Late gestational exposure to fenvalerate impacts ovarian reserve in neonatal mice via YTHDF2-mediated P-body assembly

作者全名：He, Fei; Mu, Xinyi; Zhang, Yan; Wang, Yongheng; Geng, Jianwei; Geng, Yanqing; Ma, Yidan; Yin, Xin; Gao, Rufei; Chen, Xuemei; He, Junlin

作者地址：[He, Fei; Zhang, Yan; Ma, Yidan; Yin, Xin; Gao, Rufei; Chen, Xuemei; He, Junlin] Chongqing Med Univ, Sch Publ Hlth, Dept Hlth Toxicol, Chongqing 400016, Peoples R China; [He, Fei; Mu, Xinyi; Zhang, Yan; Wang, Yongheng; Geng, Jianwei; Geng, Yanqing; Ma, Yidan; Yin, Xin; Gao, Rufei; Chen, Xuemei; He, Junlin] Chongqing Med Univ, Joint Int Res Lab Reprod & Dev, Chongqing 400016, Peoples R China; [Mu, Xinyi; Wang, Yongheng; Geng, Jianwei; Geng, Yanqing] Chongqing Med Univ, Sch Basic Med, Chongqing 400016, Peoples R China

通信作者：He, JL (通讯作者)，Chongqing Med Univ, Sch Publ Hlth, Dept Hlth Toxicol, Chongqing 400016, Peoples R China.

来源：SCIENCE OF THE TOTAL ENVIRONMENT

ESI学科分类：ENVIRONMENT/ECOLOGY

WOS号：WOS:001218362200001

JCR分区：Q1

影响因子：8.2

年份：2024

卷号：925

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Fenvalerate (FEN); Primordial follicle formation; m6A; YTHDF2; P-body

摘要：Fenvalerate (FEN), a type II pyrethroid pesticide, finds extensive application in agriculture, graziery and public spaces for pest control, resulting in severe environmental pollution. As an environmental endocrine disruptor with estrogen-like activity, exposure to FEN exhibited adverse effects on ovarian functions. Additionally, the presence of the metabolite of FEN in women's urine shows a positive association with the risk of primary ovarian insufficiency (POI). In mammals, the primordial follicle pool established during the early life serves as a reservoir for storing all available oocytes throughout the female reproductive life. The initial size of the primordial follicle pool and the rate of its depletion affect the occurrence of POI. Nevertheless, there is very limited research about the impact of FEN exposure on primordial folliculogenesis. In this study, pregnant mice were orally administrated with 0.2, 2.0 and 20.0 mg/kg FEN from 16.5 to 18.5 days post-coitus (dpc). Ovaries exposed to FEN exhibited the presence of large germ-cell cysts that persist on 1 days post-parturition (1 dpp), followed by a significant reduction in the total number of oocytes in pups on 5 dpp. Moreover, the levels of m6A-RNA and its associated proteins METTL3 and YTHDF2 were significantly increased in the ovaries exposed to FEN. The increased YTHDF2 promoted the assembly of the cytoplasmic processing bodies (P-body) in the oocytes, accompanied with altered expression of transcripts. Additionally, when YTHDF2 was knocked-down in fetal ovary cultures, the primordial folliculogenesis disrupted by FEN exposure was effectively restored. Further, the female offspring exposed to FEN displayed ovarian dysfunctions reminiscent of POI in early adulthood, characterized by decreases in ovarian coefficient and female hormone levels. Therefore, the present study revealed that exposure to FEN during late pregnancy disrupted primordial folliculogenesis by YTHDF2-mediated P-body assembly, causing enduring adverse effects on female fertility.

基金机构：Special Professorship Project of Chongqing Medical University [2021-215]

基金资助正文：This study was supported by grants from the Special Professorship Project of Chongqing Medical University (2021-215) . Besides, we thank Biorender, the free online resource, for providing image materials for graphical abstract.