@article{HaertleElHajjDittrichetal.2017,
  author    = {Haertle, Larissa and El Hajj, Nady and Dittrich, Marcus and M{\"u}ller, Tobias and Nanda, Indrajit and Lehnen, Harald and Haaf, Thomas},
  title     = {Epigenetic signatures of gestational diabetes mellitus on cord blood methylation},
  series = {Clinical Epigenetics},
  volume    = {9},
  journal   = {Clinical Epigenetics},
  number    = {28},
  doi       = {10.1186/s13148-017-0329-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-159459},
  year      = {2017},
  abstract  = {Background: Intrauterine exposure to gestational diabetes mellitus (GDM) confers a lifelong increased risk for metabolic and other complex disorders to the offspring. GDM-induced epigenetic modifications modulating gene regulation and persisting into later life are generally assumed to mediate these elevated disease susceptibilities. To identify candidate genes for fetal programming, we compared genome-wide methylation patterns of fetal cord bloods (FCBs) from GDM and control pregnancies. Methods and results: Using Illumina's 450K methylation arrays and following correction for multiple testing, 65 CpG sites (52 associated with genes) displayed significant methylation differences between GDM and control samples. Four candidate genes, ATP5A1, MFAP4, PRKCH, and SLC17A4, from our methylation screen and one, HIF3A, from the literature were validated by bisulfite pyrosequencing. The effects remained significant after adjustment for the confounding factors maternal BMI, gestational week, and fetal sex in a multivariate regression model. In general, GDM effects on FCB methylation were more pronounced in women with insulin-dependent GDM who had a more severe metabolic phenotype than women with dietetically treated GDM. Conclusions: Our study supports an association between maternal GDM and the epigenetic status of the exposed offspring. Consistent with a multifactorial disease model, the observed FCB methylation changes are of small effect size but affect multiple genes/loci. The identified genes are primary candidates for transmitting GDM effects to the next generation. They also may provide useful biomarkers for the diagnosis, prognosis, and treatment of adverse prenatal exposures.},
  language  = {en}
}
@article{LehnenZechnerHaaf2013,
  author    = {Lehnen, Harald and Zechner, Urlich and Haaf, Thomas},
  title     = {Epigenetics of gestational diabetes mellitus and offspring health: the time for action is in early stages of life},
  series = {Molecular Human Reproduction},
  volume    = {19},
  journal   = {Molecular Human Reproduction},
  number    = {7},
  doi       = {10.1093/molehr/gat020},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-132165},
  pages     = {415-422},
  year      = {2013},
  abstract  = {The epidemic increase of type 2 diabetes and obesity in developed countries cannot be explained by overnutrition, physical inactivity and/or genetic factors alone. Epidemiologic evidence suggests that an adverse intrauterine environment, in particular a shortage or excess of nutrients is associated with increased risks for many complex diseases later in life. An impressive example for the 'fetal origins of adult disease' is gestational diabetes mellitus which usually presents in 1\% to >10\% of third trimester pregnancies. Intrauterine hyperglycemia is not only associated with increased perinatal morbidity and mortality, but also with increased lifelong risks of the exposed offspring for obesity, metabolic, cardiovascular and malignant diseases. Accumulating evidence suggests that fetal overnutrition (and similarly undernutrition) lead to persistent epigenetic changes in developmentally important genes, influencing neuroendocrine functions, energy homeostasis and metabolism. The concept of fetal programming has important implications for reproductive medicine. Because during early development the epigenome is much more vulnerable to environmental cues than later in life, avoiding adverse environmental factors in the periconceptional and intrauterine period may be much more important for the prevention of adult disease than any (i.e. dietetic) measures in infants and adults. A successful pregnancy should not primarily be defined by the outcome at birth but also by the health status in later life.},
  language  = {en}
}