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Responses to cadmium toxicity were investigated using spermatocytes overexpressing p50ATF6, ATF4, and spliced XBP1s, belonging to the 3 unfolded protein response pathways. The ER stress and apoptosis response to cadmium were most strongly stimulated through the activating transcription factor 6 (ATF6) pathway; in contrast, siRNA-induced inhibition of protein expression could reduce apoptosis under stressful conditions. An in vivo experiment using mice confirmed that upregulation of p50ATF6 in the testis increased apoptosis in response to cadmium exposure. Further, when confirming the correlation between ER stress and MAPK in cadmium toxicity, p38 MAPK phosphorylation was strongly regulated by p50ATF6; p-p38 also mediated the activity of p50ATF6. Overall, these findings suggest that modulating the activity of p38 MAPK and p50ATF6 in cadmium exposure-induced toxicity can be considered a potential strategy to treat infertility.<\/jats:p>","DOI":"10.1093\/toxsci\/kfad055","type":"journal-article","created":{"date-parts":[[2023,5,31]],"date-time":"2023-05-31T15:43:52Z","timestamp":1685547832000},"page":"167-177","source":"Crossref","is-referenced-by-count":8,"title":["ATF6 is a critical regulator of cadmium-mediated apoptosis in spermatocytes"],"prefix":"10.1093","volume":"194","author":[{"given":"Sung Woo","family":"Lee","sequence":"first","affiliation":[{"name":"School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University , Daegu 41566, Republic of Korea"},{"name":"School of Life Sciences & Biotechnology, College of Natural Sciences, Kyungpook National University , Daegu 41566, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bokyung","family":"Kim","sequence":"additional","affiliation":[{"name":"School of Life Sciences & Biotechnology, College of Natural Sciences, Kyungpook National University , Daegu 41566, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Bae","family":"Seong","sequence":"additional","affiliation":[{"name":"National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB) , Cheongju 28116, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Ho","family":"Park","sequence":"additional","affiliation":[{"name":"Futuristic Animal Resource & Research Center (FARRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB) , Cheongju 28116, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong Jun","family":"Lee","sequence":"additional","affiliation":[{"name":"College of Medicine and Medical Research Institute, Chungbuk National University , Cheongju 28644, Republic of Korea"},{"name":"Research Institute, huMetaCELL Inc. , Gyeonggi-do , Bucheon 14786, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7106-1615","authenticated-orcid":false,"given":"Dong-Seok","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University , Daegu 41566, Republic of Korea"},{"name":"School of Life Sciences & Biotechnology, College of Natural Sciences, Kyungpook National University , Daegu 41566, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,6,1]]},"reference":[{"key":"2023072808474036800_kfad055-B1","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.reprotox.2007.10.004","article-title":"Effect of vitamins C and E on spermatogenesis in mice exposed to cadmium","volume":"25","author":"Acharya","year":"2008","journal-title":"Reprod. 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