DDT和DDE对胎盘胆固醇受体的影响
Recep Uyar1, Yağmur Turgut1, H Tolga Çelik2
1Ankara University, Graduate School of Health Sciences, Ankara 06070, Turkiye.
Reproductive toxicology (Elmsford, N.Y.)
|April 14, 2024
概括
产前暴露于二二三乙 (DDT) 和其代谢物DDE会增加胎盘肌酸受体的表达. 这一发现突显了有机农药对胎儿发育和胎盘功能的潜在影响.
科学领域:
- 环境毒理学环境毒理学
- 生殖生物学 生殖生物学
- 分子药理学分子药理学
背景情况:
- 胎盘胆固醇系统调节重要功能,包括新陈代谢,血管度,发育和神经传递.
- 持久性有机农药,特别是像DDT这样的有机农药 (OCP),可以破坏表观遗传调节和分子通路.
- 尽管有禁令,但环境中DDT的污染导致了不可避免的产前暴露.
研究的目的:
- 研究2.4'-DDT,4.4'-DDT和4.4'-DDE对人类胎盘胆固醇系统的影响.
- 评估这些化合物暴露后胆固醇基因表达的变化.
主要方法:
- 对40个人类胎盘进行DDT及其代谢物的查.
- 在阳性样本中量化OCP度.
- RNA测序 (RNA-Seq) 用于识别差异表达的基因.
- 免疫组织化学和体外分析 (HTR8/SVneo细胞) 验证基因表达变化.
主要成果:
- 42.50%的胎盘样本检测出DDT和/或DDE的阳性.
- 在暴露样本中,RNA-Seq揭示了2396个差异表达的基因,CHRM1,CHRNA1,CHRNG和CHRNA2的显著上调.
- 实验室研究证实,在DDT/DDE治疗后,肌糖受体 (CHRM1,CHRM3) 和尼古丁受体 (CHRN1) 的mRNA和蛋白质表达增加.
结论:
- 在子宫内暴露于DDT显著影响胎盘胆固醇系统,主要是通过增加肌肉蛋白受体表达.
- 这种受体的上调可能会增加胎盘对乙胆的敏感性.
- 这些发现强调了OCPs对胎盘功能和胎儿发育的潜在不良影响.
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