Open AccessBisphenol A induces testicular oxidative stress in mice leading to ferroptosis
Author(s) -
Yuan Zhao,
Ling-Kan Chi,
Li Li,
Minyan Wang,
Huabo Jiang,
Chao Guo,
Xiandan Zhu,
Xia-Qin Yao,
Weiwei Zeng
Publication year - 2022
Publication title -
asian journal of andrology/asian journal of andrology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 74
eISSN - 1745-7262
pISSN - 1008-682X
DOI - 10.4103/aja202266
Subject(s) - oxidative stress , andrology , sperm , malondialdehyde , ferritin , superoxide dismutase , bisphenol a , biology , bisphenol , gpx4 , endocrinology , endocrine disruptor , reproductive toxicity , medicine , chemistry , glutathione peroxidase , toxicity , hormone , endocrine system , biochemistry , organic chemistry , epoxy
Bisphenol A is a common environmental factor and endocrine disruptor that exerts a negative impact on male reproductive ability. By exploring bisphenol A-induced testicular cell death using the Institute of Cancer Research (ICR) mouse model, we found that a ferroptosis phenomenon may exist. Mice were divided into six groups and administered different doses of bisphenol A via intragastric gavage once daily for 45 consecutive days. Serum was then collected to determine the levels of superoxide dismutase and malondialdehyde. Epididymal sperm was also collected for semen analysis, and testicular tissue was collected for ferritin content determination, electron microscope observation of mitochondrial morphology, immunohistochemistry, real-time quantitative polymerase chain reaction, and western blot analysis. Exposure to bisphenol A was found to decrease sperm quality and cause oxidative damage, iron accumulation, and mitochondrial damage in the testes of mice. In addition, bisphenol A was confirmed to affect the expression of the ferroptosis-related genes, glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), cyclooxygenase 2 (COX2), and acyl-CoA synthetase 4 (ACSL4) in mouse testicular tissues. Accordingly, we speculate that bisphenol A induces oxidative stress, which leads to the ferroptosis of testicular cells. Overall, the inhibition of ferroptosis may be a potential strategy to reduce male reproductive toxicity caused by bisphenol A.