FETAL HEPATIC DEVELOPMENT AND EFFECTS OF MILD MATERNAL NUTRIENT RESTRICTION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Knowledge of the effects of precisely documented, altered maternal nutrition on trophic systems regulating fetal growth is critical to understanding normal and abnormal fetal development. While responses of the fetal insulin-like growth factor (IGF) system to various degrees of controlled maternal nutrient restriction during pregnancy have been extensively studied in rodents and sheep, few data exist in nonhuman primates. We determined the effects of MNR on the fetal hepatic IGF system in a well-defined baboon model. We have studied pregnant female baboons maintained in group housing and fed as ad libitum controls (CTR) or globally nutrient restricted to 70% of CTR diet (MNR) from 0.16 - 0.5 gestation (G). At 0.5G, fetuses were delivered by cesarean section under isoflurane general anesthesia and fetal and maternal plasma glucose and fetal plasma growth hormone (GH), cortisol, dehydroepiandrosterone sulfate (DHEAS), IGF-I and IGF binding protein (BP)-3 were determined. The right fetal liver lobe was analyzed for: IGF-I, IGF-II and IGFBP-3 mRNA by in situ hybridization (ISH) and quantitative real-time reverse transcriptase polymerase chain reaction (QRT-PCR) and protein by immunohistochemistry (IHC) and IGF-1R, IGF-2R mRNA by QRT-PCR and protein by IHC and IGFBP-1 mRNA by ISH and protein by IHC. Maternal nutrient restriction had no effect on fetal body or liver weight while maternal cortisol increased (p 0.01) and fetal serum: DHEAS rose (p0.05), IGF-I decreased (p=0.06), and GH and cortisol were unchanged. MNR fetal serum IGFBP-3 was unchanged while the serum IGF-I:IGFBP-3 ratio fell (p0.05). Although MNR fetal plasma glucose was unchanged, hepatic glycogen staining increased and hepatic IGF-I and II measured by ISH and IHC decreased, IGF-1R and -2R measured by IHC decreased, and both IGFBP-1 and -3 mRNA and protein, as measured by ISH and IHC, increased.