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

Benzo(a)pyrene (BaP) 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 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 nM or 50 nM BaP, while human oocytes were exposed to 5 nM BaP. Our results demonstrated that 5 nM 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 nicotinic acid (NA) supplementation increased Sirt1 expression and significantly rescued most of the abnormal effects. Subsequently, 5 nM BaP exposure impaired meiotic progression via reducing mitochondrial membrane potential and causing significant reactive oxygen species (ROS) accumulation in human GV oocyte also. Importantly, 15 μM NA supplementation partially rescued human GV oocytes from the toxicity of BaP during IVM. The present study indicated that 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.