Metabolomics reveals that ferroptosis participates in bisphenol A-induced testicular injury
Ling Kan Chi,
Qing Yuan,
Min Yan Wang,
Chun Rong Guo,
Xian Dan Zhu,
Hua Bo Jiang,
Qin Hua Zhang,
Yuan Zhao,
Li Li,
Hua Yan
Affiliations
Ling Kan Chi
Reproductive Medicine Center, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
Qing Yuan
Department of Gynecology, Department of Fetal Medicine and Prenatal Diagnosis Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 201203, China
Min Yan Wang
Department of Pathology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
Chun Rong Guo
Teaching Experimental Center, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
Xian Dan Zhu
Laboratory Animal Center, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
Hua Bo Jiang
Department of Gynecology, Department of Fetal Medicine and Prenatal Diagnosis Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, 201203, China
Qin Hua Zhang
Reproductive Medicine Center, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China
Yuan Zhao
Laboratory Animal Center, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Corresponding author.
Li Li
Reproductive Medicine Center, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Corresponding author.
Hua Yan
Reproductive Medicine Center, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China; Corresponding author.
Objective: Bisphenol A (BPA) is a common environmental endocrine disruptor that negatively impairs male reproductive ability. This study aimed to explore the alterations in serum metabolomics that occur following BPA exposure and the mechanism via which BPA induces the death of testicular cells in a male mouse model. Methods: The mice were classified into two groups: BPA-exposed and control groups, and samples were collected for metabolomic determination, semen quality analysis, electron microscopy, enzyme-linked immunosorbent assay, quantitative real-time PCR, pathological staining, and Western blot analysis. Results: BPA exposure caused testicular damage and significantly decreased sperm quality in mice. Combined with non-target metabolomic analysis, this was closely related to ferroptosis induced by abnormal metabolites of arachidonic acid and phosphatidylcholine, and the expression of its related genes, acyl CoA synthetase 4, glutathione peroxidase 4, lysophosphatidylcholine acyltransferase 3, and phosphatidylethanolamine-binding protein 1 were altered. Conclusion: BPA induced ferroptosis, caused testicular damage, and reduced fertility by affecting lipid metabolism in male mice. Inhibiting ferroptosis may potentially function as a therapeutic strategy to mitigate the male reproductive toxicity induced by BPA.
