Embryonic 6:2 FTOH exposure causes reproductive toxicity by disrupting the formation of the blood-testis barrier in offspring mice

Abstract

Previous studies have revealed nephrotoxicity, hepatotoxicity, subchronic developmental and reproductive toxicity in rats exposed to fluorotelomer alcohol (FTOH). However, the effects of embryonic 6:2 FTOH exposure on the reproductive system of offspring mice remain unclear. The purpose of this study is to explore the reproductive toxic effects of embryonic 6:2 FTOH exposure on offspring male mice and the related molecular mechanisms. Therefore, the pregnant mice were given corn oil or 6:2 FTOH by gavage from gestational days 12.5–21.5. The results demonstrated that embryonic 6:2 FTOH exposure resulted in disrupted testicular structure, low expression of tight junction protein between Sertoli cells (SCs), impaired blood-testis barrier (BTB) formation and maturation, reduced sperm viability and increased malformation, and induced testicular inflammation in the offspring of mice. Further in vitro studies showed that 6:2 FTOH treatment upregulated MMP-8 expression by activating AKT/NF-κB signaling pathway, which in turn enhanced occludin cleavage leading to the disruption of SCs barrier integrity. In summary, this study demonstrated that 6:2 FTOH exposure caused reproductive dysfunction in male offspring through disruption of BTB, which provided new insights into the effects of 6:2 FTOH exposure on the offspring.