Abstract
PFOS (perfluorooctanesulfonate, or perfluorooctane sulfonic acid) is an anthropogenic fluorosurfactant widely used in consumer products. While its use in Europe, Canada and the U.S. has been banned due to its human toxicity, it continues to be used in China and other developing countries as a global pollutant. Herein, using an in vitro model of Sertoli cell blood-testis barrier (BTB), PFOS was found to induce Sertoli cell injury by perturbing actin cytoskeleton through changes in the spatial expression of actin regulatory proteins. Specifically, PFOS caused mis-localization of Arp3 (actin-related protein 3, a branched actin polymerization protein) and palladin (an actin bundling protein). These disruptive changes thus led to a dis-organization of F-actin across Sertoli cell cytosol, causing truncation of actin microfilament, thereby failing to support the Sertoli cell morphology and adhesion protein complexes (e.g., occludin-ZO-1, CAR-ZO-1, and N-cadherin-ß-catenin), through a down-regulation of p-Akt1-S473 and p-Akt2-S474. The use of SC79, an Akt1/2 activator, was found to block the PFOS-induced Sertoli cell injury by rescuing the PFOS-induced F-actin dis-organization. These findings thus illustrate PFOS exerts its disruptive effects on Sertoli cell function downstream through Akt1/2. As such, PFOS-induced male reproductive dysfunction can possibly be managed through an intervention on Akt1/2 expression.
Highlights
PFOS is a global pollutant and an environmental toxicant, widely used as a fabric protector, serving as a stain repellant in drapery, carpets and clothing
PFOS perturbs TJ- and basal ES-protein localization in Sertoli cells – an involvement of p-Akt1/2? Sertoli cells isolated from 20-day-old rat testes were cultured in vitro for 3 days to form a cell epithelium with an established functional TJ-barrier, which mimicked the Sertoli cell blood-testis barrier (BTB) in vivo[19,20,21,22]
This in vitro-based system has been widely used by investigators to study BTB dynamics[23,24,25,26,27,28,29], and many of the findings were subsequently confirmed by studies in vivo[30,31,32,33]
Summary
PFOS is a global pollutant and an environmental toxicant, widely used as a fabric protector, serving as a stain repellant in drapery, carpets and clothing. Studies in rodents have generally supported the notion that PFOS perturbs testis function, such as by inducing Sertoli cell injury and disrupting Leydig cell steroidogenic function[9,10,11,12]. In order to better understand the signaling pathway of FAK-mediated rescue function during PFOS-induced Sertoli cell injury, we sought to examine the involvement of Akt in PFOS-mediated Sertoli cell injury, and its functional relationship with p-FAK-Y407. This mechanistic study provides additional insight on the molecular mechanism by which PFOS causes reproductive dysfunction in males through its disruptive effects on the Sertoli cell of the mammalian testis
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