产前DEHP暴露会通过持续干扰类固醇基因表达来诱导终身丸毒性
Qigen Xie1,2, Haiming Cao3, Hanchao Liu4
1Department of Pediatric Surgery, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Translational andrology and urology
|April 9, 2024
概括
产前暴露于二-2-乙烯基甲酸盐 (DEHP) 通过破坏类固醇基因表达导致终身丸毒性. 这种干扰与性发育障碍,男性生殖问题以及加速生殖衰老有关.
科学领域:
- 内分泌学 在内分泌学.
- 毒理学 毒理学 毒理学
- 生殖生物学 生殖生物学
背景情况:
- 流行病学研究将产前二甲基甲酸 (DEHP) 暴露与性发育障碍 (DSD),男性生殖障碍和生殖衰老联系起来.
- 怀疑DEHP通过类固醇基因表达干扰抑制丸合成诱导丸毒性的潜力,但尚未完全确立.
研究的目的:
- 调查产前DEHP暴露对小鼠男性生殖健康的长期影响.
- 阐明DEHP暴露影响丸功能的机制,重点关注类固醇基因表达.
主要方法:
- C57BL/6JGpt雄性小鼠在妊娠期间暴露于不同剂量的DEHP.
- 在新生儿,青春期后和中年阶段评估丸毒性,评估生殖器发育,丸水平,精液质量和丸形态.
- 使用qPCR和西部斑块分析了类固醇基因表达;使用TM3细胞来验证MEHP对合成的影响.
主要成果:
- 产前的DEHP暴露导致新生儿立即丸损伤 (降低阴茎距离,丸激素),青春期后小鼠的DSD,中年小鼠的生殖衰老 (肥胖,降低丸/精液质量,丸缩),特别是在高剂量时.
- 在RNA和蛋白质水平上,DEHP暴露持续扰乱了类固醇基因表达 (Hsd3b2,Hsd17b3).
- 通过干扰 Hsd3b2 和 Hsd17b3 基因表达,暴露于 Mono-(2-ethylhexyl) 甲酸盐 (MEHP) 抑制了 TM3 细胞中的合成.
结论:
- 产前暴露于DEHP会导致持续的,终身的丸毒性.
- 该机制涉及对类固醇基因表达的持续干扰,将产前暴露与DSD,成年男性疾病和生殖衰老联系起来.
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