Altered m6A modification is involved YAP-mediated apoptosis response in 4-vinylcyclohexene diepoxide induced ovotoxicity

Yang Li; Meifang Li; Jian Liu; Guangning Nie; Hongyan Yang

doi:10.1016/j.ecoenv.2023.115192

Altered m6A modification is involved YAP-mediated apoptosis response in 4-vinylcyclohexene diepoxide induced ovotoxicity

Ecotoxicol Environ Saf. 2023 Jun 30:262:115192. doi: 10.1016/j.ecoenv.2023.115192. Online ahead of print.

Authors

Yang Li¹, Meifang Li², Jian Liu¹, Guangning Nie¹, Hongyan Yang³

Affiliations

¹ Department of Gynaecology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, China.
² Shanxi Provincial Hospital of Chinese Medicine, Taiyuan, Shanxi 030012, China.
³ Department of Gynaecology, The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510120, China; Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, Guangdong 510120, China. Electronic address: hongyanyang@gzucm.edu.cn.

PMID: 37393819
DOI: 10.1016/j.ecoenv.2023.115192

Abstract

4-Vinylcyclohexene diepoxide (VCD), an industrial occupational health hazard chemical associated with premature ovarian insufficiency (POI) and reproductive failure. Recently, investigators have paid an increasing attention on VCD model of menopause recapitulates the natural, physiological transition through perimenopause to menopause. The current study sought to examining the mechanisms of follicular loss and exploring the effect of the model on systems outside of the ovaries. In this study, 28 days female SD rats were injected with VCD (160 mg/kg) vehicle for 15 consecutive days, euthanized in the diestrus phase approximately 100 days after the onset of treatment. Reproductive system injury, Neuroendocrine, sex hormone levels and receptor were observed, the levels of N6-methyladenosine (m6A) RNA modification and the expression of modulator genes were first measured. The VCD treated rats showing irregular estrous cycles, significantly reduced in the number of primordial follicles, the preantral and antral follicles also decreased significantly, accompanied by the plasma level of FSH increased and anti-Mullerian hormone (AMH) were decreased. The total m6A level was significantly decreased after exposure to VCD. Moreover, ALKBH5-mediated YAP m6A modification changed in VCD - induced premature ovarian insufficiency. These present work provides a new perspective on m6A modification in the VCD-induced POI rat model, which could provide valuable insights into the mechanisms underlying follicle development and finding new therapeutic targets for follicle prematurely exhausted. Also provide novel methodological guidance and endocrine basis to guide research and extend the applications in premature ovarian insufficiency model.

Keywords: ALKBH5; Environmental exposure; N6-methyladenosine; Premature ovarian insufficiency Model; VCD; YAP.