Is toxicant-induced Sertoli cell injury in vitro a useful model to study molecular mechanisms in spermatogenesis?

Abstract

Sertoli cells isolated from rodents or humans and cultured in vitro are known to establish a functional tight junction (TJ)-permeability barrier that mimics the blood-testis barrier (BTB) in vivo. This model has been widely used by investigators to study the biology of the TJ and the BTB. Studies have shown that environmental toxicants (e.g., perfluorooctanesulfonate (PFOS), bisphenol A (BPA) and cadmium) that exert their disruptive effects to induce Sertoli cell injury using this in vitro model are reproducible in studies in vivo. Thus, this in vitro system provides a convenient approach to probe the molecular mechanism(s) underlying toxicant-induced testis injury but also to provide new insights in understanding spermatogenesis, such as the biology of cell adhesion, spermatid transport, and others. Herein, we provide a brief and critical review based on studies using this in vitro model of Sertoli cell cultures using primary cells isolated from rodent testes versus humans to monitor environmental toxicant-mediated Sertoli cell injury, and this information is relevant to the molecular mechanisms that regulate spermatogenesis. In short, recent findings have shown that environmental toxicants exert their effects on Sertoli cells to induce testis injury through their action on Sertoli cell actin- and/or microtubule-based cytoskeleton. These effects are mediated via their disruptive effects on actin- and/or microtubule-binding proteins. Sertoli cells also utilize differential spatiotemporal expression of these actin binding proteins to confer plasticity to the BTB to regulate germ cell transport across the BTB.

Zika Virus Infects Human Sertoli Cells and Modulates the Integrity of the In Vitro Blood-Testis Barrier Model

“…In vitro SCB models comprised of human and mouse SCs have been used to study mechanisms of SC function in spermatogenesis and effects of environmental toxins on barrier integrity leading to male infertility (35,36). However, this study for the first time uses an in vitro model of the SCB to characterize virus transmigration kinetics and to understand the interactions of infected peritubular leukocytes with SCs.…”

Cadmium‐induced toxicity increases prolyl endopeptidase (PREP) expression in the rat testis

“…It has been demonstrated that subcutaneous or intraperitoneal administrations of Cd cause edema, inflammation, and hemorrhage in rat testis (Djuric et al, 2015; Nolan & Shaikh, 1986), leading to altered histology of the organ (Marettová, Maretta, & Legáth, 2015; Obianime & Roberts, 2009). Thus, all the cellular population of testicular tissue can be affected by Cd, including decrease in the number and aberrant morphology of spermatogonia and spermatocytes (Marettová et al, 2015), along with Sertoli cell actin and/or microtubule‐based cytoskeleton alterations (N. Li, Mruk, Lee, Wong, & Cheng, 2016; Xiao et al, 2014). Moreover, many studies have correlated Cd exposure to reduced male fertility, as shown by poor semen quality and decreased sperm count (Benoff, Jacob, & Hurley, 2000; de Angelis et al, 2017; De Franciscis et al, 2015; Y. Li, Wu, Zhou, & Gao, 2016; Pant, Kumar, Upadhyay, Gupta, & Chaturvedi, 2015).…”

Benzo[a]pyrene‐decreased gap junctional intercellular communication via calcium/calmodulin signaling increases apoptosis in TM4 cells

“…Therefore, BaP‐induced male reproductive toxicity merits further investigation. In the testes, spermatogenesis is a highly regulated process that includes germ cell multiplication and differentiation (Li, Mruk, Lee, Wong, & Cheng, ). Sertoli cells are the primary supporting cells that create the structural and physiological environment for spermatogenic cell development, and they provide a permissive milieu necessary for spermatogenesis (Cheng et al, ).…”