TPLH baboons undergo magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and ultrasonography, state of the art techniques for assessing organ development and function in humans. Imaging biomarkers can yield evidence of specific anatomical sites that exhibit abnormal morphological and functional traits. Association of measured symptoms with phenotypes derived from imaging studies provides insights for investigations into the mechanisms of action following developmental programming. Since this is the same testing protocol and equipment used in humans of all ages, a major advantage of our approach is findings are highly translatable from nonhuman primates to humans. This will lead to improved prediction of cognitive and physiological outcomes of developmental programming, an essential step for formulation of therapeutic interventions.
Some of our most exciting findings thus far have been in a cohort of baboons born with intrauterine growth restriction (IUGR) due to low maternal nutrition during pregnancy and lactation. IUGR is a common and persistent problem in humans. We have used MRI, MRS, and ultrasonography in adult IUGR-born baboons to show life-long consequences, including myocardial remodeling and reduced systolic and diastolic function (see figure);1 premature brain aging;2 premature cardiovascular aging;3 impaired function of the aorta;4 changes in artery sizes, distensibility, and blood flow;5 and abnormal right6 and left7 ventricular function.
Our imaging work demonstrates that profound changes to structure and function of the brain and heart result from poor maternal nutrition and persist into adulthood, causing premature aging and predisposition to disease.
- Kuo AH, Li C, Li J, Huber HF, Nathanielsz PW, Clarke GD. Cardiac remodelling in a baboon model of intrauterine growth restriction mimics accelerated ageing. J Physiol (Lond). 2017;595(4):1093–1110. PMID: 27988927
- Franke K, Clarke GD, Dahnke R, Gaser C, Kuo AH, Li C, Schwab M, Nathanielsz PW. Premature brain aging in baboons resulting from moderate fetal undernutrition. Front Aging Neurosci. 2017;9:92. PMID: 28443017
- Kuo AH, Li C, Huber HF, Nathanielsz PW, Clarke GD. Aging changes in biventricular cardiac function in male and female baboons (Papio Sp.). Journal of Physiology. In press. PMID: 30144074
- Kuo AH, Li J, Li C, Huber HF, Nathanielsz PW, Clarke GD. Poor perinatal growth impairs baboon aortic windkessel function. J Dev Orig Health Dis. 2018;9(2):137–142. PMID: 29017630
- Kuo AH, Li C, Huber HF, Clarke GD, Nathanielsz PW. Intrauterine growth restriction results in persistent vascular mismatch in adulthood. J Physiol (Lond). 2017 Nov 3;In press. PMID: 29098705
- Kuo AH, Li C, Huber HF, Schwab M, Nathanielsz PW, Clarke GD. Maternal nutrient restriction during pregnancy and lactation leads to impaired right ventricular function in young adult baboons. J Physiol. 2017;595(13):4245–4260. PMID: 28439937
- Clarke GD, Li J, Kuo AH, Nathanielsz PW. TU-F-CAMPUS-I-03: Quantitative cardiac MRI reveals functional abnormalities in intrauterine growth restricted (IUGR) baboons. Med Phys. 2015 Jun 1;42(6):3646–3647.