Perfluorooctanesulfonic acid exposure altered hypothalamic metabolism and disturbed male fecundity
Perfluorooctanesulfonic acid exposure altered hypothalamic metabolism and disturbed male fecundity
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DOI：
10.1016/j.scitotenv.2022.156881
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发表时间：
2022-07-06
影响因子：
9.8
通讯作者：
Li, Lei
中科院分区：
文献类型：
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作者：
Li, Zijie;Lin, Ziyi;Li, Lei
以前的研究已经检查了全氟辛烷磺酸（PFOS）对破坏血睾丸屏障和精子发生的影响。支持细胞和间质细胞受到干扰，导致睾丸激素水平和精子数量下降。然而，全氟辛烷磺酸对男性生殖力的影响并不局限于睾丸。在本研究中，我们证明了口服全氟辛烷磺酸（1 μ g/g体重和5 μ g/g体重）会降低促黄体生成素(LH)/促黄体生成素受体（LHr）的功能，并降低附睾精子活力。睾丸转录组分析一致显示，全氟辛烷磺酸改变了与精子活力和甾体生成相关的一组基因的表达。在暴露于PFOS的小鼠中，c-Fos免疫染色显示与焦虑样行为相关的侧隔核（LS）、室旁丘脑（PVT）、蓝斑（LC）活化。下丘脑的代谢组学分析显示，暴露于全氟辛烷磺酸会扰乱蛋白质的翻译，以及神经递质和神经调节剂的生物合成。综上所述，全氟辛烷磺酸暴露导致的脑核激活、下丘脑代谢组的移位和LH/LHr回路的减少表明该毒物对男性生殖的系统性影响。
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 dem-onstrated that oral PFOS exposure (1 mu g/g BW and 5 mu g/g BW) decreased the function of the Luteinizing hormone (LH)/Luteinizing hormone receptor (LHr) and decreased epididymal sperm motility. Consistently, testicular tran-scriptome 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.