Exposure to Benzo(a)pyrene damages mitochondrial function via suppressing mitochondrial melatonin receptors in ovarian corpus luteum during early pregnancy

作者全名："Yang, Jie; Xu, Hanting; Gao, Rufei; Liu, Xueqing; He, Junlin; Zhou, Meilin; Ding, Yubin; Li, Fangfang; Geng, Yanqing; Mu, Xinyi; Liu, Taihang; Wang, Yingxiong; Chen, Xuemei"

作者地址："[Yang, Jie; Gao, Rufei; Liu, Xueqing; He, Junlin; Zhou, Meilin; Ding, Yubin; Li, Fangfang; Liu, Taihang; Chen, Xuemei] Chongqing Med Univ, Sch Publ Hlth, Lab Reprod Biol, Chongqing 400016, Peoples R China; [Yang, Jie; Xu, Hanting; Gao, Rufei; Liu, Xueqing; He, Junlin; Zhou, Meilin; Ding, Yubin; Li, Fangfang; Geng, Yanqing; Mu, Xinyi; Liu, Taihang; Wang, Yingxiong; Chen, Xuemei] Chongqing Med Univ, Joint Int Res Lab Reprod & Dev, Chongqing 400016, Peoples R China; [Xu, Hanting; Geng, Yanqing; Mu, Xinyi; Wang, Yingxiong] Chongqing Med Univ, Coll Basic Med, Chongqing 400016, Peoples R China"

通信作者："Chen, XM (通讯作者)，Chongqing Med Univ, Sch Publ Hlth, Lab Reprod Biol, Chongqing 400016, Peoples R China."

来源：CHEMICO-BIOLOGICAL INTERACTIONS

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000848631600003

JCR分区：Q1

影响因子：5.1

年份：2022

卷号：365

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：BaP; Corpus luteum; Mitochondrial dysfunction; Melatonin receptors; Ramelteon

摘要："Benzo(a)pyrene (BaP) is a well-known environmental endocrine pollutant, which has ovarian toxicity in mam-mals. Ovarian corpus luteum (CL), as the main source of progesterone synthesis in early pregnant female, re-quires a large number of mitochondria for energy supply. We previously demonstrated that BaP and its metabolite benzo(a)pyren-7, 8-dihydrodiol-9, 10-epoxide (BPDE) inhibited the ovarian melatonin receptors (MTRs) expression and decreased the levels of estrogen and progesterone during early pregnancy in mice. Emerging researches show that MTRs also exist on mitochondrial membrane and participate in the regulation of mitochondrial function. However, the relationship between BaP, MTRs on mitochondrial membrane and mito-chondrial function remains unknown. Consequently, this study focuses on the effect and potential mechanism of BaP on ovarian luteal mitochondrial function during early pregnancy. We found that BaP and its metabolite BPDE decreased MTRs in early pregnant CL and luteinized KGN cells, especially in mitochondria. Furthermore, BaP or BPDE up-regulated the expression of SIRT3, Mfn2 and Drp-1, damaged mitochondrial morphology and decreased the MMP and the ATP levels, thereby causing mitochondrial dysfunction. Notably, activation of the MTRs on mitochondrial membrane by MTRs agonist ramelteon partially alleviated BPDE-induced up-regulation of SIRT3, Mfn2 and Drp-1, reduced mitochondrial fragmentation and enhanced the MMP and the ATP levels, thus restoring the expression of steroid rate-limiting enzymes. Together, these findings firstly proved that BaP and BPDE down-regulate MTRs on mitochondrial membrane, and further injure mitochondrial function in early pregnant rats' CL, which provides a new insight for understanding the exact mechanism of the BaP-induced ovarian toxicity."

基金机构：National Natural Science Foundation of China [81573175]; Natural Science Foundation of Chongqing [cstc2018jcyjAX0315]

基金资助正文："The research was supported by National Natural Science Foundation of China (81573175) , and the Natural Science Foundation of Chongqing (cstc2018jcyjAX0315) ."