The mycotoxin metabolite deepoxydeoxynivalenol increases apoptosis and decreases steroidogenesis in bovine ovarian theca cells
Por:
Guerrero-Netro H.M., Estienne A., Chorfi Y., Price C.A.
Publicada:
1 ene 2017
Resumen:
The mycotoxin deoxynivalenol (DON) has been shown to inhibit ovarian granulosa cell function in cattle in vitro, but it is not known whether DON or its metabolite deepoxy-DON (DOM-1) affects theca cell function. The objectives of this study were to determine the effects of DON and of DOM-1 on theca cell steroidogenesis and apoptosis, and to determine the main pathways through which they act. Bovine theca cells were cultured in a nonluteinizing serum-free culture system, and challenged with DON or DOM-1 for 4 days to measure steroidogenesis and apoptosis, for 1-8 h to measure immediate-early genes, and for 5-60 min to measure phosphorylation of intracellular signaling proteins. Addition of DON decreased progesterone secretion at doses as low as 0.5 ng/ml but had no effect on testosterone secretion. Addition of DOM-1 inhibited progesterone and testosterone secretion at 0.5 ng/ml. Treatment of cells with 1 ng/ml DOM-1 increased the proportion of apoptotic cells, whereas DON had no effect. Addition of DON or DOM-1 stimulated phosphorylation of EIF2AK2,MAPK3/1, and AKT. However, DON inhibited and DOM-1 stimulatedMAPK14 phosphorylation. DON increased the levels of mRNA encoding early-immediate genes EGR1, EGR3, and FOS, whereas DOM-1 was without effect. DOM-1 but not DON increased abundance of mRNA of the endoplasmic reticulum (ER) stress-related proteins, PRKRA and ATF4.We conclude that DOM-1 has a major impact on theca function in cattle, and possibly induces theca cell apoptosis through ER stress. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction.
Filiaciones:
Guerrero-Netro H.M.:
Centre de recherche en reproduction et fertilit é, Faculté de médecine vét érinaire, Université de Montr éal, St-Hyacinthe, QU, Canada
Estienne A.:
Centre de recherche en reproduction et fertilit é, Faculté de médecine vét érinaire, Université de Montr éal, St-Hyacinthe, QU, Canada
Chorfi Y.:
Centre de recherche en reproduction et fertilit é, Faculté de médecine vét érinaire, Université de Montr éal, St-Hyacinthe, QU, Canada
Price C.A.:
Centre de recherche en reproduction et fertilit é, Faculté de médecine vét érinaire, Université de Montr éal, St-Hyacinthe, QU, Canada
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