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22 July 2021 Heat stress induces oxidative stress and activates the KEAP1-NFE2L2-ARE pathway in bovine endometrial epithelial cells
Hirona Murata, Hiroki Kunii, Kazuya Kusama, Toshihiro Sakurai, Hanako Bai, Manabu Kawahara, Masashi Takahashi
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Abstract

Heat stress adversely affects the reproductive function in cows. Although a relationship between heat stress and oxidative stress has been suggested, it has not been sufficiently verified in bovine endometrial epithelial cells. Here, we investigated whether oxidative stress is induced by heat stress in bovine endometrial epithelial cells under high temperature. Luciferase reporter assays showed that the reporter activity of heat shock element and antioxidant responsive element was increased in endometrial epithelial cells cultured under high temperature compared to that in cells cultured under basal (thermoneutral) temperature. Also, nuclear factor, erythroid 2 like 2 (NFE2L2), a master regulator of cellular environmental stress response, stabilized and the expression levels of antioxidant enzyme genes increased under high temperature. Immunostaining confirmed the nuclear localization of NFE2L2 in endometrial epithelial cells cultured under high temperature. Quantitative polymerase chain reaction analysis showed that the expression levels of representative inflammatory cytokine genes, such as prostaglandin-endoperoxide synthase 2 (PTGS2) and interleukin 8, were significantly decreased in endometrial epithelial cells cultured under high temperature compared to those in cells cultured under basal temperature. Thus, our results suggest that heat stress induces oxidative stress, whereas NFE2L2 plays a protective role in bovine endometrial epithelial cells cultured under heat stress conditions.

Summary sentence

Heat stress induces oxidative stress, whereas NFE2L2, a master regulator of the cellular environmental stress response, has a protective role in bovine endometrial epithelial cells cultured under heat stress conditions.

Graphical Abstract

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© The Author(s) 2021. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Hirona Murata, Hiroki Kunii, Kazuya Kusama, Toshihiro Sakurai, Hanako Bai, Manabu Kawahara, and Masashi Takahashi "Heat stress induces oxidative stress and activates the KEAP1-NFE2L2-ARE pathway in bovine endometrial epithelial cells," Biology of Reproduction 105(5), 1114-1125, (22 July 2021). https://doi.org/10.1093/biolre/ioab143
Received: 12 March 2021; Accepted: 19 July 2021; Published: 22 July 2021
KEYWORDS
bovine uterus
endometrial epithelial cells
heat stress
oxidative stress
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