Effects of growth differentiation factor-9 and bone morphogenetic protein-15 on the apoptosis of cumulus cells in patients with polycystic ovary syndrome

Lei Wang ,Dianliang Lin ,Yuefan Kang ,Yuan Lin ,Baodong Zheng ,Sun Yan ,Shengrong Du

doi:10.3760/cma.j.issn.2096-2916.2017.10.002

Abstract

Objective To investigate the effects of abnormal expression of growth differentiation factor-9(GDF-9) and bone morphogenetic protein-15 (BMP-15) on the apoptosis of cumulus cells in patients with polycystic ovary syndrome (PCOS) undergoing controlled ovarian hyperstimulation (COH). Methods Cumulus cells were collected from PCOS patients (n=30) and control group (n=60) who underwent intracytoplasmic sperm injection (ICSI) in our hospital. Cumulus cells were collected and purified after oocyte retrieval. The apoptosis of cumulus cells was tested by terminal deoxynucleotidyl transferase-mediated dUTP nick-End labeling (TUNEL) and flow cytometry. Immunocytochemistry was used to detect the expression of GDF-9, BMP-15 protein in cumulus cells and Motic Med 6.0 system was used to analyze average optical density of cumulus cells. The mRNA levels of GDF-9, BMP-15, B-cell lymphoma-2 (BCL-2) and Bcl-2 associated X (BAX) in cumulus cells were analyzed by real-time PCR. Results The number of punctured follicles, retrieved oocytes in PCOS group were higher than those in control group. The apoptosis rate of cumulus cells in PCOS group was higher than that in control group. GDF-9 and BMP-15 proteins were positively stained in cytoplasm of cumulus cell in both groups. GDF-9, BMP-15, BCL-2 and BAX mRNA levels in PCOS group were significantly lower, while BAX/BCL-2 ratio was significantly higher than that in control group. According to Pearson linear correlation, GDF-9 and BMP-15 mRNA levels were significantly positively correlated with BCL-2 mRNA level, and negatively correlated with BAX mRNA in PCOS patients. Conclusion The abnormal expression levels of GDF-9 and BMP-15 in cumulus cell of PCOS patients may be one of the reasons that lead to higher cells apoptosis. Key words: Growth differentiation factor-9 (GDF-9); Bone morphogenetic protein-15 (BMP-15); Cumulus cell; Apotosis; Polycystic ovary syndrome (PCOS); Controlled ovarian hyperstimulation (COH)

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