Partial HIF-1a Deficiency Increases Risk of Diabetic Embryopathy

0379011 - BTÚ 2013 US eng A - Abstrakt
Pavlínková, Gabriela - Bohuslavová, Romana - Sedmera, David - Škvorová, Lada
Partial HIF-1a Deficiency Increases Risk of Diabetic Embryopathy.
Birth Defects Research Part A-Clinical and Molecular Teratology. Roč. 94, č. 5 (2012), s. 319-319. ISSN 1542-0752
Grant CEP: GA ČR GA301/09/0117
Grant ostatní: EU FP7(BE) PIRG02-GA-2007-224760
Výzkumný záměr: CEZ:AV0Z50520701
Klíčová slova: diabetic embryopathy * cardiovascular defects * transcriptional regulation
Kód oboru RIV: FB - Endokrinologie, diabetologie, metabolizmus, výživa

Diabetic pregnancy is associated with a 4- to 10-fold increased incidence of congenital malformations compared with non-diabetic pregnancy. Diabetic embryopathy can affect any developing organ system, although cardiovascular malformations are most common. Although teratogenic effects of maternal diabetes are well documented, the causes remain elusive. Based on our findings that the embryonic expression of Hif1a is dysregulated by maternal diabetes, and the knowledge that Hif1a-/- embryos have major defects in cardiovascular development, we hypothesized that maternal diabetes impairs HIF-1-controlled hypoxia-response pathways and that these pathways are critically involved in the susceptibility to heart defects observed in diabetic embryopathy. We tested this hypothesis in a genetic mouse model of partial HIF-1deficiency by exposing Hif1a+/- embryos to maternal diabetes. We observed a decreased number of embryos per litter and increased incidence of heart malformations, including atrioventricular septal defects and reduced myocardial mass, in diabetes-exposed Hif1a+/- embryos as compared to Wt embryos. We also detected significant differences in expression of mRNAs in diabetes-exposed Hif1a+/- and Wt embryonic hearts, including those encoded by Vegfa, Flt1, and Cited2. Our data strongly suggest that HIF1-regulated pathways could be one of the key molecular pathways involved in the pathogenesis of the teratogenic insult of maternal diabetes.
Trvalý link: http://hdl.handle.net/11104/0210298