[Untargeted metabolomics study of dexamethasone-induced congenital cleft palate in New Zealand rabbits].

Abstract

Objective: To investigate the metabolic disorders in placental tissues of dexamethasone induced cleft palate mode. Methods: Twelve pregnant rabbits were randomly divided into dexamethasone group (experimental group, 8) and saline control group (4), and a certain amount of dexamethasone and saline were administered intramuscularly to the experimental and control groups respectively from embryonic days (ED) 13 to 16, and placental tissue samples were collected on day 21 of gestation. The corresponding profiles of the embryonic placental tissue samples were obtained by liquid chromatography-triple tandem quadrupole(LC-MS), and the metabolites of the embryonic placental tissues were characterized by principal component analysis among the dexamethasone-treated group with cleft palate (D-CP group), the dexamethasone-treated group without cleft palate (D-NCP group) and the control group. Results: There were significant metabolic differences among the D-CP group, D-NCP group and control group, with a total of 133 differential metabolites (VIP>1, P<0.05) involving in important metabolic pathways including vitamin B6 metabolism, lysine metabolism, arginine anabolic metabolism, and galactose metabolism. The four metabolites, vitamin B6, galactose, lysine and urea, differed among the three groups (P<0.05). There were significant differences in vitamin B6 (0.960±0.249, 0.856±0.368, 1.319±0.322), galactose (0.888±0.171, 1.033±0.182, 1.127±0.127), lysine (1.551±0.924, 1.789±1.435, 0.541±0.424) and urea (0.743±0.142, 1.137±0.301, 1.171±0.457, respectively) levels among control group, D-NCP group and D-CP group (F=5.90, P=0.008; F=5.59, P=0.009; F=4.26, P=0.025; F=5.29, P=0.012). Conclusions: The results indicated that dexamethasone induced cleft palate may be highly correlated with metabolic disorders including vitamin B6 metabolism, lysine metabolism, arginine anabolic metabolism and galactose metabolism.