{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T11:51:20Z","timestamp":1791805880828,"version":"4.3.4"},"reference-count":45,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T00:00:00Z","timestamp":1660089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Foundation of Korea (NRF), Korean government (MIST)","award":["[2021R1G1A1091690]"],"award-info":[{"award-number":["[2021R1G1A1091690]"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cryptorchidism, a condition in which testes fail to descend from the abdomen into the scrotum, is a risk factor for infertility and germ cell cancer. Normally, tight junctions between adjacent Sertoli cells in the testes form a blood\u2013testes barrier that regulates spermatogenesis; however, the effect of cryptorchidism on tight junctions is not well-understood. We established a model of heat-induced testicular damage in dogs using surgical cryptorchidism. We sequenced RNA to investigate whether certain transcripts are expressed at higher rates in heat-damaged versus normally descended testes. Claudins, cell adhesion molecules, were relatively highly expressed in cryptorchid testes: claudins 2, 3, 5, 11, and 18 were significantly increased in cryptorchid testes and reduced by orchiopexy. SOX9-positive Sertoli cells were present in the seminiferous tubules in both cryptorchid and control testes. Using real-time PCR and Western blot analysis to compare Sertoli cells cultured at 34 \u00b0C and 37 \u00b0C, we found that Sertoli cell claudins 2, 3, 5, 11, and 18 were significantly increased at 37 \u00b0C; however, accumulation was higher in the G0\/G1 phase in Sertoli cells cultured at 34 \u00b0C. These results indicate that testicular hyperthermia caused by cryptorchidism affects claudin expression, regulated germ cell death, and the proliferation of Sertoli cells.<\/jats:p>","DOI":"10.3390\/cells11162476","type":"journal-article","created":{"date-parts":[[2022,8,10]],"date-time":"2022-08-10T04:20:32Z","timestamp":1660105232000},"page":"2476","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Transcriptomic Analysis of Testicular Gene Expression in a Dog Model of Experimentally Induced Cryptorchidism"],"prefix":"10.3390","volume":"11","author":[{"given":"Hyunjhung","family":"Jhun","sequence":"first","affiliation":[{"name":"Food Industry Infrastructure Team, Korea Food Research Institute, Wanju-gun 55365, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Won-Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Livestock, Korea National University of Agricultures and Fisheries, Jeonju-si 54874, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Ki","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Livestock, Korea National University of Agricultures and Fisheries, Jeonju-si 54874, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun-Goo","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Smart Life Science, College of Life and Environment Science, Sangji University, Wonju-si 26339, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4589-2052","authenticated-orcid":false,"given":"Hyun-Jung","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Animal Biotechnology, College of Life and Environment Science, Sangji University, Wonju-si 26339, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1093\/biolreprod\/3.3.308","article-title":"The blood-testis barrier in the rat and the physiological compartmentation of the seminiferous epithelium","volume":"3","author":"Dym","year":"1970","journal-title":"Biol. Reprod."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/S0074-7696(08)60397-6","article-title":"Sertoli cell junctions: Morphological and functional correlates","volume":"94","author":"Russell","year":"1985","journal-title":"Int. Rev. Cytol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/jemt.1070200104","article-title":"The blood-testis barrier and Sertoli cell junctions: Structural considerations","volume":"20","author":"Pelletier","year":"1992","journal-title":"Microsc. Res. Tech."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1083\/jcb.141.7.1539","article-title":"Claudin-1 and -2: Novel integral membrane proteins localizing at tight junctions with no sequence similarity to occludin","volume":"141","author":"Furuse","year":"1998","journal-title":"J. Cell Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1073\/pnas.96.2.511","article-title":"Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands","volume":"96","author":"Morita","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1083\/jcb.145.3.579","article-title":"Claudin-11\/OSP-based tight junctions of myelin sheaths in brain and Sertoli cells in testis","volume":"145","author":"Morita","year":"1999","journal-title":"J. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1159\/000200078","article-title":"Downstream genes of Sox8 that would affect adult male fertility","volume":"3","author":"Singh","year":"2009","journal-title":"Sex. Dev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1080\/01485010390204913","article-title":"Expression of claudin-1 in mouse testis","volume":"49","author":"Gye","year":"2003","journal-title":"Arch. Androl."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1096\/fj.06-070342","article-title":"Blood-testis barrier dynamics are regulated by testosterone and cytokines via their differential effects on the kinetics of protein endocytosis and recycling in Sertoli cells","volume":"22","author":"Yan","year":"2008","journal-title":"FASEB J."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"16696","DOI":"10.1073\/pnas.0506084102","article-title":"Androgens regulate the permeability of the blood-testis barrier","volume":"102","author":"Meng","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1111\/j.1365-2605.2009.00964.x","article-title":"Early effects of Sertoli cell-selective androgen receptor ablation on testicular gene expression: Early androgen action in Sertoli cells","volume":"33","author":"Willems","year":"2010","journal-title":"Int. J. Androl."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1016\/S0002-9440(10)65039-0","article-title":"Decreased expression of mouse Rbm3, a cold-shock protein, in Sertoli cells of cryptorchid testis","volume":"156","author":"Danno","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1974","DOI":"10.1093\/humrep\/det111","article-title":"International geographic correlation study of the prevalence of disorders of male reproductive health","volume":"28","author":"Serrano","year":"2013","journal-title":"Hum. Reprod."},{"key":"ref_14","first-page":"873","article-title":"Congenital defects of the dog","volume":"14","author":"Hoskins","year":"1992","journal-title":"Comp. Cont. Edu. Pract. Vet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.theriogenology.2011.08.030","article-title":"Plasma Insulin-like peptide 3 and testosterone concentrations in male dogs: Changes with age and effects of cryptorchidism","volume":"77","author":"Pathirana","year":"2012","journal-title":"Theriogenoelogy"},{"key":"ref_16","first-page":"677","article-title":"The evaluation of blood concentrations of testosterone, 17beta-oestradiol and anti-Mu llerian hormone in dogs with cryptorchidism and testicular tumours","volume":"20","author":"Hornakova","year":"2017","journal-title":"Pol. J. Vet. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1111\/age.12977","article-title":"Altered expression of CYP17A1 and CYP19A1 in undescended testes of dogs with unilateral cryptorchidism","volume":"51","author":"Krzeminska","year":"2020","journal-title":"Anim. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1016\/S0015-0282(16)55999-8","article-title":"Increase in testicular temperature in case of cryptorchidism in boys","volume":"59","author":"Mieusset","year":"1993","journal-title":"Fertil. Steril."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.theriogenology.2007.04.025","article-title":"Common causes of male dog infertility","volume":"68","author":"Memon","year":"2007","journal-title":"Theriogenology"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.theriogenology.2020.08.034","article-title":"Amelioration of heat stress-induced damage to testes and sperm quality","volume":"158","author":"Shahat","year":"2020","journal-title":"Theriogenology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"257","DOI":"10.5625\/lar.2016.32.4.257","article-title":"Establishment of a surgically induced cryptorchidism canine recipient model for spermatogonial stem cell transplantation","volume":"32","author":"Lee","year":"2016","journal-title":"Lab. Anim. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6029271","DOI":"10.1155\/2016\/6029271","article-title":"Subculture of germ cell-derived colonies with GATA4-positive feeder cells from neonatal pig testes","volume":"2016","author":"Lee","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1007\/s11427-010-4072-7","article-title":"Molecular basis of cryptorchidism-induced infertility","volume":"53","author":"Liu","year":"2010","journal-title":"Sci. China Life Sci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1098\/rstb.2010.0025","article-title":"Claudin and occludin expression and function in the seminiferous epithelium","volume":"365","author":"Morrow","year":"2010","journal-title":"Philos. Trans. R. Soc. Lond. B Biol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"4268","DOI":"10.1091\/mbc.e08-12-1236","article-title":"Zona Occludens-2 is critical for blood-testis barrier integrity and male fertility","volume":"20","author":"Xu","year":"2009","journal-title":"Mol. Biol. Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3012","DOI":"10.1210\/endo.141.8.7625","article-title":"Developmental and hormonal regulation of the expression of oligodendrocyte-specific protein\/claudin 11 in mouse testis","volume":"141","author":"Hellani","year":"2000","journal-title":"Endocrinology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1489","DOI":"10.1210\/endo-129-3-1489","article-title":"Regulation of transepithelial electrical resistance in two-compartment Sertoli cell cultures: In vitro model of the blood-testis barrier","volume":"129","author":"Janecki","year":"1991","journal-title":"Endocrinology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1093\/molehr\/gay012","article-title":"In vitro formation of the blood\u2013testis barrier during long-term organotypic culture of human prepubertal tissue: Comparison with a large cohort of pre\/peripubertal boys","volume":"24","author":"Poels","year":"2018","journal-title":"Mol. Hum. Reprod."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"182","DOI":"10.3389\/fendo.2018.00182","article-title":"Anti-M\u00fcllerian hormone and testicular function in prepubertal boys with cryptorchidism","volume":"9","author":"Grinspon","year":"2018","journal-title":"Front. Endocrinol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1136\/vr.102611","article-title":"Anti-M\u00fcllerian hormone: A potential biomarker for differential diagnosis of cryptorchidism in dogs","volume":"175","author":"Gharagozlou","year":"2014","journal-title":"Vet. Rec."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.18632\/oncotarget.2936","article-title":"Claudin-1 enhances tumor proliferation and metastasis by regulating cell anoikis in gastric cancer","volume":"6","author":"Huang","year":"2015","journal-title":"Oncotarget"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1562","DOI":"10.1007\/s10620-012-2043-5","article-title":"Down-regulation of claudin-3 is associated with proliferative potential in early gastric cancers","volume":"57","author":"Okugawa","year":"2012","journal-title":"Dig. Dis. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1038\/labinvest.2011.117","article-title":"Claudin-4 overexpression is associated with epigenetic derepression in gastric carcinoma","volume":"91","author":"Kwon","year":"2011","journal-title":"Lab. Investig."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3109\/07357907.2010.512594","article-title":"Claudin-6, 7, or 9 Overexpression in the human gastric adenocarcinoma cell line AGS increases its invasiveness, migration, and proliferation rate","volume":"29","author":"Fortoul","year":"2011","journal-title":"Cancer Investig."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/s13046-018-0754-y","article-title":"Inactivation of the tight junction gene CLDN11 by aberrant hypermethylation modulates tubulins polymerization and promotes cell migration in nasopharyngeal carcinoma","volume":"37","author":"Li","year":"2018","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"96249","DOI":"10.18632\/oncotarget.21997","article-title":"Methylated claudin-11 associated with metastasis and poor survival of colorectal cancer","volume":"8","author":"Li","year":"2017","journal-title":"Oncotarget"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1007\/s00345-004-0398-8","article-title":"Clinical epidemiology of testicular germ cell tumors","volume":"22","author":"Dieckmann","year":"2004","journal-title":"World J. Urol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"32","DOI":"10.3389\/fendo.2013.00032","article-title":"Testicular cancer and cryptorchidism","volume":"4","author":"Ferguson","year":"2013","journal-title":"Front. Endocrinol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.theriogenology.2019.09.031","article-title":"Oxidative stress mediates heat-induced changes of tight junction proteins in porcine sertoli cells via inhibiting CaMKK\u03b2-AMPK pathway","volume":"142","author":"Yang","year":"2020","journal-title":"Theriogenology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1093\/molehr\/gaaa002","article-title":"Melatonin protects the mouse testis against heat-induced damage","volume":"26","author":"Zhang","year":"2020","journal-title":"Mol. Hum. Reprod."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1080\/10715760500130517","article-title":"Accelerated impairment of spermatogenic cells in SOD1-knockout mice under heat stress","volume":"39","author":"Ishii","year":"2005","journal-title":"Free Radic. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"461","DOI":"10.2478\/s11535-014-0287-0","article-title":"Oxidative stress regulates expression of claudin-1 in human RPE cells","volume":"9","author":"Hirata","year":"2014","journal-title":"Open Life Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"21421","DOI":"10.1074\/jbc.M115.654913","article-title":"Mitochondrial respiratory dysfunction induces claudin-1 expression via reactive oxygen species-mediated heat shock factor 1 activation, leading to hepatoma cell invasiveness","volume":"290","author":"Lee","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_44","first-page":"306","article-title":"Radiation-induced oxidative stress and claudin-11 mRNA expression in the testis","volume":"19","author":"Zhang","year":"2013","journal-title":"Zhonghua Nan Ke Xue"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1111\/j.1365-2605.2010.01089.x","article-title":"Scrotal heat stress causes a transient alteration in tight junctions and induction of TGF-\u03b2 expression","volume":"34","author":"Cai","year":"2011","journal-title":"Int. J. Androl."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/16\/2476\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:06:35Z","timestamp":1760141195000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/11\/16\/2476"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,10]]},"references-count":45,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["cells11162476"],"URL":"https:\/\/doi.org\/10.3390\/cells11162476","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,10]]}}}