Prevention of retinoic acid-induced early craniofacial abnormalities by folinic acid and expression of endothelin-1/dHAND in the branchial arches in mouse.
Prevention of retinoic acid-induced craniofacial abnormalities by folinic acid, and endothelin-1 (ET-1)/dHAND protein and mRNA expression were investigated in mouse embryos using the whole embryo culture, streptavidin-biotin peroxidase complex method, and whole-mount in situ hybridization. In the whole embryo culture, 1.0 and 0.1 mm-folinic acid dose dependently prevented branchial region malformations and decreased defects by 93 % and 77 %, respectively. Folinic acid at concentrations of 1.0 and 0.1 mm significantly increased ET-1 and dHAND protein expression levels compared to retinoic acid-exposed values in embryonic branchial areas. Folinic acid also increased ET-1 and dHAND mRNA levels in the same region. The present results suggest that folinic acid may prevent retinoic acid-induced craniofacial abnormalities via increasing ET-1 and dHAND levels in the branchial region during the organogenic period.
Zhang
Zhaofeng
Z
Department of Nutrition and Food Hygiene, Laboratory of Molecular Toxicology and Developmental Molecular Biology, School of Public Health, Peking University, Beijing 100083, P.R. China.
Xu
Yajun
Y
Li
Li
L
Han
Jing
J
Zheng
Liping
L
Liu
Peng
P
Li
Yong
Y
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000032:analysis*; D001921:Brain / Q000473:pathology; D001934:Branchial Region / Q000737:chemistry; D019465:Craniofacial Abnormalities / Q000139:chemically induced / Q000517:prevention & control*; D046149:Embryo Culture Techniques / Q000379:methods; D004622:Embryo, Mammalian / Q000473:pathology; D019332:Endothelin-1 / Q000032:analysis*; D005260:Female; D005786:Gene Expression Regulation; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D002955:Leucovorin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D013723:Teratogens; D014212:Tretinoin / Q000009:adverse effects*; D014803:Vitamin B Complex / Q000494:pharmacology*
D051792:Basic Helix-Loop-Helix Proteins; D019332:Endothelin-1; D002955:Leucovorin; D012333:RNA, Messenger; D013723:Teratogens; D014212:Tretinoin; D014803:Vitamin B Complex; C498766:Hand2 protein, mouse