{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T22:48:35Z","timestamp":1782514115071,"version":"3.54.5"},"reference-count":60,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T00:00:00Z","timestamp":1660176000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science KAKENHI","doi-asserted-by":"crossref","award":["21K6822"],"award-info":[{"award-number":["21K6822"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science KAKENHI","doi-asserted-by":"crossref","award":["21K19538"],"award-info":[{"award-number":["21K19538"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Many industrial chemicals have been reported as antiandrogenic substances. Exposure to these substances represents a potential risk to human health, particularly to the development of reproductive organs such as embryonic external genitalia (eExG). Currently, there is a need for more assay systems that can elucidate the toxicological actions and mechanisms of endocrine-disrupting chemicals. In this study, we show that the eExG slice culture assay is useful for the evaluation of the differing modes of action of endocrine-disrupting chemicals on urethra formation. We assessed the possible endocrine-disrupting activity of 3 chemicals with reported antiandrogenic function, diazinon, dibutyl phthalate, and fenitrothion (FNT) on eExG slices. Exposure to FNT, but not diazinon and dibutyl phthalate, induced defects of androgen-induced urethral masculinization and reduced expression of the androgen-target gene Mafb. Live imaging analyses showed that FNT treatment inhibited androgen-dependent MAFB induction within 12\u2009h. Furthermore, FNT-treated tissue slices showed reduced expression of the androgen receptor. These results indicate that FNT disrupts androgen signaling by reduction of androgen receptor expression during androgen-induced eExG masculinization. This study thus highlights the importance of animal models, which allow for the effective assessment of tissue-specific endocrine-disrupting activity to further reveal the etiology of chemical-induced congenital anomalies.<\/jats:p>","DOI":"10.1093\/toxsci\/kfac085","type":"journal-article","created":{"date-parts":[[2022,8,11]],"date-time":"2022-08-11T18:27:22Z","timestamp":1660242442000},"page":"13-22","source":"Crossref","is-referenced-by-count":4,"title":["Exposure to the Organophosphate Pesticide Fenitrothion Directly Induced Defects in Mouse Embryonic External Genitalia"],"prefix":"10.1093","volume":"190","author":[{"given":"Alvin R","family":"Acebedo","sequence":"first","affiliation":[{"name":"Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University , Wakayama 641-8509, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mellissa C","family":"Alcantara","sequence":"additional","affiliation":[{"name":"Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University , Wakayama 641-8509, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuyoshi","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Laboratory of Hygienic Chemistry and Molecular Toxicology, Gifu Pharmaceutical University , Gifu 501-1196, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takehiko","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Department of Regenerative Medicine, Graduate School of Medicine, Yokohama City University , Yokohama, Kanagawa 236-0004, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gen","family":"Yamada","sequence":"additional","affiliation":[{"name":"Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University , Wakayama 641-8509, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6872-5292","authenticated-orcid":false,"given":"Kentaro","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University , Wakayama 641-8509, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,8,11]]},"reference":[{"key":"2022102808011016300_kfac085-B1","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1292\/jvms.19-0452","article-title":"Effects of several organophosphates on hepatic cytochrome p450 activities in rats","volume":"82","author":"Abdou","year":"2020","journal-title":"J. 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