{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:29:25Z","timestamp":1790166565635,"version":"4.1.0"},"reference-count":68,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2016,7,7]],"date-time":"2016-07-07T00:00:00Z","timestamp":1467849600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100012779","name":"the R\u00e9seau Qu\u00e9b\u00e9cois de Recherche sur les M\u00e9dicaments","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012779","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Research Chair on Medications and Pregnancy"},{"name":"Fonds de Recherche du Qu\u00e9bec"},{"name":"Sant\u00e9, McGill University"},{"name":"March of Dimes Social and Behavioral Sciences Research","award":["12-FY12-179"],"award-info":[{"award-number":["12-FY12-179"]}]},{"name":"the R\u00e9seau Qu\u00e9b\u00e9cois de la Reproduction (RQR)-FRQ-Nature et Technologie"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Birth Defects Research"],"published-print":{"date-parts":[[2016,12]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Human studies are inconsistent with respect to an association between treatment with selective serotonin and serotonin\u2013norepinephrine reuptake inhibitors (SSRI\/SNRIs) and an increase in the incidence of congenital heart defects. Here we tested the hypothesis that <jats:italic>in utero<\/jats:italic> exposure to venlafaxine, a highly prescribed SNRI, increases the incidence of fetal heart defects and alters placental and fetal heart serotonin signaling in the rat.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Timed\u2010pregnant Sprague Dawley rats were gavaged daily with venlafaxine hydrochloride (0, 3, 10, 30, or 100 mg\/kg\/day) from gestation day 8 to 20. On gestation day 21, fetuses were examined for external and internal malformations; placentas and fetal hearts were collected for the analysis of gene expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Venlafaxine had no effect on the number of live fetuses, fetal body weights, or external morphology in the absence of maternal toxicity. However, venlafaxine significantly increased the placental index (fetal body\/placental weight ratio) and the incidence of fetal cardiac anomalies. Venlafaxine exposure decreased placental expression of the serotonin transporter (SERT\/<jats:italic>Slc6a4<\/jats:italic>) at the transcript and protein levels. In contrast, venlafaxine increased SERT expression in the hearts of female, but not male, fetuses. Expression of the serotonin 2B receptor (5\u2010HT<jats:sub>2B<\/jats:sub>\/<jats:italic>Htr2b<\/jats:italic>) and of fibroblast growth factor 8 was induced in fetal hearts.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>In utero<\/jats:italic> venlafaxine exposure altered the placental index and induced fetal cardiac anomalies in rats. We propose that the increased incidence of cardiac anomalies is mediated through alterations in serotonin signaling in the placenta and fetal heart. Birth Defects Research (Part A), 2016. \u00a9 2016 Wiley Periodicals, Inc. 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