Maternal exposure to dibutyl phthalate regulates MSH6 crotonylation to impair homologous recombination in fetal oocytes

作者全名："Ma, Yidan; Mu, Xinyi; Gao, Rufei; Zhang, Yan; Geng, Yanqing; Chen, Xuemei; Yin, Xin; Li, Fangfang; He, Junlin"

作者地址："[Ma, Yidan; Gao, Rufei; Zhang, Yan; Geng, Yanqing; Chen, Xuemei; Yin, Xin; Li, Fangfang; He, Junlin] Chongqing Med Univ, Sch Publ Hlth, Dept Hlth Toxicol, Chongqing 400016, Peoples R China; [Ma, Yidan; Mu, Xinyi; Gao, Rufei; Zhang, Yan; Geng, Yanqing; Chen, Xuemei; Yin, Xin; Li, Fangfang; He, Junlin] Chongqing Med Univ, Joint Int Res Lab Reprod & Dev, Chongqing 400016, Peoples R China; [Mu, Xinyi; Geng, Yanqing] Chongqing Med Univ, Coll Basic Med, Chongqing 400016, Peoples R China; [He, Junlin] 1 Yixueyuan Rd, Chongqing 400016, Peoples R China"

通信作者："He, JL (通讯作者)，1 Yixueyuan Rd, Chongqing 400016, Peoples R China."

来源：JOURNAL OF HAZARDOUS MATERIALS

ESI学科分类：ENGINEERING

WOS号：WOS:001003388500001

JCR分区：Q1

影响因子：12.2

年份：2023

卷号：455

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Crotonylation; Dibutyl phthalate; MSH6; NHEJ; Homologous recombination

摘要："Homologous recombination (HR) during early oogenesis repairs programmed double-strand breaks (DSBs) to ensure female fertility and offspring health. The exposure of fetal ovaries to endocrine disrupting chemicals (EDCs) can cause reproductive disorders in the adulthood. The EDC dibutyl phthalate (DBP) is widely distributed in flexible plastic products, leading to ubiquitous human exposure. Here, we report that maternal exposure to DBP caused gross aberrations in meiotic prophase I of fetal oocytes, including delayed progression, impaired DNA damage response, uncoupled localization of DMC1 and RAD51, and decreased HR. However, programmed DSBs were efficiently repaired. DBP exposure negatively regulated lysine crotonylation (Kcr) of MSH6. Similar meiotic defects were observed in fetal ovaries with targeted disruption of Msh6, and mutation of K544cr of MSH6 impaired its association with Ku70, thereby promoting non-homologous end joining (NHEJ) and inhibiting HR. Unlike mature F1 females, F2 female mice exhibited premature follicular activation, precocious puberty, and anxiety-like behaviors. Therefore, DBP can influence early meiotic events, and Kcr of MSH6 may regulate preferential induction of HR or NHEJ for DNA repair during meiosis."

基金机构：National Natural Science Foundation of China [32070851]; Special Professorship Project of Chongqing Medical University [2021-215]; Outstanding Graduate Student Cultivation Program of Chongqing Medical University [BJRC202114]

基金资助正文："Acknowledgements This work was supported by grants from the National Natural Science Foundation of China (Grant No. 32070851) , the Special Professorship Project of Chongqing Medical University (2021-215) , and the Outstanding Graduate Student Cultivation Program of Chongqing Medical University (No. BJRC202114) . Image materials in graphic ab-stract were source from BioRender (https://biorender.com /) ."