title: Acquired alterations of hypothalamic gene expression of insulin and leptin receptors and glucose transporters in prenatally high-glucose exposed three-week old chickens do not coincide with aberrant promoter DNA methylation.
abstract: BACKGROUND
  Prenatal exposures may have a distinct impact for long-term health, one example being exposure to maternal 'diabesity' during pregnancy increasing offspring 'diabesity' risk. Malprogramming of the central nervous regulation of body weight, food intake and metabolism has been identified as a critical mechanism. While concrete disrupting factors still remain unclear, growing focus on acquired epigenomic alterations have been proposed. Due to the independent development from the mother, the chicken embryo provides a valuable model to distinctively establish causal factors and mechanisms.
  
  
  OBJECTIVE
  The aim of this study was to determine the effects of prenatal hyperglycemia on postnatal hypothalamic gene expression and promoter DNA methylation in the chicken.
  
  
  RESULTS
  To temporarily induce high-glucose exposure in chicken embryos, 0.5 ml glucose solution (30 mmol/l) were administered daily via catheter into a vessel of the chorioallantoic egg membrane from days 14 to 17 of incubation. At three weeks of postnatal age, body weight, total body fat, blood glucose, mRNA expression (INSR, LEPR, GLUT1, GLUT3) as well as corresponding promoter DNA methylation were determined in mediobasal hypothalamic brain slices (Nucleus infundibuli hypothalami). Although no significant changes in morphometric and metabolic parameters were detected, strongly decreased mRNA expression occurred in all candidate genes. Surprisingly, however, no relevant alterations were observed in respective promoter methylation.
  
  
  CONCLUSIONS
  Prenatal hyperglycemia induces strong changes in later hypothalamic expression of INSR, LEPR, GLUT1, and GLUT3 mRNA. While the chicken provides an interesting approach for developmental malprogramming, the classical expression regulation via promoter methylation was not observed here. This may be due to alternative/interacting brain mechanisms or the thus far under-explored bird epigenome.
authors: Clinic of Obstetrics, Division of 'Experimental Obstetrics', Charité-University Medicine Berlin, Campus Virchow-Klinikum, Berlin, Germany.
authors: Rebecca C
authors: RC
authors: Rancourt
authors: Clinic of Obstetrics, Division of 'Experimental Obstetrics', Charité-University Medicine Berlin, Campus Virchow-Klinikum, Berlin, Germany.
authors: Karen
authors: K
authors: Schellong
authors: Clinic of Obstetrics, Division of 'Experimental Obstetrics', Charité-University Medicine Berlin, Campus Virchow-Klinikum, Berlin, Germany.
authors: Raffael
authors: R
authors: Ott
authors: Humboldt-University of Berlin, Institute of Biology, Berlin, Germany.
authors: Semen
authors: S
authors: Bogatyrev
authors: Humboldt-University of Berlin, Institute of Biology, Berlin, Germany.
authors: Barbara
authors: B
authors: Tzschentke
authors: Clinic of Obstetrics, Division of 'Experimental Obstetrics', Charité-University Medicine Berlin, Campus Virchow-Klinikum, Berlin, Germany.
authors: Andreas
authors: A
authors: Plagemann
mesh_terms: D000818:Animals; D001786:Blood Glucose; D001835:Body Weight; D002642:Chick Embryo; D002645:Chickens; D019175:DNA Methylation; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism*; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics*; D007031:Hypothalamus / Q000378:metabolism*; D008297:Male; D011401:Promoter Regions, Genetic; D011972:Receptor, Insulin / Q000235:genetics*; D054411:Receptors, Leptin / Q000235:genetics*; D012737:Sex Factors
chemical_list: D001786:Blood Glucose; D051246:Glucose Transport Proteins, Facilitative; D054411:Receptors, Leptin; D011972:Receptor, Insulin; D005947:Glucose