{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:21:53Z","timestamp":1790709713239,"version":"4.1.0"},"reference-count":67,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,12,18]],"date-time":"2022-12-18T00:00:00Z","timestamp":1671321600000},"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":["Birth Defects Research"],"published-print":{"date-parts":[[2023,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Tramadol hydrochloride or tramadol is an opioid analgesic that acts on the central nervous system. The pregnancy category of tramadol is determined as \u201cC\u201d according to the Food and Drug Administration. There are no adequate and well\u2010controlled studies in pregnant women. In this study, we aimed to reveal the effects of tramadol on neural tube (midline) closure by analyzing morphologically, histologically and genetically in chick embryos.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Ninety White Leghorn species, fertile and 0\u2010day\u2010old specific pathogen\u2010free eggs (60\u2009\u00b1\u20095\u00a0g) were used in the study. Eggs were divided into a total of six groups (control, sham, and drug groups). Four different doses of tramadol (1, 2.5, 5, and 7.5\u00a0mg\/egg) were administered subblastodermically at the 28th hour of the incubation. All eggs were opened at the 48th hour of incubation and evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Embryos in the control group according to Hamburger\u2013Hamilton classification were compatible with stages 13 and 14. In the groups treated with tramadol, it was determined that the embryos had neural tube closure defects (such as neck, tail regions) and some embryos showed developmental retardation due to the increase in the drug dose. In the statistical analysis performed, a significant difference was found between the control group and the group receiving the highest dose of tramadol in terms of crown\u2010rump length and number of somites (<jats:italic>p<\/jats:italic>\u00a0&lt;\u2009.05). The brain and reproductive expression gene expression was upregulated in embryos at each of tramadol doses compared to control group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>It was determined that tramadol causes neural tube closure defects in embryos depending on the dose.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdr2.2137","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T02:44:00Z","timestamp":1671417840000},"page":"1079-1092","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Effect of tramadol hydrochloride on neural tube development in 48\u2010hr chick embryos: Argyrophilic nucleolar organizing region and genetic analysis study"],"prefix":"10.1002","volume":"115","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2378-1183","authenticated-orcid":false,"given":"Emre","family":"Atay","sequence":"first","affiliation":[{"name":"Department of Anatomy, Faculty of Medicine Afyonkarahisar Health Sciences University Afyonkarahisar Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1853-7098","authenticated-orcid":false,"given":"Erhan","family":"Bozkurt","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Faculty of Medicine Afyonkarahisar Health Sciences University Afyonkarahisar Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9947-9917","authenticated-orcid":false,"given":"Ay\u015fe","family":"Ertekin","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Faculty of Medicine Afyonkarahisar Health Sciences University Afyonkarahisar Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchemneu.2018.10.002"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23100"},{"issue":"2","key":"e_1_2_8_4_1","doi-asserted-by":"crossref","first-page":"216","DOI":"10.26496\/bjz.2010.171","article-title":"The development of chicken cerebellar cortex and the determination of AgNOR activity of the Purkinje cell nuclei","volume":"140","author":"Akar S.","year":"2010","journal-title":"Belgian Journal of Zoology"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1791"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/1743-8454-3-6"},{"key":"e_1_2_8_7_1","volume-title":"Drugs in pregnancy and lactation 7th edition: A reference guide to fetal and neonatal risk","author":"Briggs G.","year":"2005"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1366-0071(99)80019-9"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210733"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0067896"},{"key":"e_1_2_8_11_1","volume-title":"Global report on birth defects: The hidden toll of dying and disabled children","author":"Christianson A.","year":"2006"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-013-0963-y"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1177\/0960327114531994"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2643"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70110-8"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2003.015917"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1006\/excr.1995.1228"},{"key":"e_1_2_8_18_1","volume-title":"StatPearls.","author":"Dhesi M.","year":"2021"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(03)00424-6"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.2147\/IJN.S72337"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD003726.pub4"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2008.03102.x"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1929"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.5603\/FM.a2018.0080"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.4149\/BLL_2016_126"},{"key":"e_1_2_8_26_1","unstructured":"Food and Drug Administration. 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