Prevention of retinoic acid-induced early craniofacial abnormalities by vitamin B12 in mice.
OBJECTIVE
The purpose of the present study was to identify the potential effect of prenatal vitamin B12 administration on retinoic acid (RA)-induced early craniofacial abnormalities in mice and to investigate the possible mechanisms by which vitamin B12 reduces malformations.


METHODS
In our study, whole embryo culture was used to explore the effect of vitamin B12 on mouse embryos during the critical period of organogenesis. All embryos were exposed to 0.4 µM RA and different concentrations of vitamin B12 and scored for their growth in the branchial region at the end of a 48-hour culture period. The endothelin-1 (ET-1)/dHAND protein expression levels in the first branchial arch were investigated using an immunohistochemical method.


RESULTS
In the whole embryo culture, 100 and 10 µM vitamin B12 dose-dependently prevented branchial region malformations and decreased craniofacial defects by 90.5% and 77.3%, respectively. ET-1 and dHAND protein levels were significantly increased in vitamin B12-supplemented embryos compared to the RA-exposed group in embryonic branchial region.


CONCLUSIONS
These results suggest that vitamin B12 may prevent RA-induced craniofacial abnormalities via prevention of an RA-induced decrease of ET-1 and dHAND protein levels in the branchial region during the organogenic period. This study may shed new light on preventing craniofacial abnormalities.
Zhang
Zhaofeng
Z
Wang
Junbo
J
Dai
Xiaoqian
X
Ding
Ye
Y
Li
Yong
Y
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis / Q000187:drug effects; D001934:Branchial Region / Q000187:drug effects; D019465:Craniofacial Abnormalities / Q000139:chemically induced / Q000517:prevention & control*; D004305:Dose-Response Relationship, Drug; D046149:Embryo Culture Techniques; D047108:Embryonic Development / Q000187:drug effects; D019332:Endothelin-1 / Q000032:analysis / Q000187:drug effects; D005147:Facial Bones / Q000002:abnormalities / Q000187:drug effects; D005260:Female; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008831:Microcephaly / Q000139:chemically induced / Q000517:prevention & control; D009436:Neural Tube Defects / Q000139:chemically induced / Q000517:prevention & control; D014212:Tretinoin / Q000009:adverse effects*; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000627:therapeutic use*; D014803:Vitamin B Complex / Q000008:administration & dosage / Q000627:therapeutic use*
D051792:Basic Helix-Loop-Helix Proteins; D019332:Endothelin-1; D014212:Tretinoin; D014805:Vitamin B 12; D014803:Vitamin B Complex; C498766:Hand2 protein, mouse