Abstract
A high concentration of Zearalenone (ZEA) will perturb the differentiation of germ cells, and induce a death of germ cells, but the toxic mechanism and molecular mechanism remain unclear. The Sertoli cells (SCs) play an irreplaceable role in spermatogenesis. In order to explore the potential mechanism of ZEA male reproductive toxicity, we studied the effects of ZEA on cell proliferation, cell-cycle distribution, cell-cycle-related proteins and autophagy-related pathway the PI3K/Akt/mTOR signaling in primary cultured rats SCs, and the effects of autophagy and PI3K/AKT/m TOR signaling pathway on the SCs cell-cycle arrest induced by ZEA treated with the autophagy promoter RAPA, autophagy inhibitor CQ, and the PI3K inhibitor LY294002, respectively. The data revealed that ZEA could inhibit the proliferation of SCs by arresting the cell cycle in the G2/M phase and trigger the autophagy via inhibiting the PI3K/Akt/m TOR signaling pathway. Promoting or inhibiting the level of autophagy could either augment or reverse the arrest of cell cycle. And it was regulated by PI3K/Akt/m TOR signaling pathway. Taken together, this study provides evidence that autophagy and PI3K/Akt/m TOR signaling pathway are involved in regulating rats primary SCs cell-cycle arrest due to ZEA in vitro. To some extent, ZEA-induced autophagy plays a protective role in this process.
Highlights
Zearalenone (ZEA), which has always been called F-2 toxin, is synthesized by the polyketide pathway, a serious mycotoxin existed in human food and animal feed [1,2]
TOR/m TOR (** p < 0.01), while the expression of LC3II/LC3I was significantly increased (** p < 0.01). These results suggested that PI3K/Akt/mTOR signaling pathway exerted a negative regulatory role in autophagy which ZEA induced in SCs
Toxins 2018, 10, 398(** p < 0.01). These results suggested that PI3K/Akt/mTOR signaling pathway exerted a7 of 14 negative regulatory role in autophagy which ZEA induced in SCs
Summary
Zearalenone (ZEA), which has always been called F-2 toxin, is synthesized by the polyketide pathway, a serious mycotoxin existed in human food and animal feed [1,2]. Many studies have shown that ZEA and its dangerous secondary fungal metabolite can induce reproductive toxicity, immunotoxicity, DNA damage, and carcinogenicity qualities [3,4]. Toxins 2018, 10, 398 are more sensitive to ZEA compared to male animals, so studies of ZEA have mainly concentrated on its toxicity in the female endocrine system [5,6]. Studies have shown that ZEA has estrogenic activity that acts on the reproductive system of animals by binding to estrogen receptors and results in a variety of estrogenic effects [8,9]. Qing [11] showed that ZEA can significantly reduce testosterone secretion in Leydig cells by the cAMP pathway in both luteinizing hormone and human chorionic gonadotropin environments
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