Mechanistic Insights into PFOS-Mediated Sertoli Cell Injury

Abstract

Studies have proven that per- and polyfluoroalkyl substances are harmful to humans, most notably perfluorooctanesulfonate (PFOS). PFOS induces rapid disorganization of actin- and microtubule (MT)-based cytoskeletons in primary cultures of rodent and human Sertoli cells, perturbing Sertoli cell gap junction communication, thereby prohibiting Sertoli cells from maintaining cellular homeostasis in the seminiferous epithelium to support spermatogenesis. PFOS perturbs several signaling proteins/pathways, such as FAK and mTORC1/rpS6/Akt1/2. The use of either an activator of Akt1/2 or overexpression of a phosphomimetic (and constitutively active) mutant of FAK or connexin 43 has demonstrated that such treatment blocks PFOS-induced Sertoli cell injury by preventing actin- and MT-based cytoskeletal disorganization. These findings thus illustrate an approach to manage PFOS-induced reproductive dysfunction.

Keywords: FAK; PFOS; Sertoli cell injury; actin; cytoskeleton; environmental toxicant; human Sertoli cell; mTORC1; microtubule; rpS6; testis.