Gene Expression in Granulosa Cells From Small Antral Follicles From Women With or Without Polycystic Ovaries (original) (raw)
Related papers
The Journal of Clinical Endocrinology & Metabolism, 2005
Context: Polycystic ovary syndrome, the most common cause of anovulatory infertility, is characterized by disordered folliculogenesis, notably increased progression from the primordial to the primary stages. This ovarian phenotype is similar to that observed in mice lacking anti-mü llerian hormone (AMH). Objective: The objective of this study is to investigate whether AMH is involved in accelerating the transition of follicles from primordial to primary stages in polycystic ovaries. Design: This study compares AMH expression in archive tissue from normal and polycystic ovaries. Setting: This is a laboratory-based study. Patients: Ovarian tissue from seven normoovulatory women and 16 women with polycystic ovaries (five of whom were anovulatory) was used in this study. Ovaries were classified by histology and with reference to menstrual cycle history and ultrasound. Main Outcome Measure: Presence and intensity of AMH expression in 1403 follicles was the main outcome measure. Results: AMH was observed from the primordial stage onward. AMH immunostaining was observed in significantly fewer primordial (P ϭ 0.007) and transitional follicles (P ϭ 0.001) in ovaries from anovulatory women with polycystic ovaries compared with women with regular cycles and either normal or polycystic ovaries. AMH-negative follicles had fewer pregranulosa cells in the largest cross-section of the follicle at both the primordial (median, four and six for AMH-negative and-positive follicles, respectively; P Ͻ 0.0001) and transitional stages (median six and nine; P Ͻ 0.0007) in normal tissue, and fewer at the transitional stage (median, seven and 11; P Ͻ 0.0001) in tissue from anovulatory women with polycystic ovaries. This suggests that AMH expression is associated with granulosa cell mitosis. Conclusions: These findings indicate a relative deficiency of AMH in primordial and transitional follicles in ovaries from anovulatory women with polycystic ovaries. This may contribute to disordered early follicle development in polycystic ovary syndrome.
Fertility and Sterility, 2011
Objective: To determine that anti-M€ ullerian hormone (AMH) has been shown to inhibits E 2 production in rodents and in luteinized granulosa cells (GC). We determined whether this occurs in human cells most highly expressing AMH (i.e., from small antral follicles) and whether this is an effect on aromatase promoter activity. We also investigated the effects of AMH on other factors determining FSH sensitivity. Design: Granulosa cells were exposed to AMH with and without gonadotropins for 48 hours. Setting: University laboratory. Patient(s): Not applicable. Intervention(s): None. Main Outcome Measure(s): Aromatase and FSH receptor messenger RNA expression measured using real time quantitative polymerase chain reaction (PCR). Aromatase promoter II activity measured using a luciferase assay. Estradiol, inhibin A and B, and vascular endothelial growth factor production were measured in the conditioned medium.
2010
Women with polycystic ovary syndrome (PCOS) undergoing ovulation induction appear to be extremely sensitive to gonadotropin stimulation and at increased risk for ovarian hyperstimulation syndrome. To determine granulosa cell responsiveness to recombinant human FSH (r-hFSH), doseresponse studies were conducted in 16 individual PCOS patients and 7 normal women. Each subject received an iv injection of r-hFSH at doses of 0, 37.5, 75, or 150 IU in a randomized fashion on four separate occasions. Blood samples were obtained at frequent intervals before and for 24 h after r-hFSH administration for measurement of gonadotropins and steroid hormones.
The Journal of Clinical Endocrinology & Metabolism, 2017
Context: Anti-Müllerian hormone (AMH) and AMH type II receptor (AMHR2) are overexpressed in granulosa cells (GCs) from women with polycystic ovary syndrome (PCOS), the most common cause of female infertility. Objective: The aim of the study was to compare the regulation of the AMH/AMHR2 system by 5adihydrotestosterone (5a-DHT) and estradiol (E2) in GCs from control subjects and women with PCOS. Design, Setting, Patients: Experiments were performed on follicular fluids (FF) and GCs from women undergoing in vitro fertilization. Main Outcome Measures: FF steroid levels were measured by mass spectrometry, and messenger RNA (mRNA) accumulation was quantified by reverse transcription real-time polymerase chain reaction. Results: Total testosterone (T), free T, and 5a-DHT FF levels were significantly higher (P , 0.001) in women with PCOS than in controls. However, E2 and sex hormone-binding globulin concentrations were comparable between the two groups. In GCs from control women, the AMH and AMHR2 expression were not affected by 5a-DHT treatment, whereas AMH mRNA levels were upregulated by 5a-DHT in GCs from patients with PCOS (2.3-fold, P , 0.01) overexpressing the androgen receptor (1.4-fold, P , 0.05). E2 downregulated the AMH and AMHR2 expression in GCs from control women (1.4-fold, P , 0.001 and 1.8-fold, P , 0.01, respectively) but had no effect on these genes in GCs from women with PCOS. This differential effect of E2 was associated with a higher estrogen receptor 1 expression in GCs from women with PCOS (1.9-fold, P , 0.05). Conclusions: In GCs from women with PCOS, the regulation of AMH and AMHR2 expression is altered in a way that promotes the overexpression of the AMH/AMHR2 system, and could contribute to the follicular arrest observed in these patients.