Abstract
Although it has been reported that perinatal, especially prenatal exposure to polybrominated diphenyl ethers (PBDEs) alters offspring's fertility, but little is known regarding their longitudinal effects over time. In the current study, we determined the associations between prenatal exposure to 2,2',4,4',5-pentabromodiphenyl ether (PBDE-99) of environmentally relevant levels in pregnant ICR mice and spermatogenic impairments in male offspring on postnatal day 70. Then, we monitored functional injuries in spermatogenic cells (GC-1 spg) exposed to PBDE-99 in vitro. Furthermore, transcriptome sequencing and bioinformatic analysis were used to investigate the underlying mechanism of PBDE-99 exposure to GC-1 spg. Additionally, the expression levels of key genes in the relevant pathways were quantified. Our findings indicated that exposure to PBDE-99 caused significantly spermatogenic injuries, which partly owing to the accumulation of reactive oxygen species, dysregulation of autophagy, and finally induced spermatogenic cell apoptosis. Rescue validation experiments showed that stimulating autophagy could alleviate spermatogenic cell injury induced by PBDE-99. In conclusion, our findings indicated that the dysfunction of autophagy played a significant role in long-term reproductive toxicity following prenatal exposure to environmental concentrations of PBDE-99.