Downregulation of gap junctional intercellular communication and connexin 43 expression by bisphenol A in human granulosa cells

Gap junctional intercellular communication (GJIC) is the transfer of ions, metabolites, and second messengers between neighboring cells through intercellular junctions. Connexin 43 (Cx43) was found to be the type of gap junction protein responsible for human granulosa cells (GCs) and oocyte communication, which is required for folliculogenesis and oocyte maturation. Bisphenol A (BPA), an estrogenic-like endocrine-disrupting chemical, is one of the most widely produced chemicals around the world. There are reports that the chemical might cause endometrial tumorigenesis and several female reproductive disorders. This study demonstrated that cell culture medium, containing antioxidants (N-acetyl-l-cysteine and l-ascorbic acid-2-phosphate), was able to enhance the survival and self-renewal of GCs. In addition, we found that BPA at environmentally relevant concentration (10−7 M) reduced Cx43 expression and GJIC in GCs through estrogen receptor and mitogen-activated protein kinase pathways. The results of this study not only reveal the reproductive toxicity of BPA but also provide possible mechanisms by which BPA inhibited GJIC in GCs.