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

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.

The Effect of Green Tea on IL-6 and CRP level in Model of Polycystic Ovary Syndrome as an Inflammation State

“…Interleukin-6 is on 7p21 chromosome. International Journal of Cellular & Molecular Biotechnology 2014 (2014 [1][2][3][4][5][6][7][8][9][10][11][12] Available online at www.ispacs.com/ijcmb is basically regulated by Beta Kappa core factor (NK-kb) and interleukin IL-6 causes stimulus, regulates synthesis of acute phase protein, activates axis of hypothalamus -pituitary and disorder in signal transduction of glucose through changing activity of serine -threonine kinases. Interleukin-6 plays a key role in the pathogenesis of chronic inflammation, insulin resistance, and CV diseases [2].…”

The bioactivity of human bone morphogenetic protein-15 is sensitive to C-terminal modification: Characterization of the purified untagged processed mature region

“…Mutations in these genes lead to reproductive defects in animals and with the recombinant forms of these growth factors the actions of the oocyte can be mimicked (Gilchrist et al 2004b). Further, mutations in the human BMP15 or GDF9 genes are associated with polycystic ovary syndrome Page 2 of 27 A c c e p t e d M a n u s c r i p t 2 (PCOS), premature ovarian failure (POF) or dizygotic twinning (Teixeira Filho et al 2002;Di Pasquale et al 2004;Dixit et al 2005;Di Pasquale et al 2006;Dixit et al 2006;Laissue et al 2006;Palmer et al 2006). Furthermore, both proteins have been shown to regulate ovulation rate in sheep (Galloway et al 2000;Juengel et al 2004).…”

Characterization of recombinant human growth differentiation factor-9 signaling in ovarian granulosa cells

“…Mutations in the hGDF9 gene are associated with various reproductive abnormalities. It has been shown that aberrant expression of GDF9 is associated with polycystic ovary syndrome (PCOS) (Teixeira Filho et al 2002) and screening of women with premature ovarian failure (POF) has revealed mutations in the GDF9 gene (Dixit et al 2005;Laissue et al 2006). In 2004 a rare deletion mutation in the hGDF9 gene was described in heterozygous sisters with spontaneous dizygotic twins (Montgomery et al 2004) and more recently new variants in the hGDF9 gene that are significantly more common in mothers of dizygotic (DZ) twins than controls were described, suggesting that rare GDF9 variants contribute to the likelihood of DZ twinning (Palmer et al 2006).…”