{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T16:43:42Z","timestamp":1772988222937,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2018,6,5]],"date-time":"2018-06-05T00:00:00Z","timestamp":1528156800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2018,6,5]],"date-time":"2018-06-05T00:00:00Z","timestamp":1528156800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"},{"start":{"date-parts":[[2018,6,5]],"date-time":"2018-06-05T00:00:00Z","timestamp":1528156800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2018,4,13]],"date-time":"2018-04-13T00:00:00Z","timestamp":1523577600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["clinicalkey.jp","clinicalkey.com","clinicalkey.es","clinicalkey.com.au","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["The Kaohsiung J of Med Scie"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      This study aims to explore the role of PERK\u2010eIF2\u03b1 signaling pathway in fetal male rats with hypospadias induced by maternal exposure to di\u2010n\u2010butyl phthalate (DBP). DBP was used to treat pregnant SD rats by gastric intubation from gestation day (GD) 14\u201318 to construct a hypospadias rat model. The amount, weight, anogenital distance (AGD), and hypospadias incidence of rats were recorded and the genital tubercle (GT) of fetal male rats was collected on GD 19. Western blotting was performed to detect the expressions of PERK\u2010eIF2\u03b1 pathway\u2010 and autophagy\u2010related proteins, and cell apoptosis was detected using TUNEL method. Then, GT fibroblasts of fetal rats were obtained and transfected with PERK\u2010siRNA to detect cell apoptosis and autophagy in each transfected group. The incidence of hypospadias was 43.49% in fetal male rats induced by DBP. The fetal rats in DBP group presented the decreased birth weight and anogenital distance (AGD)\/body weight ratio than the Control group (all\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05). Further, p\u2010PERK, p\u2010eIF2\u03b1 and ATF4 protein expressions and the ratio of LC3\u2010II\/LC3\u2010I were greatly increased in the GTs of fetal rats, while apoptosis index (AI) and P62 protein expression were evidently decreased (all\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05). In addition, the apoptosis rate was increased in GT fibroblasts after transfection of PERK\u2010siRNA with the increased P62 and reduced LC3\u2010II\/LC3\u2010I ratio (all\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05). Activation of PERK\u2010eIF2\u03b1 signaling pathway can influence the GT development of fetal male rats with hypospadias induced by DBP through activation of autophagy and inhibition of apoptosis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1016\/j.kjms.2018.04.002","type":"journal-article","created":{"date-parts":[[2018,6,5]],"date-time":"2018-06-05T07:42:57Z","timestamp":1528184577000},"page":"487-493","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"title":["Role of PERK\u2010eIF2\u03b1 signaling pathway in fetal male rats with hypospadias induced by di\u2010n\u2010butyl phthalate"],"prefix":"10.1002","volume":"34","author":[{"given":"Zhang","family":"Zhao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guo\u2010Chang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,6,5]]},"reference":[{"key":"e_1_2_7_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-008-0533-5"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1515\/jpem.2011.379"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20673"},{"key":"e_1_2_7_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-002-0799-y"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.etp.2014.07.003"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfh169"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1210\/mend.14.7.0465"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1539\/joh.L8091"},{"key":"e_1_2_7_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb0910-823"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/pros.22658"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.2008.00866.x"},{"key":"e_1_2_7_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.152900"},{"key":"e_1_2_7_14_2","doi-asserted-by":"crossref","DOI":"10.1161\/JAHA.113.000238","article-title":"PERK\u2010eIF2alpha\u2010ATF4\u2010CHOP signaling contributes to TNFalpha\u2010induced vascular calcification","volume":"2","author":"Masuda M.","year":"2013","journal-title":"J Am Heart Assoc"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules180910146"},{"key":"e_1_2_7_16_2","doi-asserted-by":"crossref","DOI":"10.1155\/2010\/515136","article-title":"Cytokines in the progression of pancreatic beta\u2010cell dysfunction","volume":"2010","author":"Wang C.","year":"2010","journal-title":"Int J Endocrinol"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2010.153"},{"key":"e_1_2_7_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2007.01308.x"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-016-1246-1"},{"key":"e_1_2_7_20_2","article-title":"Revised guide for the care and use of laboratory animals available. American physiological society","volume":"39","author":"Bayne K.","year":"1996","journal-title":"Physiologist"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2016.02.016"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpedsurg.2015.08.046"},{"key":"e_1_2_7_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9926(200003)61:3<172::AID-TERA4>3.0.CO;2-B"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00846"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.00530"},{"key":"e_1_2_7_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.415224"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-59745-157-4_4"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2012.05.015"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.05.023"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1539\/joh.16-0089-OA"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.6A0214-097R"},{"key":"e_1_2_7_32_2","first-page":"113","article-title":"Apolipoprotein e\u2010deficient lipoproteins induce foam cell formation by activation of PERK\u2010EIF\u20102alpha signaling cascade","volume":"2","author":"Zhao Y.","year":"2010","journal-title":"J Bioanal Biomed"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401984"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2009.06.002"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1101902"},{"key":"e_1_2_7_36_2","article-title":"Regulation of autophagy via PERK\u2010eIF2alpha effectively relieve the radiation myelitis induced by iodine\u2010125","volume":"8","author":"Yang Z.","year":"2013","journal-title":"PLoS One"}],"container-title":["The Kaohsiung Journal of Medical Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1607551X17308276?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S1607551X17308276?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.kjms.2018.04.002","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1016\/j.kjms.2018.04.002","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1016\/j.kjms.2018.04.002","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T11:22:32Z","timestamp":1772968952000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1016\/j.kjms.2018.04.002"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,5]]},"references-count":35,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2018,9]]}},"alternative-id":["10.1016\/j.kjms.2018.04.002"],"URL":"https:\/\/doi.org\/10.1016\/j.kjms.2018.04.002","archive":["Portico"],"relation":{},"ISSN":["1607-551X","2410-8650"],"issn-type":[{"value":"1607-551X","type":"print"},{"value":"2410-8650","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Role of PERK-eIF2\u03b1 signaling pathway in fetal male rats with hypospadias induced by di-n-butyl phthalate","name":"articletitle","label":"Article Title"},{"value":"The Kaohsiung Journal of Medical Sciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.kjms.2018.04.002","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 Kaohsiung Medical University. Published by Elsevier Taiwan LLC.","name":"copyright","label":"Copyright"}]}}