Related Experiment Video
Updated: Apr 22, 2026
Analysis of Craniomaxillofacial Malformations in Mice Using Three-dimensional Microcomputed Tomography
Published on: January 17, 2025
Selective serotonin reuptake inhibitor exposure alters osteoblast gene expression and craniofacial development in
James J Cray1, Seth M Weinberg, Trish E Parsons
1Departments of Oral Health Sciences, Medical University of South Carolina, Charleston, South Carolina.
Background:
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.
Methods:
We used mouse calvarial pre-osteoblast cells (MC3T3-E1) to study the biochemical profile (microarray and quantitative reverse transcription polymerase chain reactions) after treatment with a titrated dose of citalopram. We used C57BL-6 wild-type breeders to produce litters treated with a clinical dose of citalopram during the third trimester of pregnancy. We used micro-computed tomography and morphometric measures to determine effects on craniofacial development.
Results:
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 Ocn and significant increase in expression of Alp after 7 days of treatment. Our data suggest altered expression of several genes related to craniofacial development (Fgf2, Fgfr2, Tgfβr2 Irs1, Igf1) and statistically significant changes in expression for (Col2a1, Gdf6, Hmox1, and Notch1). We also observed changes in regulation of the serotonin pathway (Sert, Tph1, Tph2, Htr2a, Lrp5) after treatment with citalopram. After in utero exposure to citalopram, mice displayed shorter narrow snouts, more globular skulls and several craniofacial anomalies.
Conclusion:
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.
Insights
Selective serotonin reuptake inhibitor (SSRI) use during pregnancy, like with citalopram, may cause craniofacial birth defects. This study shows citalopram alters bone cell development and leads to craniofacial abnormalities in mice.
Area of Science:
- Developmental biology
- Pharmacology
- Genetics
Background:
- Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed during pregnancy.
- SSRIs have been anecdotally linked to craniofacial birth defects.
- The specific effects of SSRIs on craniofacial development remain largely unknown.
Purpose of the Study:
- To investigate the impact of citalopram, an SSRI, on the osteogenic profile of murine calvarial cells.
- To determine the effects of in utero citalopram exposure on craniofacial development in mice.
Main Methods:
- Murine calvarial pre-osteoblast cells (MC3T3-E1) were treated with citalopram to analyze gene expression related to osteogenesis.
- C57BL-6 mice were exposed to a clinical dose of citalopram during the third trimester of pregnancy.
- Micro-computed tomography and morphometric analyses were performed on offspring to assess craniofacial morphology.
Main Results:
- Citalopram exposure decreased cell proliferation and increased alkaline phosphatase activity in vitro.
- Altered expression of key osteogenesis genes (e.g., Alp, Ocn) and craniofacial development genes (e.g., Fgf2, Notch1) was observed.
- In utero exposure resulted in craniofacial anomalies, including shorter snouts and more globular skulls in mice.
Conclusions:
- Citalopram exposure induces cellular and morphological changes in the craniofacial complex.
- These findings suggest potential risks associated with citalopram use during pregnancy.
- Further research is warranted to understand the implications for human fetal development.
