Real-life exposure to Fusarium toxins deoxynivalenol and zearalenone triggers apoptosis and activates NLRP3 inflammasome in bovine primary theca cells

Abstract

Cattle are deemed less susceptible to mycotoxins due to the limited internal exposure resulting from rumen microbiota activity. However, the signi cant amounts of Fusarium mycotoxins deoxynivalenol (DON) and zearalenone (ZEN) frequently detected in bovine follicular uid samples suggest that they could affect ovarian function.Both mycotoxins trigger several patterns of cell death and activate the NLRP3 in ammasome in the intestine. In vitro studies have reported a number of adverse effects on bovine oocytes. However, the biological relevance of such ndings with regard to realistic concentrations of DON and ZEN in bovine follicular uid is still not clear. Hence, it is important to better characterize the effects of dietary exposure to DON and ZEN on the bovine ovary.Using bovine primary theca cells, this study investigated the effects of real-life patterns for bovine ovary exposure to DON and ZEN, but also DON metabolite DOM-1, on cell death and NLRP3 in ammasome activation.Exposure to DON starting from 0.1µM signi cantly decreased theca cell viability. The kinetics of phosphatidylserine translocation and loss of membrane integrity showed that ZEN and DON, but not DOM-1, induce an apoptotic phenotype. qPCR analysis of the expression of NLRP3, PYCARD, IL-1β, IL-18, and GSDMD in primary theca cells at concentrations of mycotoxin previously reported in cow follicular uid clearly indicated that DON and DOM-1 individually and in mixture, but not ZEN, activate NLRP3 in ammasome.Altogether, these results suggest that current European Union guidance values for DON may not protect the bovine ovary from in ammatory disorders.