Significance: The overall PO1 goal PO1 is to study effects of global maternal (M) nutrient restriction (NR), (MNR - mothers eat 70% feed eaten by ad lib controls (CTR). Sub-optimal fetal (F) organ growth and development are major problems associated with increased neonatal death and long term morbidity. Underlying mechanisms are poorly understood. Whilst primary causes are diverse, poor F development is generally secondary to F NR. Rodent and sheep studies provide insight but parallel nonhuman primate (NHP) data are minimal. Hypothesis: exposure of baboons to MNR adversely impacts growth and key cellular processes in placenta, F brain and F kidney. We hypothesize: 30% global MNR: 1: impairs growth;2: impairs angiogenesis;3: impacts the IGF system;4: alters cellular nutrient sensing;5. influences programmed cell death, in an F sex and developmental stage specific manner. Approach: We use a 30% global MNR baboon model housed in groups to compare MNR with TR mechanisms. Projects evaluate I) placenta, II) F brain and III) F kidney effects of MNR at 0.33, 0.5. 0.66 and 0.9 gestation (G) to determine cumulative outcomes. We combine 1) stereological;2) biochemical - cell signaling and gene function, with global (gene arrays, proteomics) and candidate gene/protein (PCR, in situ hybridization, Western blot and immunohistochemistry) and in vitro (matrigel) and 3) in vivo approaches. Innovation: Our preliminary data show that 30% MNR produces F NR (decreased F blood urea nitrogen, amino acids and growth factors). No other group uses NHP to evaluate MNR effects on placental and F organ structural and functional development in studies not possible in human fetuses. Synergy: All projects study similar mechanisms and use the same baboons to investigate overlapping pathways and provide information on organ similarities and differences. Environment: University of Texas Health Sciences Center and Southwest Foundation for Biomedical Research have collaborated for many years. We have experienced and interactive Cores. Extensive preliminary data support the hypotheses. Investigators: In addition to new investigators, PO1 investigators have collaborated for a total of over 85 years. Summary: We apply for Years 16-20 support. Lay description: We pass more milestones during in utero development than any other time of life. Sub-optimal conditions in utero alter placental function and brain and kidney development. Our studies will help determine mechanisms by which conditions experienced in the womb predispose to high blood pressure, obesity and diabetes in later life. Clinicians will use the information to understand optimal life style and diet in pregnancy.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD021350-20
Application #
8129576
Study Section
Special Emphasis Panel (ZHD1-MCHG-B (PN))
Program Officer
Ilekis, John V
Project Start
1997-04-01
Project End
2013-07-31
Budget Start
2011-08-01
Budget End
2013-07-31
Support Year
20
Fiscal Year
2011
Total Cost
$1,250,855
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Obstetrics & Gynecology
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
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
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
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
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
Schlabritz-Loutsevitch, N; Apostolakis-Kyrus, K; Krutilina, R et al. (2016) Pregnancy-driven cardiovascular maternal miR-29 plasticity in obesity. J Med Primatol 45:297-303
Pantham, Priyadarshini; Rosario, Fredrick J; Weintraub, Susan T et al. (2016) Down-Regulation of Placental Transport of Amino Acids Precedes the Development of Intrauterine Growth Restriction in Maternal Nutrient Restricted Baboons. Biol Reprod 95:98
Jansson, Thomas (2016) Placenta plays a critical role in maternal-fetal resource allocation. Proc Natl Acad Sci U S A 113:11066-11068
Dimasuay, Kris Genelyn; Boeuf, Philippe; Powell, Theresa L et al. (2016) Placental Responses to Changes in the Maternal Environment Determine Fetal Growth. Front Physiol 7:12
Schlabritz-Loutsevitch, Natalia; Gygax, Scott E; Dick Jr, Edward et al. (2016) Vaginal Dysbiosis from an Evolutionary Perspective. Sci Rep 6:26817
Schlabritz-Loutsevitch, Natalia E; Comuzzie, Anthony G; Mahaney, Michael M et al. (2016) Serum Vitamin D Concentrations in Baboons (Papio spp.) during Pregnancy and Obesity. Comp Med 66:137-42

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