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Aberrant Expression of Growth Differentiation Factor-9 in Oocytes of Women with Polycystic Ovary Syndrome

Universidade Federal de São Paulo (F.L.T.F., E.C.B.), São Paulo, Brazil 01311-940; Kyungpook National University (T.H.L.), Taegu, Korea 700-721; Seoul National University College of Medicine (C.S.S.), Seoul, Korea 110-744; and Department of Reproductive Medicine (M.M., R.J.C., S.S., G.F.E.), University of California San Diego, La Jolla, California 92093-0674

Address all correspondence and requests for reprints to: Gregory F. Erickson, Ph.D., Department of Reproductive Medicine, University of California San Diego, 9500 Gilman Drive, 2058 CMME, La Jolla, California 92093-0674. E-mail: . gerickson{at}ucsd.edu

Abstract

Polycystic ovary syndrome (PCOS) is a major cause of female infertility. Despite substantial effort, the etiology and pathogenesis of PCOS and polycystic ovaries (PCO) in women remain unknown. Recent studies in laboratory animals have documented a link between dysfunction of two oocyte growth factors, growth differentiation factor-9 (GDF-9) and bone morphogenetic factor-15 (BMP-15), and aberrant folliculogenesis. Because aberrant follicle development is a hallmark of PCOS, we wondered whether the expression patterns of these growth factors might be disrupted in PCOS and PCO oocytes. To address this issue, we compared the pattern and level of expression of GDF-9 and BMP-15 mRNA in ovaries from normal cycling (n = 12), PCOS (n = 5), and PCO (n = 7) patients. In situ hybridization studies showed that the expression of GDF-9 and BMP-15 is restricted to the oocytes in all ovaries examined. Interestingly, a decreased level of GDF-9 signal was observed in developing PCOS and PCO oocytes, compared with normal. This difference was evident throughout folliculogenesis, beginning at recruitment initiation and continuing through the small Graafian follicle stage. By contrast, there were no qualitative or quantitative changes in the expression of BMP-15 mRNA in PCOS oocytes during folliculogenesis. There were also no significant differences between normal and PCOS and PCOs in the levels of the mRNA encoding the housekeeping gene, cyclophilin. Together, these results indicate that the expression of GDF-9 mRNA is delayed and reduced in PCOS and PCO oocytes during their growth and differentiation phase. Because oocyte-derived GDF-9 is crucial for normal folliculogenesis and female fertility, we suggest that a dysregulation of oocyte GDF-9 expression may contribute to aberrant folliculogenesis in PCOS and PCO women.

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