title: The frontal cortex IGF system is down regulated in the term, intrauterine growth restricted fetal baboon.
abstract: OBJECTIVE
  The IGF system exerts systemic and local actions during development. We previously demonstrated that fetal cerebral cortical IGF1 is reduced at 0.5 gestation in our IUGR baboon nonhuman primate model. We hypothesized that by term protein expression of several key IGF system stimulatory peptide pathway components and downstream nutrient signaling effectors of IGF, mammalian target of rapamycin (mTOR) and S6, would decrease, indicating reduced cellular nutrient uptake and protein synthesis.
  
  
  METHODS
  We fed 7 control baboons ad libitum while 6 baboons ate a globally reduced diet (70% of feed eaten by controls) from 0.16 gestation through pregnancy that produces IUGR. Fetuses were removed at Cesarean section at 0.9 gestation. Frontal cortex sections were stained for IGFI, IGFII, IGFRI, IGFR2, IGFBP2, 3, 5 and 6, and mTOR and ribosomal protein S6 and double stained with NeuN a neuron-specific nuclear antigen.
  
  
  RESULTS
  All proteins stained neuronal cytoplasm except IGFRI which showed only glial cell cytoplasmic and blood vessel staining. IUGR fetuses showed decreased frontal cortical immunoreactive IGFI, IGFII, IGFRI, IGFBP2, 5 and 6, and mTOR and S6 (p < 0.05). IGFBP3 increased (p < 0.05) and IGFR2 was unchanged (p > 0.05). There were no differences between male and female fetal brains.
  
  
  CONCLUSIONS
  When fetal nutrient availability is decreased, IUGR down regulates the IGF system and its mTOR signaling pathway in the fetal frontal cortex coincident with slowed growth. These findings emphasize the importance of the local tissue IGF system in fetal primate brain development.
authors.affiliation: The University of Texas Health Science Center San Antonio, Center for Pregnancy and Newborn Research, Dept. OB/GYN, San Antonio, TX 78229, USA.
authors.forename: L
authors.initials: L
authors.lastname: Xie
authors.forename: I
authors.initials: I
authors.lastname: Antonow-Schlorke
authors.forename: M
authors.initials: M
authors.lastname: Schwab
authors.forename: T J
authors.initials: TJ
authors.lastname: McDonald
authors.forename: P W
authors.initials: PW
authors.lastname: Nathanielsz
authors.forename: C
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D015536:Down-Regulation; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism* / Q000473:pathology; D005333:Fetus / Q000378:metabolism; D005625:Frontal Lobe / Q000196:embryology / Q000378:metabolism*; D005865:Gestational Age; D018969:Insulin-Like Growth Factor Binding Proteins / Q000378:metabolism*; D008297:Male; D010215:Papio; D011247:Pregnancy; D015398:Signal Transduction; D013002:Somatomedins / Q000378:metabolism*; D047929:Term Birth / Q000378:metabolism*
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins
keywords: Baboon fetus; Binding proteins; Brain; IGF; IGF receptors; IGFI; IUGR; S6; mTOR
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