Bisphenol A Induces Autophagy and Apoptosis Concurrently Involving the Akt/mTOR Pathway in Testes of Pubertal SD Rats
Bisphenol A Induces Autophagy and Apoptosis Concurrently Involving the Akt/mTOR Pathway in Testes of Pubertal SD Rats
复制标题
双酚 A 诱导青春期 SD 大鼠睾丸中同时涉及 Akt/mTOR 通路的自噬和细胞凋亡
DOI：
10.1002/tox.22339
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发表时间：
2017-08-01
影响因子：
4.5
通讯作者：
Yang, Kedi
中科院分区：
文献类型：
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作者：
Quan, Chao;Wang, Can;Yang, Kedi
双酚A（BPA）是一种典型的内分泌干扰物，已被证实可引起男性生殖毒性。然而，这种效应的确切机制仍不清楚。青春期是生殖发育的关键时期，青少年更容易受到外源性物质的影响。本研究旨在探讨双酚A对青春期男性生殖毒性的作用机制。将大鼠暴露于0、2、10、50 mg kg-1 bw BPA，然后检测性激素水平、氧化应激和精液质量。采用HE染色、TUNEL法和透射电镜观察睾丸组织的形态学变化、细胞凋亡和自噬。通过RT-PCR、蛋白质印迹和免疫组织化学染色来测量相关基因和蛋白质的表达。结果表明，BPA暴露导致青春期雄性SD大鼠氧化应激和内分泌紊乱，引起睾丸细胞凋亡和自噬，最终损害精子发生。在此过程中，Akt通路被激活，mTOR通路被抑制。总之，BPA在青春期睾丸中同时诱导细胞凋亡和自噬，这为我们对BPA雄性生殖毒性的理解增加了新的层次。© 2016 Wiley Periodicals，Inc.环境毒理学32：1977-1989，2017。
Bisphenol A (BPA), a typical endocrine disrupting chemical (EDC), has been proven to cause male reproductive toxicity. However, the precise mechanisms of this effect are still unclear. Puberty is a crucial period of reproductive development, and adolescents are more susceptible to xenobiotics. This research was designed to explore the mechanism of BPA toxicity on pubertal male reproduction. Rats were exposed to 0, 2, 10, 50 mg kg−1 bw BPA, then the levels of sex hormones, oxidative stress, and semen quality were detected. HE staining, TUNEL assay and transmission electron microscopy were used to investigate the morphological changes, apoptosis, and autophagy in testes, respectively. Expressions of relevant genes and proteins were measured by RT‐PCR, western blotting, and immunohistochemical staining. The results indicated that BPA exposure led to oxidative stress and endocrine disorders in pubertal male SD rats, caused apoptosis and autophagy in testes, and then damaged spermatogenesis ultimately. The Akt pathway was activated and the mTOR pathway was inhibited in the process. Taken together, BPA induced apoptosis and autophagy concurrently in pubertal testes, and this added a new layer to our understanding on male reproductive toxicity of BPA. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1977–1989, 2017.