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Logo of bmcgenoBioMed Centralsearchsubmit a manuscriptregisterthis articleBMC Genomics
 
BMC Genomics. 2009; 10: 274.
Published online Jun 18, 2009. doi:  10.1186/1471-2164-10-274
PMCID: PMC2715936
Maternal diabetes alters transcriptional programs in the developing embryo
Gabriela Pavlinkova,1,2,6 J Michael Salbaum,1,3,5 and Claudia Kappencorresponding author1,3,4
1Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE 68198-5455, USA
2Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE 68198-5455, USA
3Munroe-Meyer Institute for Genetics and Rehabilitation, University of Nebraska Medical Center, Omaha, NE 68198-5455, USA
4Department of Maternal Biology, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USA
5Department of Regulation of Gene Expression, Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, LA 70808, USA
6Laboratory of Molecular Pathogenetics, Institute of Biotechnology of the Academy of Sciences of the Czech Republic, Videnska 1083, Prague 4, CZ-14220, Czech Republic
corresponding authorCorresponding author.
Gabriela Pavlinkova: gpavlinkova/at/img.cas.cz; J Michael Salbaum: michael.salbaum/at/pbrc.edu; Claudia Kappen: claudia.kappen/at/pbrc.edu
Received February 10, 2009; Accepted June 18, 2009.
Abstract
Background
Maternal diabetes is a well-known risk factor for birth defects, such as heart defects and neural tube defects. The causative molecular mechanisms in the developing embryo are currently unknown, and the pathogenesis of developmental abnormalities during diabetic pregnancy is not well understood. We hypothesized that the developmental defects are due to alterations in critical developmental pathways, possibly as a result of altered gene expression. We here report results from gene expression profiling of exposed embryos from a mouse diabetes model.
Results
In comparison to normal embryos at mid-gestation, we find significantly altered gene expression levels in diabetes-exposed embryos. Independent validation of altered expression was obtained by quantitative Real Time Polymerase Chain Reaction. Sequence motifs in the promoters of diabetes-affected genes suggest potential binding of transcription factors that are involved in responses to oxidative stress and/or to hypoxia, two conditions known to be associated with diabetic pregnancies. Functional annotation shows that a sixth of the de-regulated genes have known developmental phenotypes in mouse mutants. Over 30% of the genes we have identified encode transcription factors and chromatin modifying proteins or components of signaling pathways that impinge on transcription.
Conclusion
Exposure to maternal diabetes during pregnancy alters transcriptional profiles in the developing embryo. The enrichment, within the set of de-regulated genes, of those encoding transcriptional regulatory molecules provides support for the hypothesis that maternal diabetes affects specific developmental programs.
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