Nicotinic acid protected germinal vesicle oocyte meiosis against toxicity of benzo(a)pyrene during maturation

Abstract

Abstract Accumulating evidence has demonstrated that high concentration of benzo(a)pyrene (BaP) causes oocyte and embryo developmental arrest or death resulting in early pregnancy loss. However, whether the physiological concentration of BaP exposure affects GV oocyte maturation in exposure population remains unclear. Here, we evaluate the effects of human ovarian follicular fluid concentrations of BaP on mouse and human germinal vesicle (GV) oocyte maturation. Moreover, we examined whether nicotinic acid (NA) reversed GV meiotic failure caused by BaP during in vitro maturation (IVM). We used human ovarian follicular fluid concentrations of 5 nM BaP and/or a relatively high concentration of 50 nM group to treat GV oocytes during IVM in mice and human. We found 5 nM/50 nM BaP exposure significantly reduced first polar body extrusion during mouse GV oocytes maturation. Sirt1 protein expression decreased after BaP treatment in mouse oocytes. Moreover, BaP exposure disorganized spindle and chromosome arrangement, disrupted cortical actin cap, impaired mitochondrial redistribution, and caused DNA damage in IVM metaphase II (MII) mouse oocytes. Importantly, NA supplementation (15µM) increased Sirt1 expression and significantly rescued most of the abnormal effects. We then explored the effect of 5 nM BaP on human GV oocytes, a concentration close to that in human ovarian follicular fluid, and found that BaP caused GV meiotic failure by increasing mitochondrial membrane potential and markedly elevating reactive oxygen species (ROS) levels. Finally, we showed that 15 µM NA supplementation partially rescued human GV oocytes from the toxicity of 5 nM BaP during IVM. Our study indicates that physiological concentrations of BaP could seriously disrupt GV oocyte IVM and cause meiotic defects leading to oocyte arrest in both mice and humans. NA partially protects GV oocyte meiosis against BaP toxicity during IVM.