·4±0·5, n = 30, vs 10·0±0·2, n = 40; P<0·001), an effect that was even more clearly present in antiserum-injected rats ovulating within 5 days (14·4±0·7, n = 20; P < 0·001). Rats injected with antiserum at days −3/−2 showed a doubling of ovulation rate at first oestrus when compared with control animals (21·5±0·8, n = 12, vs 10·5±0·2, n = 15; P < 0·001). No differences in the number of CL was seen at second oestrus. Age and body weight on the day of first ovulation were not influenced by antiserum treatment. Serum FSH was significantly (P < 0·01) increased at 8 h after antiserum injection on either day 33 or on days −3/−2 to a level of 250 and 800% of control levels respectively. Thus, injection with inhibin–neutralizing antiserum into prepubertal female rats resulted, through an increase in serum FSH concentration 8 h after injection, in the growth of additional numbers of healthy antral follicles. Supranormal ovulation rate occurred if antiserum injections were given within the last 5 days before first ovulation, with a maximal ovulation rate after injection on days −3/−2. The data support the view that, in the immature female rat during the last 5 days before the day of first ovulation, inhibin is (through its regulation of serum FSH levels) progressively involved in the control of follicle growth and ovulation rate. Journal of Endocrinology (1991) 130, 289–296

scholarly journals Profiling of superoxide dismutase isoenzymes in compartments of the developing bovine antral follicles

Reproduction ◽  
2010 ◽  
Vol 139 (5) ◽  
pp. 871-881 ◽  
Author(s):  
Catherine M H Combelles ◽  
Emily A Holick ◽  
Louis J Paolella ◽  
David C Walker ◽  
Qiaqia Wu
Keyword(s):  
Superoxide Dismutase ◽  
Granulosa Cells ◽  
Follicular Fluid ◽  
Follicular Development ◽  
Cumulus Cells ◽  
Antral Follicle ◽  
Supporting Evidence ◽  
Sod Activity ◽  
Antral Follicles ◽  
Sod Isoforms

The antral follicle constitutes a complex and regulated ovarian microenvironment that influences oocyte quality. Oxidative stress is a cellular state that may play a role during folliculogenesis and oogenesis, although direct supporting evidence is currently lacking. We thus evaluated the expression of the three isoforms (SOD1, SOD2, and SOD3) of the enzymatic antioxidant superoxide dismutase in all the cellular (granulosa cells, cumulus cells, and oocytes) and extracellular (follicular fluid) compartments of the follicle. Comparisons were made in bovine ovaries across progressive stages of antral follicular development. Follicular fluid possessed increased amounts of SOD1, SOD2, and SOD3 in small antral follicles when compared with large antral follicles; concomitantly, total SOD activity was highest in follicular fluids from smaller diameter follicles. SOD1, SOD2, and SOD3 proteins were expressed in granulosa cells without any fluctuations in follicle sizes. All three SOD isoforms were present, but were distributed differently in oocytes from small, medium, or large antral follicles. Cumulus cells expressed high levels of SOD3, some SOD2, but no detectable SOD1. Our studies provide a temporal and spatial expression profile of the three SOD isoforms in the different compartments of the developing bovine antral follicles. These results lay the ground for future investigations into the potential regulation and roles of antioxidants during folliculogenesis and oogenesis.

scholarly journals Assessment of current methods of laboratory diagnosis of bacterial vaginosis

2014 ◽  
Vol 63 (1) ◽  
pp. 26-32
Author(s):  
Kira Valentinovna Shalepo ◽  
Veronika Victorovna Nazarova ◽  
Yulia Nicolaevna Menukhova ◽  
Tatiana Andreevna Rumyantseva ◽  
Alexander Evgenievich Guschin ◽  
...  
Keyword(s):  
Polycystic Ovary ◽  
Free Testosterone ◽  
Antral Follicle ◽  
Laboratory Diagnosis ◽  
Reproductive Age ◽  
Blood Levels ◽  
Aromatase Activity ◽  
Women Of Reproductive Age ◽  
Ovary Syndrome ◽  
Antral Follicles

41 women with polycystic ovary syndrome (PCOS) and 15 healthy women of reproductive age were examined to evaluate ovarian aromatase activity. Aromatase activity was determined by the decrease of estradiol level after peroral intake of aromatase inhibitor letrosol. To examine aromatase activity of antral follicle (∆E2) was divided on the blood level of antimullerian hormone (AMH), which is corresponded to the number of antral follicles. Significant variations of aromatase activity of antral follicles in patients with PCOS were determined: in 34.1 % of women it was within physiological ranges, in 48.8 % of women it was decreased and in 17.1 % of women it was increased. Aromatase activity of antral follicles in patients with PCOS correlated with blood levels of estradiol (r = 0.67), estron (r = 0.27), free testosterone(r = 0.43), androstendion (r = 0.34) and body mass index (r = 0.30). Aromatase activity had reverse correlation with number of antral follicles. Athors suggest that the sensitivity of the ovaries to gonadotropinic stimulation is decreased in patients with PCOS and low aromatase activity.

scholarly journals Evaluation of Anti-Mullerian Hormone Predictive Value and Antral Follicle Count in the Success Rate of Ovarian Drilling in Polycystic Ovary Syndrome

2020 ◽  
Vol 21 (6) ◽  
Author(s):  
Leili Hafizi ◽  
Akram Behrouznia ◽  
Maliheh Amirian ◽  
Mina Baradaran ◽  
Seyedeh Azam Pourhoseini
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Clomiphene Citrate ◽  
Antral Follicle ◽  
Serum Levels ◽  
Antral Follicle Count ◽  
Ovary Syndrome ◽  
Antral Follicles ◽  
Laparoscopic Ovarian Drilling ◽  
Ovarian Drilling

Background: Laparoscopic ovarian drilling (LOD) is recommended for the treatment of women with polycystic ovary syndrome (PCOS) resistant to clomiphene citrate. Objectives: This study aimed to evaluate the effect of ovarian drilling on the serum levels of anti-mullerian hormone (AMH), androgens, and the number of antral follicles. Methods: This was a pre- and post-clinical trial performed on 30 infertile women with PCOS resistant to clomiphene citrate. Patients underwent standard laparoscopic ovarian drilling. Serum levels of AMH and androgens and antral follicle count (AFC) were surveyed before LOD and three and six months after LOD. The ovarian ovulation rate in each month was also monitored for six months. Then, the association between changes in these parameters, especially the level of AMH, and postoperative ovulation was investigated. A P < 0.05 was considered statistically significant. Results: The number of antral follicles three (3.00 ± 8.00) and six months (7.73 ± 4.14) after ovarian drilling showed a significant decrease compared to preoperative values (12.40 ± 4.02) (repeated-measures ANOVA, P < 0.001). The mean AMH (6.78 ± 1.08 versus 12.25 ± 1.35; P = 0.005) and the antral follicle count (7.71 ± 0.54 versus 12.29 ± 0.67 and P < 0.001) were lower in ovulation than in non-ovulation patients. The significantly more AMH reductions were seen in pregnant women (3.63 ± 5.61) than in non-pregnant women (3.63 ± 1.24) (P = 0.01). Conclusions: It may be possible to use the changes in AMH and AFC to predict the success rate of LOD.

Regulation by 3,5,3ʹ-tri-iodothyronine and FSH of cytochrome P450 family 19 (CYP19) expression in mouse granulosa cells

2018 ◽  
Vol 30 (9) ◽  
pp. 1225 ◽  
Author(s):  
Juan Liu ◽  
Yingying Han ◽  
Ye Tian ◽  
Xuechun Weng ◽  
Xusong Hu ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Granulosa Cell ◽  
Granulosa Cells ◽  
Follicular Development ◽  
Sterol Biosynthesis ◽  
Akt Pathway ◽  
Preantral Follicle ◽  
Follicle Growth ◽  
Cytochrome P450 Family ◽  
Cyp19 Expression

Cytochrome P450 family 19 (CYP19) plays an important role in follicular development, which is regulated by FSH. Although 3,5,3′-tri-iodothyronine (T3) combines with FSH to induce preantral follicle growth and granulosa cell development, the mechanism involved remains unclear. The aim of the present study was to determine the cellular and molecular mechanisms by which thyroid hormone (TH) and FSH regulate CYP19 expression and sterol biosynthesis during preantral follicle growth. Mice were injected subcutaneously (s.c.) with eCG (Equine chorionic gonadotropin). The results showed that eCG increased CYP19 expression in ovarian cells. CYP19 expression in granulosa cells was increased after FSH treatment, and this response was enhanced by T3. Knockdown of CYP19 significantly decreased granulosa cell viability and hormone-stimulated proliferation. In addition, CYP19 knockdown also blocked T3- and FSH-induced oestradiol (E2) synthesis in granulosa cells. Furthermore, activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway was required for T3 and FSH regulation of CYP19 expression. In conclusion, the results of the present study indicate that CYP19 is important for T3- and FSH-induced granulosa cell development in the early stages. CYP19 could be a downstream effector of the PI3K/Akt pathway in regulating TH and FSH during follicular development and sterol biosynthesis. The findings suggest that CYP19 is a novel mediator of T3- and FSH-induced follicular development.

scholarly journals Ovarian aromatase activity in polycystic ovarian syndrome

2014 ◽  
Vol 63 (1) ◽  
pp. 10-16 ◽  
Author(s):  
Igor Pavlovich Nikolayenkov ◽  
Vladimir Vsevolodovich Potin ◽  
Marina Anatolyevna Tarasova ◽  
Natalya Nikolayevna Tkachenko ◽  
Maria Igorevna Yarmolinskaya ◽  
...  
Keyword(s):  
Polycystic Ovarian Syndrome ◽  
Polycystic Ovary ◽  
Free Testosterone ◽  
Antral Follicle ◽  
Reproductive Age ◽  
Blood Levels ◽  
Aromatase Activity ◽  
Ovary Syndrome ◽  
Antral Follicles ◽  
Ovarian Syndrome

41 women with polycystic ovary syndrome (PCOS) and 15 healthy women of reproductive age were examined to evaluate ovarian aromatase activity. Aromatase activity was determined by the decrease of estradiol level after peroral intake of aromatase inhibitor letrosol. To examine aromatase activity of antral follicle (∆E2) was divided on the blood level of antimullerian hormone (AMH), which is corresponded to the number of antral follicles. Significant variations of aromatase activity of antral follicles in patients with PCOS were determined: in 34.1 % of women it was within physiological ranges, in 48.8 % of women it was decreased and in 17.1 % of women it was increased. Aromatase activity of antral follicles in patients with PCOS correlated with blood levels of estradiol (r = 0.67), estron (r = 0.27), free testosterone(r = 0.43), androstendion (r = 0.34) and body mass index (r = 0.30). Aromatase activity had reverse correlation with number of antral follicles. Athors suggest that the sensitivity of the ovaries to gonadotropinic stimulation is decreased in patients with PCOS and low aromatase activity.

scholarly journals Correlation between Anti-Mullerian Hormone Levels and Antral Follicle Numbers in Polycystic Ovary and Metabolic Syndromes

2020 ◽  
Author(s):  
Huo Fu ◽  
Youshi Lin ◽  
Xueqing Deng ◽  
Lin Wu
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Fasting Blood Glucose ◽  
Density Lipoprotein ◽  
Fold Increase ◽  
Antral Follicle ◽  
Serum Levels ◽  
Reproductive Technologies ◽  
Ovary Syndrome ◽  
Antral Follicles

Abstract Background Anti-Mullerian hormone (AMH) is expressed by granulosa cells of the pre-antral and small antral follicles in the ovary. Serum AMH levels are significantly higher in women with polycystic ovary syndrome (PCOS) due to an increased number of antral follicles and also a higher production per antral follicle. We proposed diagnostic criteria for the identification of PCOS that are based on variation in the AMH concentrations.Methods This study explored the relationship between serum AMH levels and other hormonal markers in patients with polycystic ovary syndrome (PCOS) and metabolic syndrome. One hundred fifty patients with PCOS and normally cycling women were examined in a cohort study. Of these, some were candidates for the assisted reproductive methods. The following serum levels were measured in all patients on day 5 of the menstrual cycle: AMH, glucose, HOMA/IP, BMI, testosterone and cholesterol, lipoproteins and triglycerides.Results In the PCOS group, a 2-fold increase in the serum AMH level was observed as compared to the controls. With AMH, the following increments were seen: testosterone (by 184%); fasting blood glucose (by 18%); fasting insulin (83.86%); HOMA/IR (by 64.23%); mean cholesterol (by 30%); mean triglycerides (by 17%); and BMI (by 26.75%). The high-density lipoprotein concentration decreased by 29.3%.Conclusion Thus, monitoring the level of AMH allows predicting for OHSS during the ovulation induction and during the use of assistive reproductive technologies. Such a practice also allows deciding on the treatment strategy for obesity, hirsutism, type II diabetes, infertility and cardiovascular diseases.

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