Suppression of retinoic acid receptors may contribute to embryonic skeleton hypoplasia in maternal rats with chronic vitamin A deficiency.
Vitamin A (VA) is essential for embryonic development and the retinoic acid receptors (RARs) are crucial in mediating the diverse actions of VA in embryogenesis. However, the association between RARs and teratogenicity on skeleton growth and development of vitamin A deficiency (VAD) is not clear. In this present study, weaning female Sprague-Dawley rats were fed purified diets containing graded levels of VA (0, 0.4, 4 IU/g diet) for 70 days before mating, and some of them were supplemented with VA (10 IU/g diet) through pregnancy. Embryos were recovered at embryonic day 19.5 (E19.5) for the analysis of skeleton growth and development and the E12.5 embryos were collected for analysis of select mRNA of RARalpha, RARbeta, RARgamma, Hoxa2, Hoxa5 and Hoxa9. Normal gene expressions and morphogenesis were observed in all embryos from group fed 4 IU/g diet. The embryos from group fed VA-free diet showed a comprehensive suppression of all the genes and general fetal resorption. The embryos from group fed 0.4 IU/g diet exhibited a moderate down-regulation on RARbeta, RARgamma, Hoxa2 and Hoxa5, and the E19.5 fetuses displayed a series of skeletal hypoplasia. The VA supplement groups fed 10 IU/g diet displayed normal gene expressions and morphologic appearances. These findings suggested that the suppression of RARs resulted from VAD could disturb the proper expression of homeobox genes, which might, at least in part, contribute to the embryonic skeletal hypoplasia due to maternal rats with chronic VAD.
Li
Na
N
Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
Sun
Shanshan
S
Wang
Di
D
Yao
Ping
P
Yang
Xuefeng
X
Yan
Hong
H
Du
Yukai
Y
Ying
Chengjiang
C
Liu
Liegang
L
D000818:Animals; D001483:Base Sequence; D001842:Bone and Bones / Q000196:embryology* / Q000473:pathology; D017931:DNA Primers; D005260:Female; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018168:Receptors, Retinoic Acid / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014802:Vitamin A Deficiency / Q000473:pathology*
D017931:DNA Primers; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid