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EHDPP诱导了精子细胞的增殖抑制和亡:从转录组和代谢组资料的见解

Ying Wang¹, An-Liang Guo¹, Yang Xu²

¹Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan 250012, PR China.

Ecotoxicology and environmental safety

|August 14, 2024

概括

2-乙二酸 (EHDPP) 通过破坏DNA和破坏核酸代谢,损害男性生育能力,导致精子运动率降低. 抗氧化剂N-乙半氨酸 (NAC) 在小鼠和细胞模型中逆转了这些毒性作用.

科学领域:

生殖毒理学生殖毒理学
环境健康环境健康
生物化学生化学

背景情况:

2-乙烯二酸 (EHDPP) 广泛使用,并与男性生殖问题有关.
以前的研究表明,EHDPP会影响日本男性的生殖行为和生育能力.
对于EHDPP对精子生成的具体影响尚不清楚.

研究的目的:

为了调查EHDPP的男性生殖毒性.
阐明EHDPP诱导的生殖毒性的潜在机制.
评估N-乙半氨酸 (NAC) 对EHDPP毒性的潜在保护作用.

主要方法:

用不同剂量的EHDPP治疗人类精子细胞系GC-2和雄性CD-1小鼠.
评估精子数量,运动性,细胞增殖,细胞亡和氧化应激.
利用代谢组和转录组分析来确定机制.
在体内和体外研究了NAC的逆转效应.

主要成果:

在小鼠的丸和GC-2细胞中,EHDPP抑制了增殖和诱导了亡.
代谢组和转录组数据表明核酸代谢障碍和DNA损伤.
过度的活性氧物种 (ROS) 生产被确定为DNA损伤和线粒体功能障碍的原因.
补充NAC可以逆转EHDPP诱导的DNA损伤,抑制繁殖,亡,降低精子运动.

结论:

由EHDPP诱导的生殖细胞增殖抑制和亡是由ROS引起的DNA损伤和核酸代谢障碍介导的.
这些机制最终导致精子运动率的下降.
NAC证明了对EHDPP的不良生殖结果的保护作用.

关键词:

2 - 乙基基二基酸盐抗氧化试剂是一种抗氧化试剂.男性生殖毒性有毒性代谢组中的代谢.转录组转录组就是一个转录组.

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