Effects of Retinoic Acid on the Expressions of Vangl1 and Vangl2 in Mouse Fetuses

This study reports the effects of retinoic acid on the spatiotemporal expressions of Vangl1 and Vangl2 in mouse fetuses. A single dose of 120 mg/kg body weight of all-trans-retinoic acid suspended in olive oil was administered intragastrically to each pregnant BALB/C mice on embryonic day (E) 9.5 (group 1, G1) or E10.5 (group 2, G2); mice treated with pure olive oil on E9.5 or E10.5 served as control groups. The expression of Vangl1 and Vangl2 in fetuses was investigated by reverse transcriptase PCR (RT-PCR) and their spatial and temporal expression was detected by whole-mount in situ hybridization (WISH) on E10.5, E11.5, E13.5, E15.5, E17.5, and E19.5, respectively. The study indicated that the incidence of neural tube defects (NTDs) in live birth and craniofacial NTD rate were significantly higher in G1 (100% and 25.6%) than that in G2 (78.2% and 5.7%), both P<0.01. Vangl1 and Vangl2 were strongly expressed throughout neurulation in embryos of control groups. G1 embryos exhibited a dramatic downregulation of Vangl1 and Vangl2 expression from cranial regions to posterior neuropore compared with the control group of G1 (all P<0.01). In contrast, both transcripts in G2 embryos were significantly downregulated and weakly expressed in whole embryos on E11.5 and in the spinal region of the neural tube from E15.5 to E19.5, but moderately downregulated in the cranial region of the neural tube from E15.5 to E19.5 (all P<0.01). In conclusion, Vangl1 and Vangl2 transcript downregulation might be implicated in the occurrence of mouse NTDs induced by retinoic acid.