Urban fine particulate matter (PM2.5) exposure destroys blood–testis barrier (BTB) integrity through excessive ROS-mediated autophagy

Abstract

Context: Blood–testis barrier (BTB), constituted by tight junctions (TJs), adherens junctions and gap junctions, is important for spermatogenesis. PM2.5 is known to impair testicular functions and reproduction. However, its effects on BTB and the underlying mechanisms remain obscure.

Objective: To investigate the roles of autophagy in BTB toxicity induced by PM2.5.

Materials and methods: Sprague–Dawley rats were developmentally exposed to normal saline (NS) or PM2.5 with the doses of 9 mg/kg b.w. and 24 mg/kg b.w. via intratracheal instillation for seven weeks. Success rate of mating, sperm quality, testicular morphology, expressions of BTB junction proteins and autophagy-related proteins were detected. In addition, expressions of oxidative stress markers were also analyzed.

Results: Our results demonstrated that developmental PM2.5 exposure induced noticeable decreased fertility, significantly reduced sperm count, increased sperm abnormality rate and severe testicular damage in histomorphology. The expressions of TJ (such as ZO-1 and occludin), gap junction (such as connexin43) were down-regulated significantly after PM2.5 treatment. Intriguingly, PM2.5 simultaneously increased the number of autophagosomes and the levels of autophagy marker LC3-II and p62, suggesting that the accumulated autophagosomes resulted from impaired autophagy degradation. Moreover, the expressions of HO-1 levels remarkably increased and expression levels of Gpx and SOD were significantly decreased after PM2.5 exposure. Vitamins E and C could alleviate the PM2.5-induced oxidative stress, reverse the autophagy defect and restore the BTB impairment.

Conclusions: Taken together, the results suggest that PM2.5 exposure destroys BTB integrity through excessive ROS-mediated autophagy. Our finding could contribute to a better understanding of PM2.5-induced male reproductive toxicity.

Keywords:

• PM2.5
• BTB
• oxidative stress
• autophagy

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Ethics statement

All experiments involving animals were approved by the Ethics Committee of Chongqing Medical University (license numbers: SCXK[YU]20110016).

Disclosure statement

The authors declare that they have no competing interests.

Additional information

Funding

This study is supported by National Natural Science Foundation of China [No. 81571425], Scientific and Technological Research Program of Chongqing Municipal Education Commission [KJ1600229], and Postgraduate Scientific Research Innovation Project of Chongqing Medical University [CYB16105].