Effects of Bisphenol A on reproductive toxicity and gut microbiota dysbiosis in male rats

作者：Ruijing Liu, Dongbao Cai, Xusheng Li, Bo Liu, Jiali Chen, Xinwei Jiang, Haiwei Li, Zhenhua Li, Katja J. Teerds, Jianxia Sun, Weibin Bai, Yulong Jin · 发表于：Ecotoxicology and Environmental Safety · 年份：2022 · DOI：10.1016/j.ecoenv.2022.113623 · 被引用次数：60 · 研究领域：Effects and risks of endocrine disrupting chemicals、Immunotoxicology and immune responses

Bisphenol A (BPA) is an environmental endocrine disruptor. Recent studies have shown an association between decreased spermatogenesis and gut microbiota alteration. However, the potential associations and mechanisms of BPA exposure on spermatogenesis, hormone production, and gut microbiota remain unknown. This study aims to investigate BPA-induced male reproductive toxicity and the potential link with gut microbiota dysbiosis. Male Sprague Dawley rats were exposed to BPA at different doses by oral gavage for thirty consecutive days. The extent of testicular damage was evaluated by basic parameters of body weight and hematoxylin-eosin (H&E) staining. Next, we determined the mRNA levels and protein levels of apoptosis, histone-related factors, and mammalian target of rapamycin (mTOR) pathway in testes. Finally, 16 S rDNA sequencing was used to analyze gut microbiota composition after BPA exposure. BPA exposure damaged testicular histology, significantly decreased sperm count, and increased sperm abnormalities. In addition, BPA exposure caused oxidative stress and cell apoptosis in testes. The levels of histone (H2A, H3) were significantly increased, while ubiquitin histone H2A (ub-H2A) and ubiquitin histone H2B (ub-H2B) were markedly reduced. Furthermore, BPA activated the PI3K and AKT expression, but the protein expressions of mTOR and 4EBP1 in testes were inhibited significantly. Additionally, the relative abundance of class Gammaproteobacteria, and order Betaproteobacteriale...