FETAL HEPATIC DEVELOPMENT AND EFFECTS OF MILD MATERNAL NUTRIENT RESTRICTION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 了解精确记录的、改变的母体营养对调节胎儿生长的营养系统的影响，对于了解正常和异常的胎儿发育至关重要。虽然胎儿胰岛素样生长因子（IGF）系统在妊娠期间对不同程度的受控母体营养限制的反应已在啮齿动物和绵羊中进行了广泛研究，但在非人灵长类动物中存在的数据很少。我们确定了MNR对胎儿肝脏IGF系统在一个明确的狒狒模型的影响。 我们研究了妊娠雌性狒狒，这些狒狒在妊娠0.16 - 0.5周（G）期间保持在群体饲养中，并作为自由采食对照（CTR）或全球营养限制为CTR饮食（MNR）的70%进行喂养。在0.5G时，胎儿在异氟醚全身麻醉下通过剖宫产术分娩，测定胎儿和母体血糖以及胎儿血浆生长激素（GH）、皮质醇、硫酸脱氢表雄酮（DHEAS）、IGF-1和IGF结合蛋白（BP）-3。对胎肝右叶进行分析：通过原位杂交（ISH）和定量实时逆转录酶聚合酶链反应（QRT-PCR）分析IGF-I、IGF-II和IGFBP-3 mRNA，通过免疫组织化学（IHC）分析蛋白，通过QRT-PCR分析IGF-1 R、IGF-2 R mRNA，通过IHC分析蛋白，通过ISH分析IGFBP-1 mRNA，通过IHC分析蛋白。 母体营养限制对胎仔体重或肝脏重量无影响，而母体皮质醇升高（p 0.01），胎仔血清：DHEAS升高（p 0.05），IGF-I降低（p=0.06），GH和皮质醇不变。MNR胎仔血清IGFBP-3不变，而血清IGF-I：IGFBP-3比值下降（p <0.05）。尽管MNR胎仔血糖无变化，但肝糖原染色增加，ISH和IHC测量的肝脏IGF-I和II降低，IHC测量的IGF-1 R和-2R降低，ISH和IHC测量的IGFBP-1和-3 mRNA和蛋白增加。

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.