title: Maternal obesity affects gene expression and cellular development in fetal brains.
abstract: OBJECTIVE
  Female rat neonates reared on a high carbohydrate (HC) milk formula developed chronic hyperinsulinemia and adult-onset obesity (HC phenotype). Furthermore, we have shown that fetal development in the HC intrauterine environment (maternal obesity complicated with hyperinsulinemia, hyperleptinemia, and increased levels of proinflammatory markers) resulted in increased levels of serum insulin and leptin in term HC fetuses and the spontaneous transfer of the HC phenotype to the adult offspring. The objectives of this study are to identify changes in global gene expression pattern and cellular development in term HC fetal brains in response to growth in the adverse intrauterine environment of the obese HC female rat.
  
  
  METHODS
  GeneChip analysis was performed on total RNA obtained from fetal brains for global gene expression studies and immunohistochemical analysis was performed on fetal brain slices for investigation of cellular development in term HC fetal brains.
  
  
  RESULTS
  Gene expression profiling identified changes in several clusters of genes that could contribute to the transfer of the maternal phenotype (chronic hyperinsulinemia and adult-onset obesity) to the HC offspring. Immunohistochemical analysis indicated diminished proliferation and neuronal maturation of stem-like cells lining the third ventricle, hypothalamic region, and the cerebral cortex in HC fetal brains.
  
  
  CONCLUSIONS
  These results suggest that maternal obesity during pregnancy could alter the developmental program of specific fetal brain cell-networks. These defects could underlie pathologies such as metabolic syndrome and possibly some neurological disorders in the offspring at a later age.
authors.affiliation: University at Buffalo, State University of New York, Buffalo, NY, USA.
authors.forename: Ewa K
authors.initials: EK
authors.lastname: Stachowiak
authors.forename: Saji
authors.initials: S
authors.lastname: Oommen
authors.forename: Vihas T
authors.initials: VT
authors.lastname: Vasu
authors.forename: Malathi
authors.initials: M
authors.lastname: Srinivasan
authors.forename: Michal
authors.initials: M
authors.lastname: Stachowiak
authors.forename: Kishorchandra
authors.initials: K
authors.lastname: Gohil
authors.forename: Mulchand S
authors.initials: MS
authors.lastname: Patel
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D004040:Dietary Carbohydrates / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D047109:Fetal Development; D015870:Gene Expression; D020869:Gene Expression Profiling; D006946:Hyperinsulinism / Q000473:pathology; D007031:Hypothalamus / Q000166:cytology / Q000196:embryology* / Q000473:pathology; D007328:Insulin / Q000097:blood; D020738:Leptin / Q000097:blood; D008297:Male; D009765:Obesity / Q000473:pathology*; D010641:Phenotype; D011247:Pregnancy; D051381:Rats
chemical_list: D004040:Dietary Carbohydrates; D007328:Insulin; D020738:Leptin