Age-related decline in the expression of GDF9 and BMP15 genes in follicle fluid and granulosa cells derived 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 two have been found among patients with poor ovarian response (POR). In this prospective cohort study, we have determined the expression of the GDF9 and BMP15 genes in follicle fluid (FF) and granulosa cells (GCs) derived 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 by the Bologna criteria and sub-divided into 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 the GDF9 and BMP15 genes 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 two pronuclei (2PN) oocytes and transplantable embryos, in addition with higher rates of implantation and clinical pregnancy (P < 0.05). The expression level of GDF9 and BMP15 genes in the FF and GCs differed significantly among the three groups (P < 0.05), showing a trend of decline along with age. Conclusions: For poor ovarian responders, in particular those over 40, the expression of GDF9 and BMP15 is declined with increased age and in accompany with poorer oocyte quality and IVF outcome.

Comprehensive analysis of miRNA–mRNA interactions in ovaries of aged mice

“…The expression of growth differentiation factor 9 ( Gdf9 ) and bone morphogenetic protein 15 ( Bmp15 ) can serve as a predictor of ovarian aging. Age‐related decline in the expression of these two genes is associated with poor ovarian response to ovarian hyperstimulation, resulting in poor oocyte quantity and quality (Gong et al, 2021). Interestingly, our analyses revealed that Bmp 15 harbors two binding sites for miR‐200b‐3p and one for miR‐741‐3p.…”

Periplaneta americana peptide decreases apoptosis of pig‐ovary granulosa cells induced by H2O2 through FoxO1

“…As the important components of follicles, granulosa cells exist in follicular fluid and are closely related to follicular growth (Gong et al., 2021). Oxidative stress can cause the apoptosis of granulosa cells (Shen et al., 2017).…”