Exploration of intrinsic and extrinsic apoptotic pathways in zearalenone-treated rat sertoli cells

Abstract

Zearalenone (ZEA) is a nonsteroidal estrogenic mycotoxin produced mainly by Fusarium. ZEA causes reproductive disorders and is both cytotoxic and genotoxic in animals; however, little is known regarding the molecular mechanism(s) leading to ZEA toxicity. Sertoli cells are somatic cells that support the development of spermatogenic cells. The objective of this study was to explore the effects of ZEA on the proliferation, apoptosis, and necrosis of rat Sertoli cells to uncover signaling pathways underlying ZEA cytotoxicity. ZEA reduced the proliferation of rat Sertoli cells in a dose-dependent manner, as indicated by a CCK8 assay, while flow cytometry revealed that ZEA caused both apoptosis and necrosis. Immunoblotting revealed that ZEA treatment increased the ratio of Bax/Bcl-2, as well as the expression of FasL and caspases-3, -8, and -9, in a dose-dependent manner. Collectively, these data suggest that ZEA induced apoptosis and necrosis in rat Sertoli cells via extrinsic and intrinsic apoptotic pathways. This study provides new insights into the molecular mechanisms by which ZEA exhibits cytotoxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1731-1739, 2016.

The role of the Fas/FasL signaling pathway in environmental toxicant-induced testicular cell apoptosis: An update

“…These include supporting structural stability, providing nutrients and synthesizing other essential elements for germ cells, and constructing the blood-testis barrier (BTB) (Cheng and Mruk 2012). Therefore, any damage to Sertoli cells will severely impact spermatogenesis (Xu et al 2015). Sertoli cell apoptosis mainly involves FasL-dependent, direct or indirect regulation of the intrinsic and extrinsic apoptotic pathways (Xu et al 2015).…”

“…Therefore, any damage to Sertoli cells will severely impact spermatogenesis (Xu et al 2015). Sertoli cell apoptosis mainly involves FasL-dependent, direct or indirect regulation of the intrinsic and extrinsic apoptotic pathways (Xu et al 2015). On the one hand, FasL induces caspase-8 activation of the extrinsic apoptotic pathway, followed by activation of the caspase-3, −6, −7 cascade reaction, leading to cell apoptosis; on the other hand, activation of caspase-8 contributes to the Bax/Bcl-2 reaction of the intrinsic apoptosis pathway and initiates caspase-9, caspase-3 signal to induce apoptosis (Hengartner 2000).…”

Zearalenone Promotes Cell Proliferation or Causes Cell Death?

“…ZEA could induce cell apoptosis in porcine granulosa cells through the mitochondrial and caspase-dependent pathway [ 18 ]. ZEA could also affect the expressions of Bcl-2 family proteins including up-regulating Bax and down-regulating Bcl-2 expression [ 90 , 91 ].…”

Effect of high-fructose diet-induced metabolic syndrome on the pituitary-gonadal axis from adolescence through adulthood in male albino rats and the possible protective role of ginger extract. A biochemical, histological and immunohistochemical study

“…Robeva et al [64] have also reported, through clinical trials, that Sertoli cell function is suppressed in MetS. As Sertoli cells support and provide nutrition for the developing germ cells and are absolutely necessary for proper germ cell development and viability [55], Sertoli cell dysfunction reduces supportive capacity and impairs spermatogenesis and fertility [85]. Sertoli cell changes may also explain the abnormal presence of spermatids near the basement membrane as reported by Russell et al [65] who suggested spermatids' phagocytosis by Sertoli cells and, then, failure of release.…”