Aberrant expression of growth differentiation factor-9 in oocytes of women with polycystic ovary syndrome.
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.
Teixeira Filho
Fabio Lopes
FL
Universidade Federal de São Paulo, São Paulo, Brazil 01311-940.
Baracat
Edmund Chada
EC
Lee
Taek Hoo
TH
Suh
Chang Suk
CS
Matsui
Motozumi
M
Chang
R Jeffrey
RJ
Shimasaki
Shunichi
S
Erickson
Gregory F
GF
D000328:Adult; D055430:Bone Morphogenetic Protein 15; D021983:Cyclophilins / Q000235:genetics; D005260:Female; D055429:Growth Differentiation Factor 9; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D008875:Middle Aged; D009865:Oocytes / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values
C525901:BMP15 protein, human; D055430:Bone Morphogenetic Protein 15; C525897:GDF9 protein, human; D055429:Growth Differentiation Factor 9; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D021983:Cyclophilins