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13 October 2017 The mycotoxin metabolite deepoxy-deoxynivalenol increases apoptosis and decreases steroidogenesis in bovine ovarian theca cells
Hilda M. Guerrero-Netro, Anthony Estienne, Younès Chorfi, Christopher A. Price
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Abstract

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.

Summary Sentence

Deepoxy-deoxynivalenol acts through EIF2AK2 to increase theca cell apoptosis and decrease steroid secretion.

© The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. For permissions, please e-mail: journals.permissions@oup.com
Hilda M. Guerrero-Netro, Anthony Estienne, Younès Chorfi, and Christopher A. Price "The mycotoxin metabolite deepoxy-deoxynivalenol increases apoptosis and decreases steroidogenesis in bovine ovarian theca cells," Biology of Reproduction 97(5), 746-757, (13 October 2017). https://doi.org/10.1093/biolre/iox127
Received: 23 January 2017; Accepted: 12 October 2017; Published: 13 October 2017
JOURNAL ARTICLE
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KEYWORDS
Apoptosis
follicle
ovary
ruminants
theca cells
toxicology
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