Embryonic defence mechanisms against glucose-dependent oxidative stress require enhanced expression of Alx3 to prevent malformations during diabetic pregnancy.

ABSTRACT: Oxidative stress constitutes a major cause for increased risk of congenital malformations associated to severe hyperglycaemia during pregnancy. Mutations in the gene encoding the transcription factor ALX3 cause congenital craniofacial and neural tube defects. Since oxidative stress and lack of ALX3 favour excessive embryonic apoptosis, we investigated whether ALX3-deficiency further increases the risk of embryonic damage during gestational hyperglycaemia in mice. We found that congenital malformations associated to ALX3-deficiency are enhanced in diabetic pregnancies. Increased expression of genes encoding oxidative stress-scavenging enzymes in embryos from diabetic mothers was blunted in the absence of ALX3, leading to increased oxidative stress. Levels of ALX3 increased in response to gl

SUBMITTER: Garcia-Sanz P 

PROVIDER: S-EPMC5428206 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature