Molecular Changes Induced by the Teratogenic Environment of Maternal Diabetes in Embryonic Hearts

0372378 - BTÚ 2012 US eng C - Conference Paper (international conference)
Pavlínková, Gabriela - Bohuslavová, Romana - Kuthanová, Lada - Sedmera, David - Bloudičková, Sylvie
Molecular Changes Induced by the Teratogenic Environment of Maternal Diabetes in Embryonic Hearts.
BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY. MALDEN: WILEY-BLACKWELL, 2011, s. 339-339. ISSN 1542-9768.
[51th Annual Meeting of the Teratology Society. San Diego, California (US), 25.06.2011-29.06.2011]
Institutional research plan: CEZ:AV0Z50520701
Keywords : Diabetic embryopathy * cardiovascular defects * expression profiling
Subject RIV: EB - Genetics ; Molecular Biology

Although teratogenic effects of maternal diabetes are well documented, the causes remain elusive. We hypothesize that HIF1a-controlled hypoxia-response pathways are critically involved in the susceptibility to congenital defects observed in diabetic embryopathy. We have analyzed the frequencies and morphology of congenital defects and changes in the expression of HIF1 target genes in Hif1a+/- and wildtype (wt) embryos exposed to maternal diabetes. The Hif1a+/- embryos from diabetic pregnancy showed an increased rate of cardiovascular defects of 62.5% as compared to 36.8% of wt diabetes-exposed embryos with a range of cardiac malformations. We also detected significant changes in the gene expression in diabetes-exposed Hif1a+/- embryos as compared to diabetes-exposed wt. Limiting levels of Hif1α has compromised embryonic development under the conditions of maternal diabetes. Our data strongly suggest that HIF1-activated pathways could be one of the key molecular pathways in the pathogenesis of diabetes-induced congenital defects.
Permanent Link: http://hdl.handle.net/11104/0205710