Abstract Title:

Excessive apoptosis and defective autophagy contribute to developmental testicular toxicity induced by fluoride.

Abstract Source:

Environ Pollut. 2016 Jan 31 ;212:97-104. Epub 2016 Jan 31. PMID: 26840522

Abstract Author(s):

Shun Zhang, Qiang Niu, Hui Gao, Rulin Ma, Rongrong Lei, Cheng Zhang, Tao Xia, Pei Li, Chunyan Xu, Chao Wang, Jingwen Chen, Lixing Dong, Qian Zhao, Aiguo Wang

Article Affiliation:

Shun Zhang

Abstract:

Fluoride, a ubiquitous environmental contaminant, is known to impair testicular functions and fertility; however the underlying mechanisms remain obscure. In this study, we used a rat model to mimic human exposure and sought to investigate the roles of apoptosis and autophagy in testicular toxicity of fluoride. Sprague-Dawley rats were developmentally exposed to 25, 50, or 100 mg/L sodium fluoride (NaF) via drinking water from pre-pregnancy to post-puberty, and then the testes of offspring were excised on postnatal day 56. Our results demonstrated that developmental NaF exposure induced an enhanced testicular apoptosis, as manifested by a series of hallmarks such as caspase-3 activation, chromatin condensation and DNA fragmentation. Further study revealed that fluoride exposure elicited significant elevations in the levels of cell surface death receptor Fas with a parallel increase in cytoplasmic cytochrome c, indicating the involvement of both extrinsic and intrinsic apoptotic pathways. Intriguingly, fluoride treatment also simultaneously increased the number of autophagosomes and the levels of autophagy marker LC3-II but not Beclin1. Unexpectedly, the expression of p62, a substrate that is degraded by autophagy, was also significantly elevated, suggestingthat the accumulated autophagosomes resulted from impaired autophagy degradation rather than increased formation. Importantly, these were associated with marked histopathological lesions including spermatogenic failure and germ cell loss, along with severe ultrastructural abnormalities in testes. Taken together, our findings provide deeper insights into roles of excessive apoptosis and defective autophagy in the aggravation of testicular damage, which could contribute to a better understanding of fluoride-induced male reproductive toxicity.

Study Type : Animal Study

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Sayer Ji
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