Polystyrene nanoplastics promote CHIP-mediated degradation of tight junction proteins by activating IRE1α/XBP1s pathway in mouse Sertoli cells

Abstract

Microplastics (MPs) and nanoplastics (NPs) widely exist in human living environment and enter the body through water, food chain and breathing. Several studies have shown that MPs or NPs disrupt the blood-testis barrier in rodents. However, the molecular mechanism by which MPs and NPs damage the blood-testis barrier remains unclear. In the present study, our aim was to investigate the molecular mechanism of the destruction of blood-testis barrier induced by polystyrene (PS)-NPs. Mice were treated with 50 μg/kg·day PS-NPs by tail vein injection once daily for two consecutive days. The results showed that PS-NPs exposure significantly decreased the levels of tight junction (TJ) proteins ZO-2, occludin and claudin-11 in testis of mice. In vitro, we used TM4 Sertoli cells to explore the underlying mechanism of the decrease in TJ proteins induced by PS-NPs. We found that PS-NPs activated IRE1α and induced its downstream XBP1 splicing, which in turn elevated the expression of the E3 ubiquitin ligase CHIP, then CHIP triggers proteasomal degradation of ZO-2, occludin, and claudin-11 proteins. Our findings suggest that IRE1α/XBP1s/CHIP pathway is a pivotal mechanism of TJ proteins degradation induced by PS-NPs in mouse Sertoli cells. In conclusion, our results reveal that the degradation of TJ proteins is one of the mechanisms of blood-testis barrier destruction caused by acute exposure to PS-NPs.

Keywords

• Nanoplastics
• ER stress
• Blood-testis barrier
• Protein degradation
• Ubiquitin ligase