School of Nursing, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
MOE (Ministry of Education) Key Lab of Environment and Health, Department of Occupational and Environmental Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Department of Epidemiology and Health Statistics, School of Public Health, Medical College, Wuhan University of Science and Technology, Wuhan, 430030, China.
Environ Pollut. 2018 Dec;243(Pt A):693-702. doi: 10.1016/j.envpol.2018.09.030. Epub 2018 Sep 11.
BPA and NP are both typical endocrine disruptors, the exposed populations are widespread, and the health risks mustn't be ignored. However, the interactions between them on spermatogenesis are rarely mentioned. And the underlying mechanism is unclear yet. In the present study, prepubertal SD rats were exposed to different low doses of BPA and NP separately or jointly for 4 weeks. The results indicate that the joint exposure induced excessive apoptosis and autophagy in the testes, as proved by a series of characteristics such as chromatin condensation and autophagosomes formation. Besides, endocrine disorders and oxidative stress were also caused by the exposure. Apoptosis was mediated by the mitochondrial apoptosis pathway, since the Bax and Caspase-3 gene expressions significantly increased with a prominent decrease of Bcl-2. While autophagy was caused by the inhibition of the Akt/mTOR pathway, as the expressions of the downstream genes Beclin-1, Atg5, Atg12 and the split of LC3 protein increased altogether. Worse yet, autophagy and apoptosis might reinforce each other and make the situation more severe in the joint group. What's more, remarkable histopathological changes such as spermatogenic epithelium atrophy, germ cell loss, and various ultrastructural modifications were strongly related to the apoptosis and autophagy. In aggregate, this study shows the enormous risk on male reproductive system brought by the interactions between BPA and NP. The findings provide a broader vision to understand the roles of apoptosis and autophagy induced by the joint exposure in the aggravation of spermatogenesis impairment, which could be a reference for the situation of complex EDCs exposure-induced male reproductive toxicity, and possibly inspire us to find new ideas for preventive and therapeutic treatments.
双酚 A（BPA）和壬基酚（NP）均为典型的内分泌干扰物，暴露人群广泛，其健康风险不容忽视。然而，它们在生殖方面的相互作用却很少被提及，其潜在机制尚不清楚。在本研究中，将未成年 SD 大鼠分别或联合暴露于不同低剂量的 BPA 和 NP 中 4 周。结果表明，联合暴露会导致睾丸中过度的细胞凋亡和自噬，这一系列特征如染色质浓缩和自噬体形成均可证明。此外，还会引起内分泌失调和氧化应激。凋亡是由线粒体凋亡途径介导的，因为 Bax 和 Caspase-3 基因表达显著增加，而 Bcl-2 明显减少。而自噬是由 Akt/mTOR 通路的抑制引起的，因为下游基因 Beclin-1、Atg5、Atg12 的表达增加，同时 LC3 蛋白发生分裂。更糟糕的是，自噬和凋亡可能相互加强，使联合组的情况更加严重。此外，明显的组织病理学变化，如生精上皮萎缩、生殖细胞丢失和各种超微结构改变，与细胞凋亡和自噬密切相关。总之，这项研究表明 BPA 和 NP 之间的相互作用对男性生殖系统存在巨大风险。这些发现为理解联合暴露诱导的细胞凋亡和自噬在加剧生精功能障碍中的作用提供了更广阔的视角，可为复杂内分泌干扰物暴露引起的男性生殖毒性的情况提供参考，并可能为预防和治疗提供新的思路。
