Characterizing the effects of in utero exposure to valproic acid on murine fetal heart development. Issue 19 (29th October 2019)

• Record Type: Journal Article
• Authors: Philbrook, Nicola A.; Nikolovska, Ana; Maciver, Rebecca D.; Belanger, Christine L.; Winn, Louise M.
• Is Part Of: Birth defects research. Volume 111:Issue 19(2019)
• Page Start: 1551
• Page End: 1560
• Publication Date: 2019-10-29
• Subjects: congenital heart defect -- high‐resolution ultrasound -- valproic acid; Teratology -- Periodicals; Abnormalities, Human -- Periodicals; Congenital Abnormalities; Embryo, Mammalian -- abnormalities; Teratology; Abnormalities, Human; Teratology; Periodicals; Periodicals; 616.043
• DOI: 10.1002/bdr2.1610
• Languages: English
• ISSNs: 2472-1727

Abstract

Abstract: Background: Recently, the use of the antiepileptic drug valproic acid (VPA) for the treatment of psychiatric conditions has been on the rise. However, studies have shown that in utero VPA exposure can affect embryonic development, including being associated with congenital heart defects. One proposed mechanism of VPA‐initiated teratogenicity is the inhibition of histone deacetylase, which is involved in the regulation of transcription factors that regulate cardiogenesis. Myocyte enhancing factor 2C ( Mef2c ), a transcription factor involved in the development of cardiac structure and cardiomyocyte differentiation, has been shown to increase in response to in utero VPA exposure, associating with contractile dysfunction and myocardial disorganization. Methods: To characterize the effects of VPA on murine heart development, pregnant CD‐1 mice were dosed with 400 mg/kg of VPA on gestational day (GD) 9. Using high‐resolution ultrasound, we examined the effects of VPA on cardiac contractile function on GD 14–18, with fetal hearts being harvested on GD 19 for histological analysis. Lastly, we conducted quantitative real‐time polymerase chain reaction to measure the relative Mef2c gene expression in GD 16 murine hearts. Results: We observed structural anomalies at GD 19 in the hearts of VPA‐treated mice. Additionally, our results showed alterations in measures of cardiac contractility, with a decrease or increase in cardiac contractile ability in VPA‐treated mice depending on the GD and measurement taken. Conclusions: These results further characterize the effects of VPA on heart development and suggest that alterations in Mef2c gene expression, at least on GD 16, do not mediate VPA‐induced cardiotoxicity in CD‐1 mice.