Low doses of bisphenol F and S affect human ovarian granulosa cells by reducing the number of active mitochondria and ATP synthesis

Abstract

Bisphenols (BPs) are a group of environmental pollutants mainly represented by bisphenol S (BPS) and F (BPF). In ovaries, BPs can accumulate in follicular fluid (FF), changing the follicular microenvironment and simultaneously affecting ovarian granulosa cells (GCs) function. In the present study, we determined the effects of BPS and BPF on oxidative stress and mitochondrial function in human ovarian GCs. Single, short-term treatment with BPs at doses reflecting their concentrations in FF (10 nM) did not affect reactive oxygen species (ROS) levels but induced mitochondrial membrane depolarization. BPF-induced mitophagy decreased the number of active mitochondria and consequently reduced the ATP production rate. The observed changes did not translate into lowered viability of GCs, but long-term treatment with BPF influenced the intrinsic apoptosis pathway by increasing caspase 9 activity without affecting apoptosis. GCs are crucial for ovarian function as they produce primary steroid hormones and regulate oocyte maturation and follicle growth. Mitochondrial dysfunction caused by BPs, manifesting as reduced ATP production in GCs, can directly cause ovarian disorders such as infertility. Therefore, this study highlights the significance of investigating the effects of BPs on reproductive health.