{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T11:50:32Z","timestamp":1791805832373,"version":"4.3.4"},"reference-count":27,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T00:00:00Z","timestamp":1655856000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Reprod Domestic Animals"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cryptorchidism, as a common congenital disease of canine testes, is mainly caused by factors leading to endocrine abnormalities in testes and infertility in a heat stress and hypoxia microenvironment. Moreover, heat stress and hypoxia, as critical microenvironmental factors, promote epithelial\u2013mesenchymal transition (EMT), which occurs during adult tissue remodelling responses including carcinogenesis and fibrosis and is the main cause of testicular tumours. In this study, we found by haematoxylin\u2013eosin staining that the canine cryptorchid tissue produced a lot of collagen fibres. Also, the quantitative PCR and Western blot results showed that the mRNA and protein levels of the heat stress makers HSP70 and HO\u20101 and the hypoxia maker HIF\u20101\u03b1 are significant higher compared with normal testes. Moreover, we found the expression levels of TGF\u2010\u03b2s and its two receptors TGF\u2010\u03b2RI and TGF\u2010\u03b2RII increased in case of cryptorchidism. From the study in vitro, we found both heat stress and COCl<jats:sub>2<\/jats:sub> mimic hypoxia inhibited the secretion of testosterone (T) and androstenedione (A4) and promoted the expression of the EMT maker \u03b1\u2010SMA and vimentin in Leydig cells, and also that heat stress and COCl<jats:sub>2<\/jats:sub> stimulated with the TGF\u2010\u03b2 signalling promoted the expression of TGF\u2010\u03b2s and its two type receptors and also the active phosphorylation of Smad2 and Smad3. The use of LY2109761, a receptor inhibitor of TGF\u2010\u03b2s\/Smad signalling pathway, was associated with heat stress and COCl<jats:sub>2<\/jats:sub> suppression of androgens' secretion and stimulated EMT in Leydig cells. These findings characterized a novel pathogenesis of cryptorchidism and provided a new idea for therapeutics.<\/jats:p>","DOI":"10.1111\/rda.14174","type":"journal-article","created":{"date-parts":[[2022,6,9]],"date-time":"2022-06-09T12:19:34Z","timestamp":1654777174000},"page":"1046-1055","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Heat stress and hypoxia inhibit the secretion of androgens and induce epithelial\u2010to\u2010mesenchymal transition associated with activated <scp>TGF<\/scp>\u2010\u03b2\/Smad signalling in canine cryptorchidism"],"prefix":"10.1111","volume":"57","author":[{"given":"Zihui","family":"Wang","sequence":"first","affiliation":[{"name":"Animal Science and Technology College Beijing University of Agriculture  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"Animal Science and Technology 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