Nicotinic acid protects germinal vesicle oocyte meiosis against toxicity of benzo(a)pyrene in mice and humans.

Abstract

In brief: Low concentrations of benzo(a)pyrene in the follicular fluid of smokers disrupt oocyte maturation, leading to meiotic defects. Nicotinic acid (NA) partially rescues these defects, offering insights into potential strategies for protecting fertility.

Abstract: Benzo(a)pyrene (BaP), a carcinogen present in cigarette smoke, was detected in human follicular fluid at concentrations of approximately 5 nM in smokers and 7 nM in cases of assisted reproductive failure. However, whether a low concentration of BaP affects germinal vesicle (GV) oocyte maturation remains unclear. Here, we investigated the effects of 5 nM BaP on GV oocyte maturation in both mice and humans. In mice, GV oocytes were treated with 5 or 50 nM BaP, while human oocytes were exposed to 5 nM BaP. Our results demonstrated that 5 or 50 nM BaP exposure significantly inhibited first polar body extrusion during oocyte maturation. Mechanistic investigations revealed that BaP treatment downregulated Sirt1 protein expression in both GV and metaphase II (MII) stage mouse oocytes. Moreover, BaP exposure induced multiple cellular abnormalities, including spindle disorganization, cortical actin cap disruption, mitochondrial dysfunction and DNA damage in MII oocytes. Importantly, 15 μM NA supplementation increased Sirt1 expression and significantly rescued most of the abnormal effects. Subsequently, 5 nM BaP exposure impaired meiotic progression by reducing mitochondrial membrane potential and causing significant reactive oxygen species accumulation in human GV oocytes. Importantly, 15 μM NA supplementation partially rescued human GV oocytes from the toxicity of BaP during in vitro maturation (IVM). The present study indicated that a low BaP concentration in follicular fluid can significantly disrupt GV oocyte IVM, inducing meiotic defects in both mice and humans. NA has been shown to provide partial protection to GV oocyte meiosis against the toxicity of BaP during IVM.