PLACENTOMAL VASCULAR ADAPTATIONS TO EARLY MATERNAL NUTRIENT RESTRICTION

点击翻译按钮获取中文摘要

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.