Bisphenol A induces testicular oxidative stress in mice leading to ferroptosis.

Li LI; Min-yan Wang; Hua-bo Jiang; Chun-rong Guo; Xian-dan Zhu; Xia-qin Yao; Wei-wei Zeng; Yuan Zhao; Ling-kan Chi

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Bisphenol A induces testicular oxidative stress in mice leading to ferroptosis.

Author: Li LI ¹ ; Min-Yan WANG ² ; Hua-Bo JIANG ³ ; Chun-Rong GUO ⁴ ; Xian-Dan ZHU ⁵ ; Xia-Qin YAO ⁶ ; Wei-Wei ZENG ⁷ ; Yuan ZHAO ⁵ ; Ling-Kan CHI ¹
Author Information

1. Reproductive Medicine Center, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
2. Department of Pathology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
3. Shanghai Key Laboratory of Maternal Fetal Medicine, Department of Fetal Medicine and Prenatal Diagnosis Center, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 201203, China.
4. Teaching Experimental Center, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
5. Laboratory Animal Center, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
6. Department of Obstetrics, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201203, China.
7. Department of Gynecology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Publication Type:Journal Article
Keywords: bisphenol A; ferroptosis; mitochondrial damage; oxidative stress; testicular toxicity
MeSH: Male; Mice; Animals; Testis/metabolism*; Ferroptosis; Semen; Oxidative Stress
From: Asian Journal of Andrology 2023;25(3):375-381
CountryChina
Language:English
Abstract: 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.