Extensive human epidemiological data show that sub-optimal fetal and/or neonatal nutritional environments alter ,rowth and development and predispose individualsto chronic diseases (heart disease, obesity, diabetes and affective disorders) in later life. Compelling, controlled rodent and sheep studies support this view. No systematic non-human primate (NHP) studies are available. Approach: We have built a system to maintain female baboons in a group nvironment while controlling individual nutrient intake. 24 females will be maintained on control (CTR) ad lib diet and 24 on 70% CTR from 30 d gestation (time of implantation) until offspring are removed 9 months postnatally. Offspring will be followed for 2.5 - 3 years. We will establish male and female offspring cohorts. In this Al we include support letters from 27 investigators in the US and abroad who have plans to study these animals in addition to ourselves. The PI understands the importance of clear hypotheses and has received NIH funding continuously since 1976 for hypothesis driven studies. Thus in a Future Work section, classes of hypotheses, addressable with these cohorts are presented. Innovation: Our publications from our newly developed feeding system (several since the 01 submission) are, to our knowledge, the only attempt to determine effects of restricted maternal nutritional intake in a NHP model. Environment: The collaboration between the University of Texas Health Sciences Center, Center for Pregnancy and Newborn Research (CPNR) and the SNPRC provides the expertise necessary to investigate female baboons and their offspring before, during and after pregnancy.The CPNR group has received NHLBI, NICHD,NEI, NINCDS, NIA and NIDDK funding. The PI has extensive collaboration networks in the US and abroad. Overall Significance: The PI serves on a National Children's Study (NCS) workinggroup to follow progeny of 100,000 women for their first 18 yrs. Critical information requiredto evaluate developmentalprogramming cannot be obtained in human pregnancy. Controlled interventional studies of maternal nutritional deprivation with biopsies and repeated blood and body measurements of mothers and offspring are only possible in animals.Baboons mature faster than humans and can provide timely preliminary data to guide the NCS. Advantages of the baboon model we propose: we will use well- characterized non-pregnant females to provide offspring to study extensively from birth to old age in relation to a variety of human conditions that exact a great human health toll. We present plans to share this resource with other investigators in studies relevant to NHLBI, NIDDK, NICHD, NIAID, NEI, NCI, NIA, NINDS, NIMH and NIEHS. The baboon has unique strengths, many not shared by other NHP - a single fetus, a placenta that resembles the human placenta, cross-reactivity of RNA on Affymetrix chips, established instrumented tether systems for chronic instrumented study following recovery from anesthesia. All of these are advantages over other NHP.
