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 #
5P01HD021350-18
Application #
7669279
Study Section
Special Emphasis Panel (ZHD1-MCHG-B (PN))
Program Officer
Ilekis, John V
Project Start
1997-04-01
Project End
2012-07-31
Budget Start
2009-08-01
Budget End
2010-07-31
Support Year
18
Fiscal Year
2009
Total Cost
$1,520,903
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
Kuo, Anderson H; Li, Cun; Huber, Hillary F et al. (2018) Ageing changes in biventricular cardiac function in male and female baboons (Papio spp.). J Physiol 596:5083-5098
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

Showing the most recent 10 out of 268 publications