[Study of teratogenicity of hyperglycemia on neural tube defects and antagonistic effect of taurine].

Objective: To explore the molecular mechanism of neural tube defects (NTDs) caused by hyperglycemia and thiadiazole and the antagonistic effect of taurine.

Methods: The pregnant mice were divided into hyperglycemia groups, thiadiazole group, taurine groups and control groups. The mRNA and the protein of Pax3 or Cx43 gene were detected respectively by reverse transcription-polymerase chain reaction assay and immunohistochemical method.

Results: As compared with mice treated by thiadiazole-stomach-perfusing, NTDs were significantly increased from mice treated with glucose-injection when blood glucose levels were >or= 13.4 mmol/L. Elevated glucose and thiadiazole could cause changes in Pax3 and Cx43 expression. Hyperglycemia had stronger developmental toxicity on mice embryos. Expression of Pax3 (mRNA 0.97 +/- 0.20, protein 0.11 +/- 0.02) in hyperglycemia group was significantly decreased, while expression of Cx43 (mRNA 7.05 +/- 1.63, protein 0.94 +/- 0.05) was significantly increased, and the relationship of dose-effect was demonstrated. In the thiadiazole group, the expression of Cx43 (mRNA 6.96 +/- 0.73, protein 0.92 +/- 0.12) was significantly stronger than control groups, but there were no significant differences in expression of Pax3 between thiadiazole and its control groups. Both of their teratogenicity could be antagonized by taurine.

Conclusions: This study suggests that congenital malformation associated with diabetic pregnancy is caused by disruption of regulatory genes, Pax3 and Cx43 expression in embryo in response to elevated glucose. Thiadiazole can only disturb the regulation of Cx43 gene causing NTDs. Taurine can correct the disruption caused by the two teratogens.