College of Veterinary Medicine, Northwest A&F University, Yangling, Shaanxi Province 712100, PR China.
Academy of Animal Science and Veterinary Medicine, Qinghai University, Xining, Qinghai Province 810003, PR China.
Toxicol Appl Pharmacol. 2019 Sep 15;379:114684. doi: 10.1016/j.taap.2019.114684. Epub 2019 Jul 17.
Cadmium (Cd), a known metal contaminant, is widespreadly used in industry, thereby human health is severely affected through the way of occupational and environmental exposure. The adverse effects of the exposure to Cd on the female reproductive system, especially oocyte maturation and fertility have not been clearly defined. In this study, we found the arrested development of ovaries and uteri after Cd exposure and determined oocyte quality via assessing the key regulators during meiotic maturation and fertilization. We found that Cd exposure impeded the mouse oocyte meiotic progression by disrupting the normal spindle assembly, chromosome alignment and actin cap formation. Besides, exposure to Cd induced oxidative stress with the increased reactive oxygen species and apoptosis levels, leading to abnormal mitochondrial distribution, insufficient energy supply, and DNA damage, which ultimately led to oocyte quality deterioration. We also analyzed the effects of cadmium on epigenetic modifications, and the levels of 5mC, H3K9me3 and H3K9ac decreased after acute exposure to cadmium. Further experiments showed that the litter size in Cd-exposed female mice reduced, thereby indicating increased reproductive Cd toxicity. In conclusion, Cd exposure impairs oocyte maturation and fertilization ability induced by oxidative stress, early apoptosis and epigenetic modifications, which lead to the decrease of female fertility.
镉（Cd）是一种已知的金属污染物，广泛应用于工业生产，从而通过职业和环境暴露的方式严重影响人类健康。暴露于镉对女性生殖系统的不良影响，特别是卵母细胞成熟和生育能力，尚未明确界定。在这项研究中，我们发现镉暴露后卵巢和子宫发育停滞，并通过评估减数分裂成熟和受精过程中的关键调节因子来确定卵母细胞质量。我们发现，镉暴露通过破坏正常纺锤体组装、染色体排列和肌动蛋白帽形成，阻碍了小鼠卵母细胞的减数分裂进程。此外，暴露于镉会引起氧化应激，导致活性氧和细胞凋亡水平增加，从而导致线粒体分布异常、能量供应不足和 DNA 损伤，最终导致卵母细胞质量恶化。我们还分析了镉对表观遗传修饰的影响，急性暴露于镉后，5mC、H3K9me3 和 H3K9ac 的水平降低。进一步的实验表明，暴露于镉的雌性小鼠的产仔数减少，这表明生殖系统镉毒性增加。总之，镉暴露通过氧化应激、早期细胞凋亡和表观遗传修饰损害卵母细胞的成熟和受精能力，导致女性生育能力下降。
