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Although a relationship between heat and oxidative stress has been suggested, the underlying mechanism has not been sufficiently examined in reproduction\u2010related cells. Therefore, we aimed to investigate whether heat stress induces oxidative stress using a variety of reproduction\u2010related cells including bovine placental and cumulus\u2013granulosa cells, human cell lines derived from cervical and endometrial cancers, and fibroblasts derived from endometrium. Quantitative polymerase chain reaction analysis showed that the expression levels of representative heat and oxidative stress\u2013related genes were significantly increased in cells cultured at high temperatures compared with those in cells cultured at basal temperatures. Moreover, luciferase reporter assays showed that the reporter activity of the heat shock element and antioxidant responsive element (ARE) was increased in cells cultured at high temperatures compared with that in cells cultured at basal temperatures. Furthermore, the stability of nuclear factor erythroid 2 like 2 (NFE2L2), a master regulator of the cellular stress response, increased under high temperatures. Point mutations in Kelch\u2010like ECH\u2010associated protein 1 (KEAP1) cysteine residues reduced the luciferase activity. Our results suggest that heat stress induces oxidative stress and that the KEAP1\u2010NFE2L2\u2010ARE pathway may play a protective role in reproduction\u2010related cells against heat stress.<\/jats:p>","DOI":"10.1111\/asj.70023","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T02:37:59Z","timestamp":1737945479000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Heat stress induces oxidative stress and activates the KEAP1\u2010NFE2L2\u2010ARE pathway in reproduction\u2010related cells"],"prefix":"10.1111","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9940-1880","authenticated-orcid":false,"given":"Hanako","family":"Bai","sequence":"first","affiliation":[{"name":"Laboratory of Animal Breeding and Reproduction, Research Faculty of Agriculture Hokkaido University  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Kawahara","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Breeding and Reproduction, Research Faculty of Agriculture Hokkaido University  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Kusama","sequence":"additional","affiliation":[{"name":"Department of Endocrine Pharmacology Tokyo University of Pharmacy and Life Sciences  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiro","family":"Sakurai","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science Ohu University  Koriyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"Pfarrer","sequence":"additional","affiliation":[{"name":"Institute for Anatomy University of Veterinary Medicine Hannover, Foundation Bischofsholer Damm  Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2448-915X","authenticated-orcid":false,"given":"Masashi","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Laboratory of Animal Breeding and Reproduction, Research Faculty of Agriculture Hokkaido University  Sapporo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,1,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-3-28"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.22316"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/asj.13474"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-018-2836-6"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.3168\/jds.S0022-0302(02)74296-3"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1401417"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.23123"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2008.112797"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2023.112000"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.theriogenology.2016.12.024"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1262\/jrd.2012-017"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.theriogenology.2005.06.011"},{"key":"e_1_2_7_14_1","first-page":"264","article-title":"Tissue culture studies of the proliferative capacity of cervical carcinoma and normal epithelium","volume":"12","author":"Gey G. 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