Fol. Biol. 2014, 60, 244-251
Does Folic Acid Supplementation Rescue Defects in ECE-1-Deficient Mouse Embryos?
Endothelin (ET) signalling is essential for normal embryonic development. Disruption of this pathway leads to defects in the development of subsets of cranial and cephalic neural crest derivatives. Endothelin-converting enzyme 1 (ECE-1) is a ratelimiting step in the biosynthesis of ET-1. Recently, there has been considerable interest in the protective role of folic acid (FA) against congenital anomalies via increasing the expression of ET-1. We have tested whether FA supplementation can rescue craniofacial and cardiac defects observed in the ECE1–/– embryos. ECE1+/– mice were caged together to obtain litters containing embryos of all possible genotypes. The treatment group had the diet supplemented with 20 mg/kg of FA from the day of discovery of the vaginal plug. FA supplementation did not result in modified proportions of the genotypes, indicating no rescue of the embryonic mortality. There was also no effect on the litter size. Craniofacial and cardiac defects were likewise identical in the ECE1–/– embryos of both groups. There was a mild but significant reduction in the embryo size in wild-type and heterozygous FA-supplemented embryos, and there were haemorrhages in the wild-type supplemented embryos at ED14.5. Expression of ET receptor A detected by immunohistochemistry was up-regulated in the ECE1–/– embryos, but FA supplementation had no effects on the distribution of staining intensity. We conclude that FA is not able to rescue the phenotype in this model, suggesting an alternative pathway for its action. These results also caution against indiscriminate use of dietary supplements in attempts to prevent congenital anomalies.
Keywords
endothelin-converting enzyme, mice, endothelin 1, cardiac malformations, endothelin receptor.
Funding
The project was supported by the Grant Agency of the Czech Republic P302/11/1308, 13-12412S, Ministry of Education, Youth and Sports of the Czech Republic, PRVOUK P35/LF1/5, and Academy of Sciences RVO: 67985823. Barbora Šaňková was also supported by a SVV training grant from Charles University in Prague.
References
Copyright
This is an open-access article distributed under the terms of the Creative Commons Attribution License.
