{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,26]],"date-time":"2025-10-26T21:14:17Z","timestamp":1761513257258},"reference-count":27,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,3,4]],"date-time":"2013-03-04T00:00:00Z","timestamp":1362355200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research Pt B"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>The present study was conducted to evaluate the developmental toxicity in the endometrium and placenta due to <jats:styled-content style=\"fixed-case\">GW<\/jats:styled-content>501516 administration by gavage to pregnant rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p><jats:styled-content style=\"fixed-case\">GW<\/jats:styled-content>501516 was orally administered repeatedly to pregnant rats from gestation day (<jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content>) 6 to 17 at a dose of 0, 30, and 100 mg\/kg\/day. In next study, <jats:styled-content style=\"fixed-case\">GW<\/jats:styled-content>501516 was also orally administered to pregnant rats on <jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content> 7, 8, 9, 10, or 11 at a single dose of 275 or 350 mg\/kg. In these studies, caesarean section was performed to examine the pregnancy outcome on <jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content>21. Additionally, <jats:styled-content style=\"fixed-case\">GW<\/jats:styled-content>501516 was orally administered to pregnant rats on <jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content> 10 at a single dose of 275 mg\/kg. Placentae were subjected for temporal histological examinations on <jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content> 11, 13, 15, or 17.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Placental malformation was induced by repeated administration of <jats:styled-content style=\"fixed-case\">GW<\/jats:styled-content>501516 at a dose of 100 mg\/kg\/day. Single oral administration of <jats:styled-content style=\"fixed-case\">GW<\/jats:styled-content>501516 at a dose of 275 and\/or 350 mg\/kg on <jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content> 8, 9, 10, or 11 induced placental malformation, whereas <jats:styled-content style=\"fixed-case\">GW<\/jats:styled-content>501516 administered on <jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content> 10 was the most effective for increasing placental malformation. Histopathologically, single oral administration of <jats:styled-content style=\"fixed-case\">GW<\/jats:styled-content>501516 on <jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content> 10 induced cystic degeneration associated with cellular lysis of glycogen cells started from <jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content> 15 in the basal zone.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS<\/jats:title><jats:p>High frequency of placental malformation was observed by the administration of <jats:styled-content style=\"fixed-case\">GW<\/jats:styled-content>501516. From <jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content> 8 to 11, especially <jats:styled-content style=\"fixed-case\">GD<\/jats:styled-content> 10, is more sensitive period to induce the placental malformation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/bdrb.21052","type":"journal-article","created":{"date-parts":[[2013,3,5]],"date-time":"2013-03-05T07:56:04Z","timestamp":1362470164000},"page":"164-169","source":"Crossref","is-referenced-by-count":16,"title":["Effect of <scp>PPAR<\/scp>\u03b2\/\u03b4 Agonist on the Placentation and Embryo\u2010Fetal Development in Rats"],"prefix":"10.1002","volume":"98","author":[{"given":"Kyohei","family":"Nishimura","sequence":"first","affiliation":[{"name":"Drug Safely Evaluation Drug Developmental Research Laboratories Toyonaka Osaka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nao","family":"Nakano","sequence":"additional","affiliation":[{"name":"Drug Safely Evaluation Drug Developmental Research Laboratories 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