The Animal Core (Core B) will oversee all animal requirements of this Program Grant. The baboon model provided by Core B is used equally by all three Projects. The primary objective of Core B is to provide 20 pregnant baboons for C-Section in each year of the 5-year program. In order to achieve this objective, Core B will: (i) provide oversight of animal management and diet administration; (ii) initiate breeding protocols; (iii) maintain records of animal health including diet, morphometric, obstetric and clinical history; (iv) schedule and conduct C-Section surgeries; (v) manage the tissue collection process, sample inventory and the tissue sharing plan including distribution of samples to the Projects and the Genomics, Epigenomics and Proteomics Core (Core C). Core B will consist of a PI (Dr. Nijland), a Co-PI (Dr. Nathanielsz), three animal technicians, a Data Analyst and sub award PI Dr Laura Cox (Texas Biomedical Research Institute; providing fee for service access to the animals and veterinary services). To achieve its objectives, Core B will provide pregnancies exposed to three maternal diets (n=16 per diet): (1) control (CTR), (2) nutrient restricted (MNR, 70% of CTR starting at 30 days (d) of gestation), and (3) intervention (INT, MNR plus CTR leucine content). Fetal tissue samples will be obtained at two gestational ages in the second half of pregnancy, 140d and 180d (n=48 per age; term ~ 185d), chosen to complement the ages studied in the current funding period (90d, 120d and 165d). We know the MNR diet is associated with lUGR, reduced fetal circulating levels of essential amino acids, and structural and functional changes in a range of fetal organs including placenta, brain and kidney relative to CTR. The striking similarities in reproductive physiology and the close evolutionary relationship between baboons and humans, combined with the significant body of information on baboon metabolism available in the literature, the collective experience of our group and members of the SNPRC working with non-human primates, and the lack of relevant data on the mechanisms underlying the impact of MNR on primate fetal development proved a very strong justification for the use of the baboon as the animal model in this proposal.
Reduced fetal nutrient availability results in suboptimal fetal growth and development that increases the risk of lifelong ill health including the predisposition to diabetes and cardiovascular disease. This Program integrates decreased maternal nutrient availability with placental function, fetal nutrient availability and fetal brain and kidney development. We set out to study and identify key mechanisms in maternal x fetal nutrient environment interaction that will provide insight when designing treatment strategies.
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