| First Author | Bohuslavova R | Year | 2013 |
| Journal | J Mol Cell Cardiol | Volume | 60 |
| Pages | 129-41 | PubMed ID | 23619295 |
| Mgi Jnum | J:316441 | Mgi Id | MGI:6837127 |
| Doi | 10.1016/j.yjmcc.2013.04.015 | Citation | Bohuslavova R, et al. (2013) Increased susceptibility of HIF-1alpha heterozygous-null mice to cardiovascular malformations associated with maternal diabetes. J Mol Cell Cardiol 60:129-41 |
| abstractText | Cardiovascular malformations are the most common manifestation of diabetic embryopathy. The molecular mechanisms underlying the teratogenic effect of maternal diabetes have not been fully elucidated. Using genome-wide expression profiling, we previously demonstrated that exposure to maternal diabetes resulted in dysregulation of the hypoxia-inducible factor 1 (HIF-1) pathway in the developing embryo. We thus considered a possible link between HIF-1-regulated pathways and the development of congenital malformations. HIF-1alpha heterozygous-null (Hif1a(+/-)) and wild type (Wt) littermate embryos were exposed to the intrauterine environment of a diabetic mother to analyze the frequency and morphology of congenital defects, and assess gene expression changes in Wt and Hif1a(+/-) embryos. We observed a decreased number of embryos per litter and an 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 the expression of key cardiac transcription factors, including Nkx2.5, Tbx5, and Mef2C, in diabetes-exposed Hif1a(+/-) embryonic hearts compared to Wt littermates. Thus, partial global HIF-1alpha deficiency alters gene expression in the developing heart and increases susceptibility to congenital defects in a mouse model of diabetic pregnancy. |
