单基甲酸精子毒性的综合计算剖析:高亲和度结合扰乱了非阻断性亚子精子症中ACE2-CYP17A1协调
Guangqiang Zhu1, Chunlin Tan2, Yugen Li2
1Department of Clinical Medicine, North Sichuan Medical College, Nanchong, Sichuan 637000, China.
Reproductive toxicology (Elmsford, N.Y.)
|September 17, 2025
概括
单乙酸 (MBzP) 是一个关键的环境风险因素,导致丸损伤和男性不孕. 这项研究揭示了其涉及ACE2 / CYP17A1相互作用的分子机制,导致炎症和受阻的精子生产.
科学领域:
- 环境健康 环境健康
- 毒理学 毒理学 毒理学
- 生殖生物学 生殖生物学
背景情况:
- 酸盐是内分泌干扰剂,与生殖毒性有关.
- 由于复杂的暴露和研究局限性,评估个体代谢物对男性不孕症的贡献具有挑战性.
研究的目的:
- 通过多omics方法识别导致丸损伤的特定甲酸代谢物.
- 阐明底层的分子机制甲酸诱导的男性不孕不育,专注于非阻塞性精 (NOA).
主要方法:
- 门德尔随机化 (MR) 用于识别致病性风险因素.
- 网络毒理学和可解释的机器学习来识别分子标.
- 基因组丰富分析 (GSEA),分子对接和动力学模拟 (MDS).
主要成果:
- 单基甲酸盐 (MBzP) 被确定为丸损伤的致病因素.
- 确定了ACE2和CYP17A1作为在塞尔托利细胞中过度表达的核心分子标.
- MBzP与ACE2/CYP17A1结合会破坏功能,激活炎症/亡通路并抑制精子生成.
结论:
- 阐明了导致男性不孕症的MBzP-ACE2/CYP17A1分子轴.
- 确定了参与甲酸毒性的关键途径 (TGF-β,p53,干扰素反应).
- 为精确治疗男性不孕症提供了新的分子标.
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