Chenodeoxycholic acid improves oocyte maturation and embryo quality during bisphenol A exposure by activating the EGFR-ERK1/2 signaling pathway

Abstract

Chenodeoxycholic acid (CDCA) is a free bile acid present in the follicular fluid surrounding growing oocytes. In this study, we demonstrate that supplementation with CDCA activates the EGFR signaling in cumulus-oocyte complexes (COCs) to improve oocyte quality. Bisphenol A (BPA), a well-documented environmental toxicant, disrupts female reproductive function. We found that BPA exposure suppressed EGFR signaling in porcine COCs, leading to meiotic arrest, increased the concentration of cGMP and cAMP. However, supplementation with CDCA improves oocyte maturation and embryo quality during BPA exposure. Cumulus cells, as essential support cells for oocytes, regulate oocyte meiotic resumption and maturation mainly by providing signaling molecules and energy. Notably, CDCA treatment of germinal vesicle (GV) stage denuded oocytes (DOs) did not significantly affect the oocyte maturation rate. These findings indicate that the influence of CDCA on oocyte development may be mediated via its action on the surrounding cumulus cells. In addition, we knocked down EGFR expression in cumulus cells using siRNA and co-cultured them with DOs. These findings revealed that when EGFR expression in cumulus cells was suppressed, the beneficial effects of CDCA were effectively attenuated. These findings demonstrate that CDCA affects oocyte quality by activating the EGFR signaling in cumulus cells. In summary, the present study reveals that CDCA promotes oocyte meiotic recovery and improves oocyte quality by activating EGFR signaling in cumulus cells, thereby enhancing the developmental potential of embryos.

Keywords

• CDCA
• BPA
• EGFR
• cGMP
• cAMP
• Mitochondrial