持久性有机污染物在体外对人类卵巢的能量稳态进行调节
Tianyi Li1, Richelle D Björvang2, Jie Hao3
1Department of Gynecology and Reproductive Medicine, Karolinska University Hospital, Stockholm, Sweden; Division of Obstetrics and Gynecology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
Environment international
|May 3, 2024
概括
持久性有机污染物 (POP) 破坏人类的卵巢能量代谢,影响卵泡生长,并可能导致不孕. 这项研究揭示了将POP暴露与生殖健康问题的新机制.
科学领域:
- 生殖毒理学 生殖毒理学
- 环境健康 环境健康
- 细胞的新陈代谢
背景情况:
- 持久性有机污染物 (POP) 与野生动物数量下降和人类不孕症有关.
- 遗留的POP如DDT和PCB仍然在生育年龄的女性中被检测到.
- 影响卵巢功能和生育能力的机制仍然不清楚.
研究的目的:
- 研究五种常见的POPs (HCB,DDE,PCB156,PCB180,PFOS) 和它们的混合物对人类卵巢细胞和组织的体外影响.
- 阐明POP诱导的卵巢功能障碍背后的分子机制.
- 为了确定人类卵巢中POPs的关键细胞点.
主要方法:
- 暴露人类卵巢细胞系 (COV434,KGN,PA1),卵巢初级细胞和卵巢组织在流行病学上相关的POP度.
- 用RNA测序分析基因表达变化,重点关注能量代谢.
- 定量PCR (qPCR) 和免疫染用于验证目标基因和蛋白质的表达.
- 在卵巢组织培养中评估ATP生产和卵泡生长/缩.
主要成果:
- POPs显著改变了与中央能量代谢 (糖解,氧化酸化,脂肪酸代谢,ROS) 相关的基因表达.
- 关键的代谢酶 (ENO1,LDHA,COX4I1,ATP5A,GPX4) 被确定为POP的目标.
- 除了PCB180外,POP暴露减少了健康的卵泡比例,并增加了卵巢组织中的卵泡缩.
- 暴露于POP会改变卵巢细胞和组织中的ATP产生.
结论:
- 细胞能量代谢的破坏是POP诱导的卵巢功能障碍的一个新机制.
- 通过改变关键的代谢途径,POPs干扰人类卵巢卵泡的生长和健康.
- 这些发现为与POP暴露相关的生殖健康风险提供了新的见解.
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