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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD021350-23
Application #
9037036
Study Section
Special Emphasis Panel (ZHD1)
Project Start
Project End
Budget Start
2016-02-01
Budget End
2017-01-31
Support Year
23
Fiscal Year
2016
Total Cost
Indirect Cost
Name
University of Wyoming
Department
Type
DUNS #
069690956
City
Laramie
State
WY
Country
United States
Zip Code
82071
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Spradling-Reeves, Kimberly D; Glenn, Jeremy P; Lange, Kenneth J et al. (2018) The non-human primate kidney transcriptome in fetal development. J Med Primatol 47:157-171
Huber, Hillary F; Li, Cun; Nathanielsz, Peter W (2018) 2D:4D digit ratio is not a biomarker of developmental programming in baboons (Papio hamadryas species). J Med Primatol 47:78-80
Kuo, A H; Li, J; Li, C et al. (2018) Poor perinatal growth impairs baboon aortic windkessel function. J Dev Orig Health Dis 9:137-142
Kuo, Anderson H; Li, Cun; Mattern, Vicki et al. (2018) Sex-dimorphic acceleration of pericardial, subcutaneous, and plasma lipid increase in offspring of poorly nourished baboons. Int J Obes (Lond) 42:1092-1096
Light, Lydia E O; Bartlett, Thad Q; Poyas, Annica et al. (2018) Maternal activity, anxiety, and protectiveness during moderate nutrient restriction in captive baboons (Papio sp.). J Med Primatol :
Kuo, A H; Li, J; Li, C et al. (2017) Prenatal steroid administration leads to adult pericardial and hepatic steatosis in male baboons. Int J Obes (Lond) 41:1299-1302
Proffitt, J Michael; Glenn, Jeremy; Cesnik, Anthony J et al. (2017) Proteomics in non-human primates: utilizing RNA-Seq data to improve protein identification by mass spectrometry in vervet monkeys. BMC Genomics 18:877
Muralimanoharan, Sribalasubashini; Li, Cun; Nakayasu, Ernesto S et al. (2017) Sexual dimorphism in the fetal cardiac response to maternal nutrient restriction. J Mol Cell Cardiol 108:181-193
Li, Cun; Jenkins, Susan; Mattern, Vicki et al. (2017) Effect of moderate, 30 percent global maternal nutrient reduction on fetal and postnatal baboon phenotype. J Med Primatol 46:293-303

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