{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:13:15Z","timestamp":1790838795979,"version":"4.1.0"},"reference-count":61,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2014,10,12]],"date-time":"2014-10-12T00:00:00Z","timestamp":1413072000000},"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"],"published-print":{"date-parts":[[2014,12]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Selective serotonin reuptake inhibitor (SSRI) use in pregnancy has been linked to craniofacial birth defects. Little is known about the effects of serotonin or SSRIs on craniofacial development. Here, we provide evidence that citalopram (SSRI) alters the osteogenic profile of murine calvarial cells and leads to craniofacial dysmorphology.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We used mouse calvarial pre\u2010osteoblast cells (MC3T3\u2010E1) to study the biochemical profile (microarray and quantitative reverse transcription polymerase chain reactions) after treatment with a titrated dose of citalopram. We used C57BL\u20106 wild\u2010type breeders to produce litters treated with a clinical dose of citalopram during the third trimester of pregnancy. We used micro\u2010computed tomography and morphometric measures to determine effects on craniofacial development.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Controls included untreated cells and age matched untreated litters. We observed decreases in proliferation and increases in alkaline phosphatase activity after citalopram exposure. We confirmed altered expression of genes linked to osteogenesis including <jats:italic>Ocn<\/jats:italic> and significant increase in expression of <jats:italic>Alp<\/jats:italic> after 7 days of treatment. Our data suggest altered expression of several genes related to craniofacial development (<jats:italic>Fgf2<\/jats:italic>, <jats:italic>Fgfr2<\/jats:italic>, <jats:italic>Tgf\u03b2r2 Irs1<\/jats:italic>, <jats:italic>Igf1<\/jats:italic>) and statistically significant changes in expression for (<jats:italic>Col2a1<\/jats:italic>, <jats:italic>Gdf6<\/jats:italic>, <jats:italic>Hmox1<\/jats:italic>, and <jats:italic>Notch1<\/jats:italic>). We also observed changes in regulation of the serotonin pathway (<jats:italic>Sert<\/jats:italic>, <jats:italic>Tph1<\/jats:italic>, <jats:italic>Tph2<\/jats:italic>, <jats:italic>Htr2a<\/jats:italic>, <jats:italic>Lrp5<\/jats:italic>) after treatment with citalopram. After in utero exposure to citalopram, mice displayed shorter narrow snouts, more globular skulls and several craniofacial anomalies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our results provide confirmatory evidence that citalopram exposure is associated with cellular and morphological alterations of the craniofacial complex, which may have important implications for use during pregnancy. Birth Defects Research (Part A), 2014. \u00a9 2014 Wiley Periodicals, Inc. 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