Chronic cadmium exposure causes oocyte meiotic arrest by disrupting spindle assembly checkpoint and maturation promoting factor
Chronic cadmium exposure causes oocyte meiotic arrest by disrupting spindle assembly checkpoint and maturation promoting factor
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DOI：
10.1016/j.reprotox.2020.06.009
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发表时间：
2020-09-01
影响因子：
3.3
通讯作者：
Sun, Qing-Yuan
中科院分区：
文献类型：
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作者：
Dong, Feng;Li, Jian;Sun, Qing-Yuan
镉（Cd）是一种具有生物蓄积性的重金属元素，对女性生殖系统具有潜在的毒性，但其确切的分子机制尚未明确。在本研究中，雌性小鼠连续60天暴露于0.5 mg/kg/天的CdCl2。我们发现慢性Cd暴露通过影响卵母细胞减数分裂进程（纺锤体组装、染色体排列和着丝点-微管附着被破坏）显著降低雌性小鼠的生育能力，从而导致卵母细胞非整倍体。进一步的研究表明，cd暴露的卵母细胞中MPF活性和cyclin B1表达的周期性波动可能通过影响纺锤体组装检查点蛋白Bub3而受到干扰。此外，Cd暴露诱导氧化应激，表现为卵母细胞中活性氧和细胞凋亡水平升高，导致卵母细胞质量恶化。综上所述，这些数据表明，Cd暴露会导致减数分裂过程中的分子事件中断，并通过氧化应激导致卵母细胞质量恶化，从而导致女性生育能力下降。
Cadmium (Cd) is a bioaccumulative heavy metal element with potential toxicity on the female reproductive system, but the exact molecular mechanisms have not yet been clearly defined. In this study, female mice were exposed to 0.5 mg/kg/day of CdCl2 for 60 consecutive days. We found that chronic Cd exposure significantly decreased the fecundity of female mice by affecting oocyte meiotic progression as indicated by disrupted spindle assembly, chromosome alignment and kinetochore-microtubule attachments, consequently resulting in aneuploid oocytes. Further studies showed that the periodic fluctuations of MPF activity and cyclin B1 expression were disturbed in Cd-exposed oocytes probably by affecting the spindle assembly checkpoint protein Bub3. In addition, Cd exposure induced oxidative stress as indicated by an increased level of reactive oxygen species and apoptosis in oocytes, leading to oocyte quality deterioration. Taken together, these data suggest that Cd exposure causes disrupted molecular events of meiotic progression and deterioration of oocyte quality via oxidative stress, leading to decrease of female fertility.