Role of miR-128-3p/Nrf2 Axis in DPhP-Induced GC-2spd(ts) Apoptosis and Inhibition of Cellular Autophagy.

Organophosphorus flame retardants (OPFRs) are recognized as potential endocrine disruptors. Several studies have demonstrated that contamination with OPFRs increases the risk of infertility. Our prior research showed that inhibition of the nuclear factor erythroid-derived 2-related factor (Nrf2)/p53 signaling pathway is an essential regulator of DPhP-induced reproductive injury. In this study, we aimed to uncover potential epigenetic mechanisms involved in DPhP-induced GC-2 cell dysfunction. Our results established that DPhP promoted miR-128-3p expression in GC-2 cells, targeted the Nrf2 signaling pathway, thereby suppressing its activity, and thus inhibited autophagy to promote apoptosis. These findings indicate that DPhP causes reproductive damage and potentially modulates autophagy and apoptosis in GC-2 cells through the miR-128-3p/Nrf2 regulatory axis. Our results further elucidated the possible mechanism of DPhP-induced reproductive damage and provided new clues to study the potential reproductive toxicity of OPFRs.