期刊
ENVIRONMENTAL POLLUTION
卷 301, 期 -, 页码 -出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.envpol.2022.118960
关键词
Perfluorooctane sulfonate; Leydig cell; Sertoli cell; microRNA-9-3p; Testosterone; Steroidogenic acute regulatory protein
资金
- National Natural Science Foundation of China [81302452]
- Major Projects of Natural Sciences of University in Jiangsu Province of China [18KJB330004]
- Basic Scientific Research program of Nantong City [JC2019021, JC2020032]
- Scientific Research Starting Foundation for The Doctoral researcher of Nantong University [14B14]
The study investigated the mechanisms underlying the impact of PFOS on testosterone biosynthesis using in vivo and in vitro models. The findings suggest that PFOS can reduce testosterone secretion and reproductive hormone levels, with involvement of SC-Exo and miR-9-3p in this process.
Perfluorooctane sulfonate (PFOS) is associated with male reproductive disorder, but the related mechanisms are still unclear. In this study, we used in vivo and in vitro models to explore the role of Sertoli cell-derived exosomes (SC-Exo)/miR-9-3p/StAR signaling pathway on PFOS-induced suppression of testosterone biosynthesis. Forty male ICR mice were orally administrated PFOS (0.5-10 mg/kg/bw) for 4 weeks. Bodyweight, organ index, sperm count, reproductive hormones were evaluated. Primary Sertoli cells and Leydig cells were used to delineate the molecular mechanisms that mediate the effects of PFOS on testosterone biosynthesis. Our results demonstrated that PFOS dose-dependently induced a decrease in sperm count, low levels of testosterone, and damage in testicular interstitium morphology. In vitro models, PFOS significantly increased miR-9-3p levels in Sertoli cells and SC-Exo, accompanied by a decrease in testosterone secretion and StAR expression in Leydig cells when Leydig cells were exposed to SC-Exo. Meanwhile, inhibition of SC-Exo or miR-9-3p by their inhibitors significantly rescued PFOS-induced decreases in testosterone secretion and the mRNA and protein expression of the StAR gene in Leydig cells. In summary, the present study highlights the role of the SC-Exo/miR-9-3p/StAR signaling pathway in PFOS-induced suppression of testosterone biosynthesis, advancing our understanding of molecular mechanisms for PFOS-induced male reproductive disorders.
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