Wu Jun, Deng Fuming, Tang Xiangliang, Chen Wenbin, Zhou Rui, Zhao Tianxin, Mao Xiangming, Shu Fangpeng
Department of Urology, Guangzhou Women and Children's Medical Center, National Children's Medical Center for South Central Region, Guangzhou Medical University, Guangzhou, Guangdong, China; Department of Urology, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China.
Department of Urology, Guangzhou Women and Children's Medical Center, National Children's Medical Center for South Central Region, Guangzhou Medical University, Guangzhou, Guangdong, China.
J Hazard Mater. 2023 Jun 15;452:131234. doi: 10.1016/j.jhazmat.2023.131234. Epub 2023 Mar 20.
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.
尽管已有报道称围产期，尤其是产前接触多溴二苯醚（PBDEs）会改变后代的生育能力，但关于其随时间的纵向影响却知之甚少。在本研究中，我们确定了怀孕的ICR小鼠产前接触环境相关水平的2,2',4,4',5-五溴二苯醚（PBDE-99）与出生后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，利用转录组测序和生物信息学分析来研究PBDE-99暴露于GC-1 spg的潜在机制。另外，对相关途径中关键基因的表达水平进行了定量分析。我们的研究结果表明，暴露于PBDE-99会导致明显的生精损伤，这部分归因于活性氧的积累、自噬失调，最终诱导生精细胞凋亡。挽救验证实验表明，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重要作用。
