Perfluorooctane sulfonate induces suppression of testosterone biosynthesis via Sertoli cell-derived exosomal/miR-9-3p downregulating StAR expression in Leydig cells. (15th May 2022)

• Record Type: Journal Article
• Authors: Huang, Jiyan; Ren, Hang; Chen, Anni; Li, Ting; Wang, Hongxia; Jiang, Lianlian; Zheng, Shaokai; Qi, Han; Ji, Binyan; Wang, Xipei; Qu, Jianhua; Zhao, Jianya; Qiu, Lianglin
• Is Part Of: Environmental pollution. Volume 301(2022)
• Publication Date: 2022-05-15
• Subjects: Perfluorooctane sulfonate -- Leydig cell -- Sertoli cell -- microRNA-9-3p -- Testosterone -- Steroidogenic acute regulatory protein; PFOS perfluorooctane sulfonate -- StAR steroidogenic acute regulatory protein -- miRNA microRNA -- SC-Exo exosomes isolated from the cell supernatant of Sertoli cells -- SC-Exo (PFOS-0 μM) exosomes isolated from the cell supernatant of Sertoli cells which were treated with 0 μM of PFOS -- SC-Exo (PFOS-15 μM) exosomes isolated from the cell supernatant of Sertoli cells which were treated with 15 μM of PFOS -- SC-Exo (PFOS-30 μM) exosomes isolated from the cell supernatant of Sertoli cells which were treated with 30 μM of PFOS -- SC-Exo (GW4869) exosomes isolated from the cell supernatant of Sertoli cells which were treated with 10 μM of GW4869 -- SC-Exo (PFOS-30 μM + GW4869) exosomes isolated from the cell supernatant of Sertoli cells which were treated with 30 μM of PFOS and 10 μM of GW4869; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2022.118960
• Languages: English
• ISSNs: 0269-7491

Abstract

Abstract: 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. Graphical abstract: Image 1 Highlights: PFOS inhibits testosterone biosynthesis in vivo and in vitro . PFOS increases miR-9-3p in Sertoli cells and Sertoli cell-derived exosomes (SC-Exo). SC-Exo mediates the transfer of miR-9-3p from Sertoli cells to Leydig cells. miR-9-3p directly regulates StAR expression in Leydig cells. PFOS inhibits testosterone biosynthesis via SC-Exo/miR-9-3p/StAR signaling pathway.