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.

尽管据报道围产期，尤其是产前接触多溴联苯醚 (PBDEs) 会改变后代的生育能力，但关于其随时间的纵向影响知之甚少。在当前的研究中，我们确定了怀孕 ICR 小鼠产前暴露于环境相关水平的 2,2',4,4',5-五溴二苯醚 (PBDE-99) 与产后第 70 天雄性后代生精障碍之间的关联. 然后，我们监测了体外暴露于 PBDE-99 的生精细胞 (GC-1 spg) 的功能损伤。此外，转录组测序和生物信息学分析用于研究 PBDE-99 暴露于 GC-1 spg 的潜在机制。此外，量化了相关通路中关键基因的表达水平。我们的研究结果表明，暴露于 PBDE-99 会导致显着的生精损伤，部分原因是活性氧的积累、自噬失调，最终诱导生精细胞凋亡。拯救验证实验表明，刺激自噬可以减轻 PBDE-99 诱导的生精细胞损伤。总之，我们的研究结果表明，自噬功能障碍在产前暴露于环境浓度的 PBDE-99 后的长期生殖毒性中起着重要作用。拯救验证实验表明，刺激自噬可以减轻 PBDE-99 诱导的生精细胞损伤。总之，我们的研究结果表明，自噬功能障碍在产前暴露于环境浓度的 PBDE-99 后的长期生殖毒性中起着重要作用。拯救验证实验表明，刺激自噬可以减轻 PBDE-99 诱导的生精细胞损伤。总之，我们的研究结果表明，自噬功能障碍在产前暴露于环境浓度的 PBDE-99 后的长期生殖毒性中起着重要作用。