Serum GDF9 and BMP15 as Markers of Ovarian Function in Healthy Women and Women with Polycystic Ovary Syndrome

Abstract

Background: The oocyte-secreted factors growth differentiation factor-9 (GDF9) and bone morphogenetic protein-15 (BMP15) are key regulators of female fertility and are predominantly expressed by oocytes. Recently, methods to quantitate these proteins in serum have demonstrated diagnostic potential. It is unknown if concentrations reflect ovarian and endocrine function, particularly in women with polycystic ovary syndrome (PCOS), where GDF9/BMP15 function is suggested to be aberrant. Aim: To determine if serum GDF9/BMP15 are associated with ovarian and endocrine parameters, and the ovarian pathologies, PCOM and PCOS. Method: Women aged 21-45 years (n=381) were from a cross-sectional study at the National University Hospital, Singapore, including healthy volunteers and referrals from gynecological clinics. Transvaginal ultrasound scans, blood tests and questionnaire were performed. Serum GDF9 and BMP15 were assessed relative to ovarian (cycle regularity, ovarian volume, AFC, AMH) and androgenic (testosterone, DHT, androstenedione, DHEAS, SHBG, mFG score) characteristics. PCOM and PCOS were determined using the Rotterdam criteria. Statistical analyses used parametric survival models and Kendall’s tau correlation appropriate for data containing values below the limit of detection. Results: Serum GDF9 and BMP15 were detectable in 40% and 41% of women, respectively. Serum GDF9 positively correlated with ovarian volume (p=0.02), AFC (p=0.004), and weakly with AMH (p=0.05). Furthermore, irregular menstrual cycles were associated with high GDF9 (p=0.005), and similar, although non-significant associations were seen for BMP15. When stratified into PCOS (n=130), PCOM (n=59), and control (n=192), GDF9 and BMP15 concentrations were not significantly different, and were not associated with the majority of androgenic features of PCOS. However, the relationship between GDF9 and AFC was significantly different between PCOM, PCOS and control women (p=0.02). Conclusion: These results suggest that serum GDF9 and BMP15 reflect ovarian characteristics but not androgenic characteristics of PCOS, and that the relationships between GDF9 and AFC may be aberrant in women with PCOM/PCOS.