内科学
男性不育
医学
内分泌学
精子发生
化学
精子
过氧化氢酶
谷胱甘肽
异烟肼
作者
Peipei Qiao,Yingbing Zhang,Ying Yang,Ru Meng,Zhiming Xu,Xianlei Jiang,Yong Zhang,Chengtu Zhang,Jianmin Su
出处
期刊:Toxicology
[Elsevier]
日期:2021-03-23
卷期号:455: 152749-152749
被引量:1
标识
DOI:10.1016/j.tox.2021.152749
摘要
Isoniazid (INH), a synthetic first-line tuberculosis antibiotic, has been widely used in clinical treatment. It has been reported to cause toxic effects at multiple tissue sites and also increases the incidence of adverse pregnancy outcomes; but the mechanism of action of INH on the reproductive system of female mammals remains unclear. Here, we demonstrate that oral INH (40 mg/kg/day every other day for 28 days) severely affects oocyte maturation and fertilization, late blastocyst development and fertility. We found that INH could disrupt standard spindle assembly, chromosome arrangement, and actin filament dynamics, which compromised meiotic progression of mouse oocytes. INH treatment increased the level of reactive oxygen species (ROS) and activated the oxidative stress response pathway, Keap1-Nrf2. It also caused apoptosis of oocytes and mitochondrial dysfunction. Our findings demonstrate that oral INH reduces fertility and damages the mammalian reproductive system by altering cytoskeletal dynamics and Juno expression, inducing oxidative stress and apoptosis, and activating the Keap1-Nrf2 signaling pathway in mouse oocytes.
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