Age-Related Decrease of Expression of GDF9 and BMP15 Genes in Follicle Fluid and Granulosa Cells from Poor Ovarian Responders

Abstract

Background: Growth differentiation factor 9 ( GDF9 ) and bone morphogenetic protein 15 ( BMP15 ) genes play important roles in folliculogenesis. Altered expression of the GDF9 and BMP15 genes have been found among patients with poor ovarian response (POR). In this prospective cohort study, we determined the expression of the GDF9 and BMP15 genes in follicle fluid (FF) and granulosa cells (GCs) from poor ovarian responders grouped by age, and explored its correlation with the outcome of in vitro fertilization and embryo transfer (IVF-ET) treatment. Methods: A total of 196 patients with POR were enrolled from a tertiary teaching hospital. The patients were diagnosed based on the Bologna criteria and sub-divided into different age groups: group A (< 35 year old), group B (35 ~ 40 year old) and group C (> 40 year old). A GnRH antagonist protocol was conducted for all patients, and FF and GCs were collected after oocyte retrieval. Expression of GDF9 and BMP15 in the FF and GCs was determined with enzyme linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting. Results: Compared with group C, groups A and B had significantly more transplantable embryos and higher rates of implantation and clinical pregnancy ( P < 0.05). Group A also had significantly more two pronuclei (2PN) oocytes ( P < 0.05). The expression level of GDF9 and BMP15 in the FF and GCs differed significantly among the three groups ( P < 0.05), showing a trend of decline with age. Conclusion: For poor ovarian responders, the expression of GDF9 and BMP15 is declined with increased age in accompany with poorer oocyte quality and IVF outcome, particularly for those over 40.