Gao Min, Qiu Yanling, Li Dungao, Zhan Shaoquan, Chen Bohong, Cao Tianqi, Huang Junjiu, Chen Zhiyun
Reproduction. 2025 Mar 19;169(4). doi: 10.1530/REP-24-0364. Print 2025 Apr 1.
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.
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.
吸烟者卵泡液中低浓度的苯并(a)芘会破坏卵母细胞成熟，导致减数分裂缺陷。烟酸（NA）可部分挽救这些缺陷，为保护生育能力的潜在策略提供了见解。
苯并(a)芘（BaP）是香烟烟雾中的一种致癌物，在人类卵泡液中被检测到，吸烟者体内浓度约为5 nM，辅助生殖失败病例中浓度约为7 nM。然而，低浓度的BaP是否会影响生发泡（GV）卵母细胞成熟仍不清楚。在此，我们研究了5 nM BaP对小鼠和人类GV卵母细胞成熟的影响。在小鼠中，GV卵母细胞用5或50 nM BaP处理，而人类卵母细胞暴露于5 nM BaP。我们的结果表明，暴露于5或50 nM BaP会显著抑制卵母细胞成熟过程中的第一极体排出。机制研究表明，BaP处理会下调GV期和中期II（MII）期小鼠卵母细胞中Sirt1蛋白的表达。此外，BaP暴露会诱导多种细胞异常，包括MII期卵母细胞中的纺锤体紊乱、皮质肌动蛋白帽破坏、线粒体功能障碍和DNA损伤。重要的是，补充15 μM NA可增加Sirt1表达，并显著挽救大部分异常效应。随后，5 nM BaP暴露通过降低线粒体膜电位并导致人类GV卵母细胞中大量活性氧积累，损害减数分裂进程。重要的是，在体外成熟（IVM）过程中，补充15 μM NA可部分挽救人类GV卵母细胞免受BaP的毒性影响。本研究表明，卵泡液中低浓度的BaP可显著破坏GV卵母细胞IVM，在小鼠和人类中诱导减数分裂缺陷。已证明NA在IVM期间可为GV卵母细胞减数分裂提供部分保护，使其免受BaP的毒性影响。
