Adverse effects of 2-Methoxyestradiol on mouse oocytes during reproductive aging

  • Chem Biol Interact. 2023 Jan 5:369:110277. doi: 10.1016/j.cbi.2022.110277.
Xiuying Jiang  1 ,  Xiangning Xu  2 ,  Bicheng Wang  2 ,  Ke Song  2 ,  Jiaqi Zhang  2 ,  Ye Chen  2 ,  Ying Tian  2 ,  Jing Weng  2 ,  Yuanjing Liang  2 ,  Wei Ma  3
Affiliations
  • 1. Devision of Sport Anatomy, School of Sport Science, Beijing Sport University, Beijing, 100084, China.
  • 2. Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China.
  • 3. Department of Histology and Embryology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, China. Electronic address: [email protected].
PMID: 36414027 DOI: 10.1016/j.cbi.2022.110277
Abstract

2-Methoxyestradiol (2-ME2) is a metabolite of 17β-estradiol and is currently in clinical trials as an antitumor agent. Here we found 2-ME2 level remains stable in the local environment of ovaries but declines in serum in aging mice, and exogenous 2-ME2 impacts the meiotic maturation of mouse oocytes in dose-dependent manner. In vitro 2-ME2 application arrested oocytes at metaphase I (MI), with abnormal spindle structure and chromosome alignment. 2-ME2 exposure induced excessive production of Reactive Oxygen Species (ROS) and malondialdehyde, as well as accelerated Apoptosis progression. 2-ME2 unbalanced mitochondrial dynamics by increasing DRP1 and MFN1 while decreasing Opa1. Similar phenotypes were also observed in oocytes from mice injected intraperitoneally with 2-ME2. Taken together, this study indicates 2-ME2 exposure impairs oocyte meiotic maturation through inducing mitochondrial imbalance, oxidative stress and Apoptosis. The gradual decline in oocyte quality and quantity may be associated with the stable 2-ME2 in ovaries during female reproductive aging.

Keywords
2-Methoxyestradiol; Apoptosis; Mitochondria; Oocyte meiosis; Ovary aging; ROS.
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