Collaborative Research: Effects of Developmental Hypoxia on Juvenile Cardiac Function

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This collaborative project will investigate the outcome of low environmental oxygen levels (hypoxia) experienced during early development on the cardiovascular system of the American alligator, a species that naturally experiences low oxygen during embryonic life. The cardiovascular system is essential for the distribution of oxygen and metabolic fuels to active tissues. In some developing vertebrates, including humans, the function of the immature cardiovascular system can be negatively affected by environmental challenges such as low oxygen, and these changes can adversely affect the health of the adult. By contrast, species that naturally experience low oxygen during development, such as alligators, can benefit later in life from the changes to the cardiovascular system resulting from developmental hypoxia. Cardiovascular function will be assessed in two-year-old juvenile American alligators that were exposed to hypoxia as embryos, under active conditions (while exercising and after feeding). An integrative assessment will be conducted from the level of individual proteins to that of the whole animal. The broader impacts of the project include a significant number of opportunities for training students at multiple education levels in skills relevant to biomedical research, which will have a direct impact on the future work force, and training and practice in communicating science to the public. Developmental plasticity is a phenomenon that enables multiple environmentally mediated phenotypes to be generated from a single genotype. This plasticity, which is present in all multicellular taxa, can result in beneficial or adaptive changes that enhance function during juvenile and adult life. Hypoxia is an ecologically relevant environmental condition that, if encountered during embryonic life when organ systems are developing, can result in altered juvenile phenotypes that can impact organismal performance and affect animal fitness. Despite the important role hypoxia plays in causing phenotypic change, fundamental questions remain regarding the long-term effects of developmental hypoxia in vertebrates. This project investigates the impact of hypoxia experienced during a critical period of development on cardiovascular function of juvenile alligators at multiple levels of biological organization: from whole-animal performance, to functional studies of the cardiovascular system, to the organ, cellular, protein, and gene levels of organization. Alligators will be studied because they can naturally experience hypoxia during development and as adults. This approach will establish links between molecular and cellular traits, including changes in expression of genes involved in calcium dynamics and in cardiomyocyte contractility that underpin differences in cardiac output at the whole organism level. This multi-level approach will provide a comprehensive understanding of how embryonic hypoxia impacts cardiovascular function, with applicability to other vertebrate systems. The research findings will provide basic information that will be needed to make informed animal management decisions in the era of global climate change, and could lead to future treatment options for cardiovascular disease states. The project involves research training of graduate students and undergraduate students recruited from groups under-represented in science, as well as outreach to K-12 students and the general public.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.