Effects of excess vitamin A on development of cranial neural crest-derived structures: A neonatal and embryologic study
Article first published online: 13 SEP 2000
Copyright © 2000 Wiley-Liss, Inc.
Volume 62, Issue 4, pages 214–226, October 2000
How to Cite
Mulder, G. B., Manley, N., Grant, J., Schmidt, K., Zeng, W., Eckhoff, C. and Maggio-Price, L. (2000), Effects of excess vitamin A on development of cranial neural crest-derived structures: A neonatal and embryologic study. Teratology, 62: 214–226. doi: 10.1002/1096-9926(200010)62:4<214::AID-TERA7>3.0.CO;2-N
- Issue published online: 13 SEP 2000
- Article first published online: 13 SEP 2000
- Manuscript Accepted: 7 APR 2000
- Manuscript Received: 3 MAR 1999
- National Institute of Diabetes and Digestive and Kidney Disease. Grant Number: 5 P30 DK35816
- National Center for Research Resources. Grant Number: 2T32RR07019
- National Institute of Child Health and Human Development. Grant Number: T32 HD07456
Vitamin A and its metabolites have been shown to be teratogenic in animals and humans producing defects of neural crest derived structures that include abnormalities of the craniofacial skeleton, heart, and thymus. Our prior studies with retinoic acid have established that gestational day (gd) 9 is a sensitive embryonic age in the mouse for inducing craniofacial and thymic defects.
We exposed pregnant mice to variable doses of vitamin A (retinyl acetate) on gd 9 and embryos were evaluated for changes in developing pharyngeal arch and pouch morphology, neural crest cell migration and marker gene expression. Additionally, we investigated whether a single organ system was more sensitive to low doses of vitamin A and could potentially be used as an indicator of vitamin A exposure during early gestation.
High (100 mg/kg) and moderate (50 and 25 mg/kg) doses of vitamin A resulted in significant craniofacial, cardiac outflow tract and thymic abnormalities. Low doses of vitamin A (10 mg/kg) produced craniofacial and thymic abnormalities that were mild and of low penetrance. Exposed embryos showed morphologic changes in the 2nd and 3rd pharyngeal arches and pouches, changes in neural crest migration, abnormalities in cranial ganglia, and altered expression of Hoxa3.
These animal studies, along with recent epidemiologic reports on human teratogenicity with vitamin A, raise concerns about the potential for induction of defects (perhaps subtle) in offspring of women ingesting even moderate to low amounts of supplemental vitamin A during the early gestational period. Teratology 62:214–226, 2000. © 2000 Wiley-Liss, Inc.