Vitamin A improves Pax3 expression that is decreased in the heart of rats with experimental diaphragmatic hernia

Background/Aims

Rats with nitrofen-induced congenital diaphragmatic hernia (CDH) have hypoplasia and malformations of the heart. The mechanism of action of nitrofen involves changes in neural crest signaling. Pax3 function is required for cardiac neural crest cells to complete their migration to the developing heart. Vitamin A improves heart hypoplasia. The aims of this study were to examine whether Pax3 expression is decreased in the heart of E13 E15 and E21 rats exposed to nitrofen and if vitamin A reverts this effect.

Material and Methods

Pregnant rats received either 100 mg nitrofen or olive oil on E9.5. Each group was divided into 2 subgroups according to the subsequent treatment with intragastric vitamin A (15000 IU) or vehicle on E10.5 to E11.5. The pups were recovered on E13, E15 and E21 and the hearts were dissected out. Pax3 mRNA expression was determined by quantitative real time PCR. Comparisons among groups were made with ANOVA and Bonferroni post hoc tests with a threshold of significance of P < .05.

Results

Pax3 mRNA expression was significantly decreased on E13 and E15 in the hearts of nitrofen-treated embryos and it remained decreased although not significantly on E21. Vitamin A recovered this expression on E13, partially on E15 and above normal levels on E21.

Conclusions

Pax3 is underexpressed in the hearts of nitrofen exposed embryonal rats on days 13th and 15th of gestation and tends to be lower than normal near term. Vitamin A up-regulates this expression on the 3 end points. The mechanism of action of Pax3 should be further investigated because it could be one of the targets for future prenatal transplacental intervention.