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

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

  • Chem Biol Interact. 2022 Sep 25:365:110085. doi: 10.1016/j.cbi.2022.110085.
Jie Yang 1,  Hanting Xu 2,  Rufei Gao 1,  Xueqing Liu 1,  Junlin He 1,  Meilin Zhou 1,  Yubin Ding 1,  Fangfang Li 1,  Yanqing Geng 2,  Xinyi Mu 2,  Taihang Liu 1,  Yingxiong Wang 2,  Xuemei Chen 3
Affiliations

Affiliations

  • 1 Laboratory of Reproductive Biology, School of Public Health, Chongqing Medical University, Chongqing, 400016, PR China; Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, 400016, PR China.
  • 2 Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, 400016, PR China; College of Basic Medicine, Chongqing Medical University, Chongqing, 400016, PR China.
  • 3 Laboratory of Reproductive Biology, School of Public Health, Chongqing Medical University, Chongqing, 400016, PR China; Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Chongqing, 400016, PR China. Electronic address: [email protected].
PMID: 35940284 DOI: 10.1016/j.cbi.2022.110085
Abstract

Benzo(a)pyrene (BaP) is a well-known environmental endocrine pollutant, which has ovarian toxicity in mammals. Ovarian corpus luteum (CL), as the main source of progesterone synthesis in early pregnant female, requires 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 mitochondrial 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.

Keywords

BaP; Corpus luteum; Melatonin receptors; Mitochondrial dysfunction; Ramelteon.

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