拟除虫菊酯杀虫剂是目前全球用量排名前10位的农药之一，在环境介质中普遍残留。我们前期的人群调查研究发现，拟除虫菊酯暴露水平与女性卵巢功能减退（premature ovarian insufficiency, POI）风险显著正相关，提示拟除虫菊酯暴露可能是影响POI发生的潜在环境危险因素。然而，目前关于拟除虫菊酯诱导POI的分子机制尚不明确。本项目拟以目前中国最为广泛使用的氯氰菊酯为典型拟除虫菊酯杀虫剂，评估长期低剂量暴露和敏感窗口期暴露对雌鼠POI类似症状的诱导；进一步研究氯氰菊酯通过调控PTEN/PI3K/PDK1/Akt通路、CRL4/DDB1/DCAF1/TET通路、DNA甲基化与去甲基化过程，诱导POI发生的分子机制。通过本项目研究，为准确、全面评估拟除虫菊酯杀虫剂的环境安全与健康风险提供科学依据和理论基础，对于加强这类农药风险管理和保障女性生殖健康具有重要的科学意义和社会意义。

Pyrethroids are one of the top 10 classes of pesticides and are ubiquitously detected in environmental media. Our previous population survey found that pyrethroid exposure was significantly and positively correlated with the risk of female premature ovarian insufficiency (POI), suggesting that pyrethroid exposure may be a potential environmental risk factor for POI. However, the molecular mechanism of pyrethroid-induced POI is unclear. In this project, we will use cypermethrin which is the most widely used in China as a typical pyrethroid insecticide to assess the induction of POI-like symptoms in female rats after long-term and low-dose exposure or sensitive window exposure. We will further investigate the regulation of cypermethrin on PTEN / PI3K / PDK1 / Akt pathway, CRL4 / DDB1 / DCAF1 / TET pathway, DNA methylation and demethylation, which explores the molecular mechanism of cypermethrin-induced POI. This project will be of scientific and social significance to provide a scientific basis and a theoretical basis for accurate and comprehensive assessment of the environmental safety and health risks of pyrethroid insecticides, and provide an important reference for determining future directions of management of pyrethroid pesticides and preventive measures of female reproductive health.