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Anti-Mullerian Hormone, Its Receptor, FSH Receptor, and Androgen Receptor Genes Are Overexpressed by Granulosa Cells from Stimulated Follicles in Women with Polycystic Ovary Syndrome

Department of Endocrine Gynaecology and Reproductive Medicine (S.C.-J., D.D.), Hôpital Jeanne de Flandre, Centre Hospitalier Régional Universitaire, and Faculty of Medicine of Lille, Université de Lille II, 59037 Lille, France; Institut National de la Santé et de la Recherche Médicale, Unit 782 (S.P.J., A.L., J.G., N.d.C.), Clamart F-92140, France; and University of Paris-Sud, Unit Mixed of Research S0782 (S.P.J., A.L., J.G., N.d.C.), Clamart F-92140, France

Address all correspondence and requests for reprints to: Dewailly Didier, Department of Endocrine Gynaecology and Reproductive Medicine, Hôpital Jeanne de Flandre, C.H.R.U., 59037 Lille, France. E-mail: ddewailly{at}chru-lille.fr.

Context: In the polycystic ovary syndrome (PCOS), in addition to intrinsic thecal dysregulation leading to hyperandrogenism, a granulosa cell (GC) dysregulation may occur. Expression of anti-Müllerian hormone (AMH), FSH receptor (FSHR) and androgen receptor (AR) are suspected to be altered in PCOS GCs.

Design: The aim of this prospective study was to analyze the expression of these genes at the last stages of follicular maturation in GCs from 17 patients with PCOS and 15 controls undergoing controlled ovarian hyperstimulation during a cycle with in vitro fertilization.

Materials and Methods: On the day of oocyte retrieval, follicular fluids were collected from small follicles (SF; 8–13 mm) and large follicles (17–22 mm) in separate tubes. Total RNAs and proteins were extracted from GCs. Reverse transcription was performed and quantification of gene expression levels was achieved by real-time quantitative PCR.

Results: AMH and FSHR mRNA levels were significantly higher in PCOS than in controls in GCs from both SF and large follicles. Likewise, AR and AMH receptor II mRNA levels in GCs from SF were significantly higher in PCOS compared with controls. In both PCOS patients and controls, AMH and AR mRNA levels correlated strongly, positively, and independently to FSHR mRNA levels.

Conclusion: Using quantitative RT-PCR, AMH, AMH receptor II, FSHR, and AR genes were shown to be overexpressed by GCs from stimulated follicles of women with PCOS undergoing controlled ovarian hyperstimulation. This could be the sign of a maturation defect or may reflect hyperandrogenism.

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