2. Academic Validation
  3. Melatonin alleviates benzo(a)pyrene-induced ovarian corpus luteum dysfunction by suppressing excessive oxidative stress and apoptosis

Melatonin alleviates benzo(a)pyrene-induced ovarian corpus luteum dysfunction by suppressing excessive oxidative stress and apoptosis

  • Ecotoxicol Environ Saf. 2021 Jan 1;207:111561. doi: 10.1016/j.ecoenv.2020.111561.
Hanting Xu 1,  Xinyi Mu 2,  Yubin Ding 3,  Qiman Tan 4,  Xueqing Liu 5,  Junlin He 6,  Rufei Gao 7,  Nanyan Li 8,  Yanqing Geng 9,  Yingxiong Wang 10,  Xuemei Chen 11
Affiliations

Affiliations

  • 1 Laboratory of Reproductive Biology, School of Public Health and Management, Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Box 197, No.1 Yixueyuan Road, Yuzhong District, Chongqing 400016, PR China. Electronic address: 1445113408@qq.com.
  • 2 Laboratory of Reproductive Biology, School of Public Health and Management, Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Box 197, No.1 Yixueyuan Road, Yuzhong District, Chongqing 400016, PR China. Electronic address: 102696@cqmu.edu.cn.
  • 3 Laboratory of Reproductive Biology, School of Public Health and Management, Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Box 197, No.1 Yixueyuan Road, Yuzhong District, Chongqing 400016, PR China. Electronic address: dingyb@cqmu.edu.cn.
  • 4 Laboratory of Reproductive Biology, School of Public Health and Management, Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Box 197, No.1 Yixueyuan Road, Yuzhong District, Chongqing 400016, PR China. Electronic address: 398859954@qq.com.
  • 5 Laboratory of Reproductive Biology, School of Public Health and Management, Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Box 197, No.1 Yixueyuan Road, Yuzhong District, Chongqing 400016, PR China. Electronic address: cqmu_liuxueqing@126.com.
  • 6 Laboratory of Reproductive Biology, School of Public Health and Management, Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Box 197, No.1 Yixueyuan Road, Yuzhong District, Chongqing 400016, PR China. Electronic address: hejunlin@cqmu.edu.cn.
  • 7 Laboratory of Reproductive Biology, School of Public Health and Management, Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Box 197, No.1 Yixueyuan Road, Yuzhong District, Chongqing 400016, PR China. Electronic address: gao_ru_fei@cqmu.edu.cn.
  • 8 Laboratory of Reproductive Biology, School of Public Health and Management, Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Box 197, No.1 Yixueyuan Road, Yuzhong District, Chongqing 400016, PR China. Electronic address: 1095256660@qq.com.
  • 9 Laboratory of Reproductive Biology, School of Public Health and Management, Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Box 197, No.1 Yixueyuan Road, Yuzhong District, Chongqing 400016, PR China. Electronic address: 102813@cqmu.edu.cn.
  • 10 Laboratory of Reproductive Biology, School of Public Health and Management, Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Box 197, No.1 Yixueyuan Road, Yuzhong District, Chongqing 400016, PR China. Electronic address: yxwang@cqmu.edu.cn.
  • 11 Laboratory of Reproductive Biology, School of Public Health and Management, Joint International Research Laboratory of Reproduction & Development, Chongqing Medical University, Box 197, No.1 Yixueyuan Road, Yuzhong District, Chongqing 400016, PR China. Electronic address: chenxuemei@cqmu.edu.cn.
PMID: 33254415 DOI: 10.1016/j.ecoenv.2020.111561
Abstract

Benzo(a)pyrene (B(a)P) is a widespread persistent organic pollutant (POP) and a well-known endocrine disruptor. Exposure to BaP is known to disrupt the steroid balance and impair embryo implantation, but the mechanism under it remains unclear. The corpus luteum (CL), the primary source of progesterone during early pregnancy, plays a pivotal role in embryo implantation and pregnancy maintenance. The inappropriate luteal function may result in implantation failure and spontaneous abortions. Therefore, this study was conducted to assess the effects and potential mechanisms of B(a)P on the CL function. Our results showed that pregnant mice received B(a)P displayed impaired embryo implantation and dysfunction of ovarian CL. The estrogen and progesterone levels decreased by B(a)P. In vitro, exposure to BPDE, which is the metabolite of B(a)P, affected the luteinization of granular cell KK-1. Additionally, melatonin and its receptors, which are important for ovarian function and anti-oxidative damage, were affected by B(a)P or BPDE. B(a)P or BPDE-treated alone impaired antioxidant capacity of ovarian granulosa cells, caused an increasing of ROS and cell Apoptosis, and disrupted the PI3K/Akt/GSK3β signaling pathway in vivo and in vitro. Co-treatment with melatonin alleviated B(a)P or BPDE-induced CL dysfunction by ameliorating oxidative stress, counteracting phosphorylation of PI3K/Akt/GSK3β signaling pathway, decreasing the Apoptosis of the ovarian cells. Moreover, activation of the Melatonin Receptor by ramelteon in KK-1 cells exhibits an analogous protective effect as melatonin. In conclusion, our findings not only firstly clarify the potential mechanisms of BaP-induced CL dysfunction, but also extend the understanding about the ovarian protection of melatonin and its receptors against B(a)P exposure.

Keywords

10-Epoxide; 8-Dihydrodiol-9; Apoptosis; Benzo(a)pyrene; Benzo(a)pyrene-7; Melatonin; Ovarian corpus luteum function; Reactive oxygen species.

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