Key Laboratory for Bio-Based Materials and Energy of Ministry of Education, College of Materials and Energy, South China Agricultural University, Guangzhou 510630, PR China.
Department of Food Science and Engineering, Institute of Food Safety and Nutrition, Guangdong Engineering Technology Center of Food Safety Molecular Rapid Detection, Jinan University, Guangzhou 510632, PR China.
Ecotoxicol Environ Saf. 2022 Jul 1;239:113623. doi: 10.1016/j.ecoenv.2022.113623. Epub 2022 May 11.
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 Betaproteobacteriales was significantly higher when treated with a high dose of BPA compared to the control group, which was negatively correlated with testosterone level. This study highlights the relationship between BPA-induced reproductive toxicity and gut microbiota disorder and provides new insights into the prevention and treatment of BPA-induced reproductive damage.
双酚 A（BPA）是一种环境内分泌干扰物。最近的研究表明，精子发生减少与肠道微生物群改变之间存在关联。然而，BPA 暴露对精子发生、激素产生和肠道微生物群的潜在关联和机制仍不清楚。本研究旨在探讨 BPA 诱导的雄性生殖毒性及其与肠道微生物群失调的潜在联系。雄性 Sprague Dawley 大鼠通过口服灌胃连续 30 天暴露于不同剂量的 BPA。通过体重和苏木精-伊红（H&E）染色的基本参数评估睾丸损伤程度。接下来，我们测定了睾丸中凋亡、组蛋白相关因子和哺乳动物雷帕霉素靶蛋白（mTOR）通路的 mRNA 水平和蛋白水平。最后，用 16S rDNA 测序分析 BPA 暴露后肠道微生物群的组成。BPA 暴露损伤睾丸组织学，显著降低精子计数，增加精子畸形。此外，BPA 暴露导致睾丸氧化应激和细胞凋亡。组蛋白（H2A、H3）水平显著升高，而泛素组蛋白 H2A（ub-H2A）和泛素组蛋白 H2B（ub-H2B）明显降低。此外，BPA 激活了 PI3K 和 AKT 的表达，但睾丸中 mTOR 和 4EBP1 的蛋白表达明显受到抑制。此外，与对照组相比，高剂量 BPA 处理时，类变形菌纲和β变形菌目相对丰度显著增加，与睾酮水平呈负相关。本研究强调了 BPA 诱导的生殖毒性与肠道微生物群紊乱之间的关系，并为预防和治疗 BPA 诱导的生殖损伤提供了新的见解。
