{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T14:55:32Z","timestamp":1791644132704,"version":"4.3.4"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,11,23]],"date-time":"2023-11-23T00:00:00Z","timestamp":1700697600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2019A1515011889"],"award-info":[{"award-number":["2019A1515011889"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003453","name":"Natural Science Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2022A1515012107"],"award-info":[{"award-number":["2022A1515012107"]}],"id":[{"id":"10.13039\/501100003453","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    As a synthetic androgen, 17\u03b1\u2010methyltestosterone (MT) is widely used in aquaculture to induce sex reversal and may pose a potential risk to aquatic organisms. This ecological risk has attracted the attention of many scholars, but it is not comprehensive enough. Thus, the adverse effects of MT on zebrafish (\n                    <jats:italic>Danio rerio<\/jats:italic>\n                    ) were comprehensively evaluated from gonadal histology, as well as the mRNA expression levels of 47 genes related to hypothalamic\u2010pituitary\u2010gonadal (HPG) axis, germ cell differentiation, sex determination, and hypothalamus\u2010pituitary\u2010thyroid (HPT) axis. Adult zebrafish with a female\/male ratio of 5:7 were exposed to a solvent control (0.001% dimethyl sulfoxide) and three measured concentrations of MT (5, 51 and 583\u2009ng\/L) for 50\u2009days. The results showed that MT had no significant histological effects on the ovaries of females, but the frequency of late\u2010mature oocytes (LMO) showed a downward trend, indicating that MT could induce ovarian suppression to a certain extent. The transcriptional expression of activating transcription factor 4b1 (\n                    <jats:italic>atf4b1<\/jats:italic>\n                    ), activating transcription factor 4b2 (\n                    <jats:italic>atf4b2<\/jats:italic>\n                    ), calcium\/calmodulin\u2010dependent protein kinase II delta 1 (\n                    <jats:italic>camk2d1<\/jats:italic>\n                    ), calcium\/calmodulin\u2010dependent protein kinase II delta 2 (\n                    <jats:italic>camk2d2<\/jats:italic>\n                    ) and calcium\/calmodulin\u2010dependent protein kinase II inhibitor 2 (\n                    <jats:italic>camk2n2<\/jats:italic>\n                    ) genes in the brain of females increased significantly at all treatment groups of MT, and the mRNA expression of forkhead box L2a (\n                    <jats:italic>foxl2<\/jats:italic>\n                    ) and ovarian cytochrome P450 aromatase (\n                    <jats:italic>cyp19a1a<\/jats:italic>\n                    ) genes in the ovaries were down\u2010regulated by 5 and 583\u2009ng\/L group, which would translate into inhibition of oocyte development. As compared to females, MT had relatively little effects on the reproductive system of males, and only the transcriptional alterations of synaptonemal complex protein 3 (\n                    <jats:italic>sycp3<\/jats:italic>\n                    ) and 17\u2010alpha\u2010hydroxylase\/17,20\u2010lyase (\n                    <jats:italic>cyp17<\/jats:italic>\n                    ) genes were observed in the testes, not enough to affect testicular histology. In addition, MT at all treatments strongly increased corticotropin\u2010releasing hormone (\n                    <jats:italic>crh<\/jats:italic>\n                    ) transcript in the brain of females, as well as deiodinase 2 (\n                    <jats:italic>dio2<\/jats:italic>\n                    ) transcript in the brain of males. The paired box protein 8 (\n                    <jats:italic>pax8<\/jats:italic>\n                    ) gene was significantly decreased at 51 or 583\u2009ng\/L of MT in both female and male brains. The above results suggest that MT can pose potential adverse effects on the reproductive and thyroid endocrine system of fish.\n                  <\/jats:p>","DOI":"10.1002\/tox.24044","type":"journal-article","created":{"date-parts":[[2023,11,24]],"date-time":"2023-11-24T19:07:56Z","timestamp":1700852876000},"page":"1494-1504","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The effects of 17\u03b1\u2010methyltestosterone on gonadal histology and gene expression along hypothalamic\u2010pituitary\u2010gonadal axis, germ cells, sex determination, and hypothalamus\u2010pituitary\u2010thyroid axis in zebrafish (\n                    <i>Danio rerio<\/i>\n                    )"],"prefix":"10.1002","volume":"39","author":[{"given":"Minchun","family":"Li","sequence":"first","affiliation":[{"name":"Faculty of Chemistry and Environmental Science Guangdong Ocean University  Zhanjiang People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2845-4787","authenticated-orcid":false,"given":"Ning","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Fishery Guangdong Ocean University  Zhanjiang People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiting","family":"Huang","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Environmental Science Guangdong Ocean University  Zhanjiang People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang\u2010Gui","family":"Pan","sequence":"additional","affiliation":[{"name":"Guangxi Laboratory on the Study of Coral Reefs in the South China Sea Guangxi University  Nanning People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7898-5223","authenticated-orcid":false,"given":"Zhongdian","family":"Dong","sequence":"additional","affiliation":[{"name":"College of Fishery Guangdong Ocean University  Zhanjiang People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhong","family":"Lin","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Environmental Science Guangdong Ocean University  Zhanjiang People's Republic of China"},{"name":"Shenzhen Institute of Guangdong Ocean University  Shenzhen People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengyong","family":"Li","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Environmental Science Guangdong Ocean University  Zhanjiang People's Republic of China"},{"name":"Shenzhen Institute of Guangdong Ocean University  Shenzhen People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu\u2010Xia","family":"Jiang","sequence":"additional","affiliation":[{"name":"South China Institute of Environmental Sciences Ministry of Ecology and Environment  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1810-5375","authenticated-orcid":false,"given":"Yan\u2010Qiu","family":"Liang","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry and Environmental Science Guangdong Ocean University  Zhanjiang People's Republic of China"},{"name":"Shenzhen Institute of Guangdong Ocean University  Shenzhen People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,23]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2012-1422"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2012.03.008"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0044-8486(95)01075-0"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2012.03.072"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1365\/s10337-010-1542-9"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2012.07.016"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.aquatox.2008.01.010"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1897\/03-26"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbd.2015.05.001"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2015.11.034"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-1569"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1006\/gcen.1994.1136"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2014.03.001"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/iox085"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.22414"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.13317"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2605.2004.00469.x"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.212401"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.02963"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/1477-7827-6-25"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2010.06.001"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2009.11.006"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2021.05.019"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.76"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408440601123529"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2018.07.001"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/biolre\/iox175"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemosphere.2017.09.127"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemosphere.2018.10.202"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2011.01.014"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpc.2014.09.007"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.molbev.a003833"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1677\/jme.1.01947"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagrm.2011.10.003"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/jai.13828"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2008.01.016"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2004-0418"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-12-0509"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scib.2017.01.007"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2018-00551"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemosphere.2019.125285"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2005.10.014"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemosphere.2009.07.074"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2005.04.006"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0104196"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2014.09.022"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-18-0549"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2020.113446"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0012-1606(03)00436-6"}],"container-title":["Environmental Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/tox.24044","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T08:47:13Z","timestamp":1762591633000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/tox.24044"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,23]]},"references-count":50,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1002\/tox.24044"],"URL":"https:\/\/doi.org\/10.1002\/tox.24044","archive":["Portico"],"relation":{},"ISSN":["1520-4081","1522-7278"],"issn-type":[{"value":"1520-4081","type":"print"},{"value":"1522-7278","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,23]]},"assertion":[{"value":"2022-09-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}