Are BPA effects on Connexins and key downstream microRNAs in bovine COCs correlated to miR-21 expression?

Abstract

Endocrine disrupting compounds such as bisphenol A (BPA) negatively affect oocyte maturation and embryo development, while promoting epigenetic changes in miRNAs (miRs), including that of miR-21. miR-21 is an integral miR involved in various developmental processes, such as oocyte maturation, granulosa cells function and embryo development. Connexin (Cx) gap junction proteins play an important role in the communication among granulosa cells and cumulus cells and are impacted by bisphenols and linked to specific miRs. We hypothesize that miR-21 downregulation and BPA exposure affect Cxs mRNA and downstream miRNAs expression. Oocyte maturation was unaffected by miR-21 downregulation, but was significantly decreased (p = 0.0059) following BPA exposure. Also, BPA significantly increased Cx 43 mRNA levels when miR-21 is knocked-down in cumulus cells (p = 0.0476). miR-378a, a target of Cx 43 and 37, increased due to BPA and combination treatment in denuded oocytes (p = 0.0349) and cumulus cells (p = 0.0177). miR-96, a Cx 26 target, displayed a significant decrease in all samples following BPA exposure, in a miR-21 independent manner (p < 0.05). These data strengthen previous evidence of a strict relationship among BPA, miR-21 and especially Cx 43 and miR-378a. Further investigations are worthy in elucidating these interactions and their response to BPA exposure during early development.

Keywords: BPA; Connexin; MiR-21; Oocyte maturation.