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全氟辛烷磺酸暴露改变了下丘脑的代谢,扰乱了雄性的生育能力。

Perfluorooctanesulfonic acid exposure altered hypothalamic metabolism and disturbed male fecundity.

机构信息

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.

出版信息

Sci Total Environ. 2022 Oct 20;844:156881. doi: 10.1016/j.scitotenv.2022.156881. Epub 2022 Jun 23.

DOI:10.1016/j.scitotenv.2022.156881
PMID:35753445
Abstract

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.

摘要

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。

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引用本文的文献

1
PFOS-elicited metabolic perturbation in liver and fatty acid metabolites in testis of adult mice.全氟辛烷磺酸(PFOS)引起成年小鼠肝脏代谢紊乱和睾丸脂肪酸代谢物变化。
Front Endocrinol (Lausanne). 2023 Nov 22;14:1302965. doi: 10.3389/fendo.2023.1302965. eCollection 2023.
2
Toxic effects of per- and polyfluoroalkyl substances on sperm: Epidemiological and experimental evidence.全氟和多氟烷基物质对精子的毒性作用:流行病学和实验证据。
Front Endocrinol (Lausanne). 2023 Feb 20;14:1114463. doi: 10.3389/fendo.2023.1114463. eCollection 2023.