Alterations of folliculogenesis in women with polycystic ovary syndrome (original) (raw)

Endocrinology: Iminunohistochemical study of steroidogenesis and cell proliferation in polycystic ovarian syndrome

Human Reproduction, 1996

We evaluated the immunolocalization of the steroidogenic enzymes involved in the production of ovarian steroids, including the cholesterol side-chain cleavage enzyme (P450scc), 3p"-hydroxysteroid dehydrogenase (HSD), 17ahydroxylase (P450cl7) and aromatase (P450arom), oestrogen receptor (ER) and androgen receptor (AR), a steroidogenic transcription factor, Ad4-binding protein (Ad4BP) and a cell cycle-related nuclear antigen, Ki67, in five patients with polycystic ovarian syndrome (PCOS). Results were compared with those from normal cycling human ovaries to study in situ ovarian steroidogenesis and cell proliferation in polycystic ovaries (PCO). We classified the follicles morphologically according to the development of granulosa cells: type A, more than four layers (n = 7); type B, one to three layers (n = 11); and type C, theca interna cells only (n = 21). ER and P450arom were not observed in any of the follicles examined. In type A follicles, P450scc, 3P-HSD, P450cl7, AR and Ad4BP were observed in theca cells in all seven follicles examined, but the granulosa cells were positive only for Ad4BP (4/7) and AR (7/7). These immunohistolocalization patterns resembled those in non-selected antral follicles of normally cycling human ovaries. In theca cells from types B and C follicles, follicles positive for the steroidogenic enzymes, AR and Ad4BP were decreased in number. There were no significant differences between types A and B PCO follicles in the Ki67 labelling index of granulosa or theca cells, and between PCO and antral follicles from normally cycling human ovaries. Data demonstrate that the follicles of PCO are by no means atretic and are actively involved in both steroidogenesis and cell proliferation. The absence of ER and aromatase expression in the granulosa cells of PCO may be important in abnormal follicular development in patients with PCOS.

Expression of genes controlling steroid metabolism and action in granulosa-lutein cells of women with polycystic ovaries

Molecular and Cellular Endocrinology, 2019

Introduction Aberrant function of granulosa cells has been implicated in the pathophysiology of PCOS. Materials & methods GL cells were collected during oocyte retrieval for IVF/ICSI. RT-qPCR was used to compare gene expression between 12 control women, 12 with ovulatory PCO and 12 with anovulatory PCOS. To examine which genes are directly regulated by androgens, GL cells from an additional 12 control women were treated in-vitro with 10nM dihydrotestosterone (DHT). Results Women with PCOS showed reduced expression of CYP11A1 3-fold (p=0.005), HSD17B1 1.8-fold (p=0.02) and increased expression of SULT1E1 7-fold (p=0.0003). Similar results were seen in ovulatory women with PCO. GL cells treated with 10nM DHT showed a 4-fold (p=0.03) increase in expression of SULT1E1 and a 5-fold reduction in SRD5A1 (p=0.03). Conclusions These findings support the notion that aberrant regulation of steroid metabolism or action play a part in ovarian dysfunction in PCOS

Estrogen receptor α and β expression in theca and granulosa cells from women with polycystic ovary syndrome

The Journal of Clinical Endocrinology and Metabolism, 2002

A defining characteristic of dominant follicles is high estradiol concentrations. Abnormal expression of estrogen receptors (ERs) could contribute to poor follicular development and ovulatory failure in polycystic ovary syndrome (PCOS). The aim of this study was to determine whether there are differences in ER␣ and ER␤ expression in granulosa cells (GC) and theca cells (TC) from women with PCOS, compared with regularly cycling women. GC and TC were obtained by microdissection from 12 polycystic and 23 normal ovaries. ER␣ and ER␤ mRNA and protein expression were measured by semiquantitative RT-PCR and Western blot, respectively. In control ovaries, both GC and TC ER␣ mRNAs were higher in small antral (SA) than in dominant follicles. ER␣ mRNA was similar in PCOS and size-matched control follicles. In control follicles, ER␣ protein concentrations were higher in GC than in TC. In GC, the ER␣ concentrations were comparable among SA, dominant, and PCOS follicles. In TC, ER␣ concentrations were lower in dominant follicles but were markedly increased in PCOS. In control ovaries, GC and TC expression of ER␤ mRNA was higher in SA, compared with dominant follicles. In PCOS, ER␤ mRNA was intermediate between SA and dominant follicles in both GC and TC. In GC, the ER␤ protein concentrations followed the same pattern as mRNA expression; but in TC ER␤, protein in PCOS was equivalent to that in dominant follicles. The results of this study demonstrate that there are significant alterations in the expression of ER␣ and ER␤ in PCOS that may be related to abnormal follicular development. (J Clin Endocrinol Metab 87: 5532-5538, 2002)

Significance of pro-angiogenic estrogen metabolites in normal follicular development and follicular growth arrest in polycystic ovary syndrome

Human Reproduction, 2020

STUDY QUESTION Do alterations in pro- and anti-angiogenic estrogen metabolites in follicular fluid (FF) contribute to the follicular growth arrest and anovulation associated with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER FF of PCOS women with anovulation have reduced levels of pro-angiogenic estrogen metabolites (EMs) and vascular endothelial growth factor (VEGF) compared to that of fertile women with regular menstrual cycles, but exogenous gonadotropins increase the pro-angiogenic EMs and VEGF levels in PCOS women. WHAT IS KNOWN ALREADY PCOS is characterized by the arrest of follicular development that leads to chronic anovulation. Follicular arrest is generally associated with elevated plasma levels of luteinizing hormone (LH), androgens and anti-Mullerian hormone (AMH). There is also reduced angiogenesis in the follicles of PCOS women compared to those of normal cycling women. It is known that angiogenesis is a critical factor during follicular development. We and other in...

Dysregulation of the Anti-Müllerian Hormone System by Steroids in Women With Polycystic Ovary Syndrome

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.

Aromatase mRNA expression in individual follicles from polycystic ovaries

Molecular Human Reproduction, 1998

Polycystic ovary syndrome (PCOS) is a common reproductive disorder characterized by arrested follicular development prior to selection of a dominant follicle. Dominant follicles produce large amounts of oestradiol but PCOS follicles do not. With several potential aromatase (P450 AROM ) inhibitors in follicular fluid, the question arises whether P450 AROM is expressed in PCOS granulosa cells, but the activity is inhibited, or whether P450 AROM is not expressed in PCOS. The purpose of the present study was to determine whether P450 AROM mRNA expression is altered in PCOS and to correlate P450 AROM mRNA expression in individual follicles with aromatase stimulatory bioactivity and oestradiol in the follicular microenvironments. P450 AROM mRNA was measured in individual follicles from 16 PCOS and 48 regularly cycling control women by quantitative polymerase chain reaction (PCR) and correlated with follicular fluid oestradiol concentrations and aromatase stimulating bioactivity measured by the rat granulosa cells aromatase bioassay. Follicular fluid oestradiol was low in all control follicles <7 mm in diameter. Some follicles ജ7 mm contained elevated oestradiol values (P < 0.01) and all had an androstenedione:oestradiol ratio of Ͻ4. Only in granulosa cells from follicles ജ7 mm with an androstenedione:oestradiol ratio of <4 were P450 AROM mRNA levels increased (P < 0.05). These same follicles also contained increased levels of aromatase stimulating bioactivity whereas follicles <7 mm or with androstenedione:oestradiol ratio of >4 contained little or no bioactivity. All PCOS follicles contained low levels of oestradiol , P450 AROM mRNA and aromatase stimulating bioactivity similar to size-matched control follicles. These data indicate that P450 AROM mRNA expression and oestradiol production begin in developing follicles when they reach~7 mm in diameter. Oestradiol production is low in PCOS follicles because there is insufficient aromatase stimulating bioactivity to increase P450 AROM mRNA expression.

Immunohistochemical study of steroidogenesis and cell proliferation in polycystic ovarian syndrome

Human reproduction (Oxford, England), 1996

Alterations of folliculogenesis in women with polycystic ovary syndrome (original) (raw)

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