Croucher Institute for Environmental Sciences, Department of Biology, Hong Kong Baptist University, Hong Kong SAR 999077, China; The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518000, China.
The Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518000, China.
Sci Total Environ. 2022 Oct 20;844:156881. doi: 10.1016/j.scitotenv.2022.156881. Epub 2022 Jun 23.
Previous studies have examined the effects of perfluorooctanesulfonic acid (PFOS) on disruption of the blood-testis barrier and spermatogenesis. Sertoli and Leydig cells were perturbed, resulting in a decrease in testosterone levels and sperm counts. However, the effects of PFOS on male fecundity are not limited to the testes. In this study, we demonstrated that oral PFOS exposure (1 μg/g BW and 5 μg/g BW) decreased the function of the Luteinizing hormone (LH)/Luteinizing hormone receptor (LHr) and decreased epididymal sperm motility. Consistently, testicular transcriptome analysis revealed that PFOS altered the expression of a cluster of genes associated with sperm motility and steroidogenesis. In mice exposed to PFOS, c-Fos immunostaining showed activation of the lateral septal nucleus (LS), paraventricular thalamus (PVT), locus coeruleus (LC), which are known to be related to anxiety-like behaviors. Metabolomic analyses of the hypothalamus revealed that exposure to PFOS perturbed the translation of proteins, as well as the biosynthesis of neurotransmitters and neuromodulators. Altogether, the activation of brain nuclei, shift of hypothalamic metabolome, and reduction of LH/LHr circuit resulted from PFOS exposure suggested the toxicant's systematic effects on male reproduction.
先前的研究已经考察了全氟辛烷磺酸 (PFOS) 对血睾屏障和精子发生破坏的影响。支持细胞和间质细胞受到干扰,导致睾酮水平和精子计数下降。然而,PFOS 对雄性生育力的影响不仅限于睾丸。在这项研究中,我们证明了口服 PFOS 暴露(1μg/g BW 和 5μg/g BW)降低了促黄体生成素 (LH)/促黄体生成素受体 (LHr) 的功能,并降低了附睾精子的运动能力。一致地,睾丸转录组分析显示 PFOS 改变了与精子运动和类固醇生成相关的一簇基因的表达。在 PFOS 暴露的小鼠中,c-Fos 免疫染色显示侧隔核(LS)、室旁丘脑(PVT)和蓝斑(LC)的激活,已知这些核与焦虑样行为有关。下丘脑的代谢组学分析显示,PFOS 暴露扰乱了蛋白质的翻译以及神经递质和神经调质的生物合成。总之,PFOS 暴露引起的脑核激活、下丘脑代谢组的变化以及 LH/LHr 回路的减少表明该毒物对雄性生殖系统的系统影响。