It is not commonly understood that renal disease is a major cause of cardiovascular disease. Thus,understanding how challenges during development affect the kidney is very important. It has been shown that maternal undernutrition decreases the number of effective tubules that concentrate our urine, and therefore the kidney is impaired at birth in both the undernourished and the over nourished fetus.
TPLH has assembled a colony of baboons that currently contains 188 animals between 0 and 25 years of age (0 to 100 human equivalent). In addition to studies on postnatal animals across the life-course, the TPLH NICHD P01, in year 22, supports studies on mothers and their fetuses throughout pregnancy. Several well-established, funded investigator groups are collaborating in either individual projects or multidisciplinary, multi-institution projects studying these animals.
We have considerable experience in conducting long-term in vivo physiological studiesusing free moving animals on a tether system to study endocrine, cardiovascular, and metabolic endpoints. We have an extensive archive of frozen and fixed brain tissues from fetuses and pregnant baboons from 0.5 gestation to term and across the life-course.
We are developing a multi-institution, multidisciplinary project to develop the power of this unique nonhuman primate colony to evaluate effects of the following on kidney development and function:
- health of mothers and sires before pregnancy;
- outcomes of developmental programming challenges, such as sub-optimal maternal nutrition (under- and over-nutrition), maternal stress, and exposure to environmental pollutants and obstetric pharmacological agents administered to mothers in pregnancy and lactation;
- normal life course aging.
Pereira SP, Oliveira PJ, Tavares LC, Moreno AJ, Cox LA, Nathanielsz PW, Nijland MJ. (2015) Effects of moderate global maternal nutrient reduction on fetal baboon renal mitochondrial gene expression at 0.9 gestation. Am J Physiol Renal Physiol 308(11):F1217-1228. PMID 25761880.
Li, C., Ramahi, E., Nijland, M.J., Choi, J., Myers, D.A., Nathanielsz, P.W., McDonald, T.J. (2013) Up-regulation of the Fetal Baboon Hypothalamo-Pituitary-Adrenal Axis in Intrauterine Growth Restriction: Coincidence with Hypothalamic Glucocorticoid Receptor Insensitivity and Leptin Receptor Down-regulation. Endocrinology 154: 2365-2373. PMID 23625543.
Long, N., Ford, S., Nathanielsz, P. (2012) Multigenerational effects of fetal dexamethasone exposure on the hypothalamic-pituitary-adrenal axis of first and second generation female offspring. AJOG 208(3): 217. PMID 23220271.
Long, N.M., Nathanielsz, P.W., Ford, S.P. (2012) The impact of maternal overnutrition and obesity on hypothalamic-pituitary-adrenal axis response of offspring to stress. Domest Anim Endocrinol 42(4): 195–202. PMID 22264661.
Nijland MJ, Schlabritz-Loutsevitch N, Hubbard GB, Nathanielsz PW, Cox LA. (2007) Nonhuman Primate Fetal Kidney Transcriptome Analysis Indicates mTOR is a Central Nutrient Responsive Pathway. J Physiol 579: 643-656. PMID 17185341.
Cox, L.A., Nijland, M.J., Gilbert, J.S., Schlabritz-Loutesevitch, N.E., Hubbard, G.B., McDonald, T.J., Shade, R.E., Nathanielsz, P.W. (2006) Effect of thirty percent maternal nutrient restriction from 0.16 to 0.5 gestation on fetal baboon kidney gene expression. J Physiol 572:67-85. PMID 16513668.