Melatonin improves the quality of rotenone-exposed mouse oocytes through association with histone modifications

Xiaofei Wang; Huiying Li; Hongbei Mu; Shaozhe Zhang; Yuanyuan Li; Xiaotao Han; Ling Zhang; Wenpei Xiang

doi:10.1016/j.ecoenv.2023.115186

Melatonin improves the quality of rotenone-exposed mouse oocytes through association with histone modifications

Ecotoxicol Environ Saf. 2023 Jun 30:262:115186. doi: 10.1016/j.ecoenv.2023.115186. Online ahead of print.

Authors

Xiaofei Wang¹, Huiying Li², Hongbei Mu³, Shaozhe Zhang⁴, Yuanyuan Li³, Xiaotao Han⁵, Ling Zhang⁶, Wenpei Xiang⁷

Affiliations

¹ Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; The First College of Clinical Medical Science, China Three Gorges University, Yichang, China.
² The First College of Clinical Medical Science, China Three Gorges University, Yichang, China.
³ Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁴ Wuhan National High Magnetic Field Center, Huazhong University of Science and Technology, Wuhan, China.
⁵ Wuhan National High Magnetic Field Center, Huazhong University of Science and Technology, Wuhan, China. Electronic address: xthan@mail.hust.edu.cn.
⁶ Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: Zhling312@163.com.
⁷ Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: wpxiang2010@hust.edu.cn.

PMID: 37393821
DOI: 10.1016/j.ecoenv.2023.115186

Abstract

Rotenone, an insecticide that inhibits mitochondrial complex I and generates oxidative stress, is responsible for neurological disorders and affects the female reproductive system. However, the underlying mechanism is not fully understood. Melatonin, a potential free-radical scavenger, has been shown to protect the reproductive system from oxidative damage. In this study, we investigated the impact of rotenone on mouse oocyte quality and evaluated the protective effect of melatonin on oocytes exposed to rotenone. Our results showed that rotenone impaired mouse oocyte maturation and early embryo cleavage. However, melatonin prevented these negative effects by ameliorating rotenone-induced mitochondrial dysfunction and dynamic imbalance, intracellular Ca²⁺ homeostasis damage, ER stress, early apoptosis, meiotic spindle formation disruption, and aneuploidy in oocytes. Additionally, RNA sequencing analysis showed that rotenone exposure changed the expression of multiple genes involved in histone methylation and acetylation modifications that result in mouse meiotic defects. However, melatonin partially rescued these defects. These findings suggest that melatonin has protective effects against rotenone-induced mouse oocyte defects.

Keywords: ER stress; Histone modification; Melatonin; Mitochondrial dysfunction; Rotenone.