PLACENTOMAL VASCULAR ADAPTATIONS TO EARLY MATERNAL NUTRIENT RESTRICTION

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 据确定，母羊妊娠早期至中期50%的母体营养限制（NR）改变了胎盘的血管分布，降低了胎盘效率，减少了胎盘向胎儿室输送葡萄糖、氨基酸和脂肪酸，导致胎儿宫内生长受限。 NR母鼠的后代在1月龄时表现出胰岛素抵抗，在8月龄时表现出胰腺衰竭的体征。此外，NR后代表现出血压升高，肾脏肾单位数量减少，9个月大，增加脂肪瘦肉比在他们的尸体。 在2006年，我们开发了一个母体肥胖的绵羊模型，通过从受孕前60天到怀孕期间喂养150%的营养需求。肥胖母羊的体重增加了约50%，妊娠75天，而体重的控制喂养母羊增加了7%。肥胖母羊和胎儿高血糖和高胰岛素血症和母羊表现出升高的胰岛素抵抗相比，对照组在妊娠第75天。来自肥胖母羊的第75天胎仔比对照胎仔重30-40%，并且具有更高的体脂%。尽管与对照组相比，肥胖母羊大多数器官的重量与胎仔重量的增加成比例增加，但胰腺重量显著增加了236%。此外，与对照母羊相比，肥胖母羊胎仔每单位胰腺面积的胰岛素阳性<$-细胞数高50%（P0.05）。肥胖母亲孕育的胎儿胰腺发育过早，加速，可能导致胰岛细胞功能过早丧失，易患糖尿病。

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. It was determined that a 50% maternal nutrient restriction (NR) from early to mid gestation in the ewe altered placentomal vascularity, decreased placental efficiency and reduced the placentomal delivery of glucose, amino acids and fatty acids to the fetal compartment resulting in fetal intra-uterine growth restriction. Offspring from NR dams demonstrated insulin resistance at 1 month of age, and signs of pancreatic failure by 8 months of age. Further, NR offspring exhibited increased blood pressure and decreased kidney nephron numbers by 9 months of age, and an increased fat to lean ratio in their carcasses. In 2006, we developed a sheep model of maternal obesity, by feeding of 150% of nutrient requirements from 60 days before conception through pregnancy. Body weight of obese ewes increased about 50% by day 75 of pregnancy while body weights of control fed ewes gained 7%. Obese ewes and fetuses were hyperglycemic and hyperinsulinemic and ewes exhibited elevated insulin resistance compared to controls on day 75 of pregnancy. Day 75 fetuses from obese ewes were 30-40% heavier than control fetuses and had a higher % body fat. Although the weight of most organs increased in proportion to the increases in fetal weight in obese vs. control ewes, pancreatic weight increased a remarkable 236%. Further, numbers of insulin positive ¿-cells per unit pancreatic area were 50% greater (P0.05) in fetuses from obese vs. control ewes. Untimely, accelerated pancreatic development in fetuses gestated by obese mothers may contribute to premature ¿-cell function loss and predisposition to diabetes.