Date of Award

1-1-2025

Degree Type

Dissertation

Degree Name

Doctor of Philosophy in Biological and Environmental Sciences

Department

Fisheries, Animal and Veterinary Science

First Advisor

Maria L. Peterson

Abstract

Maternal nutrition plays an important role in shaping offspring health through developmental programming, with lasting implications on metabolic function and disease susceptibility. This dissertation explores the molecular and physical consequences of maternal nutrition, particularly its effects on pancreatic development and function in offspring. Chapter one provides a comprehensive review of the literature, detailing the mechanisms of fetal development, epigenetic regulation, and metabolic programming. It highlights the thrifty phenotype hypothesis, the role of DNA methylation and histone modifications, and the impact of maternal nutrition, emphasizing how nutrient availability during pregnancy influences fetal organogenesis and long term metabolic health.

Chapter two examines maternal obesity and its epigenetic effects on offspring pancreatic function in mice. This chapter focuses on DNA methylation as a key regulatory mechanism. Findings indicate that maternal high-fat diet (HFD) consumption leads to hypermethylation of genes associated with pancreatic β-cell function, reducing insulin secretion and increasing the risk of metabolic dysfunction in the offspring. These sex specific epigenetic modifications further highlight the complexity of maternal nutritional influences on fetal metabolic programming. Expanding on this, chapter three investigates proteomic alterations within those same tissues, revealing downregulation of proteins involved in insulin signaling and glucose metabolism. The study identifies sex-specific vulnerabilities, with male offspring showing greater reductions in proteins essential for β-cell survival, reinforcing the long term consequences of maternal dietary excess on pancreatic function.

Chapter four extends these findings by examining the impact of maternal nutrition on proteomic expression patterns in an ovine model, illustrating how both maternal overnutrition and undernutrition has the potential to alter key metabolic stress related proteins. Lastly, chapter 5 explores metabolic shifts in nutrient restricted dams, focusing on the role of one carbon metabolism (OCM) supplementation in restoring maternal metabolic balance. The findings demonstrate that OCM interventions improve methylation capacity and maternal metabolic function, offering a potential strategy to mitigate the adverse effects of maternal nutrient restriction.

Together these chapters provide a comprehensive analysis of how maternal nutrition influences fetal metabolic programming through epigenetic, proteomic, and metabolic pathways. These findings underscore the critical importance of optimizing maternal diet to improve offspring metabolic health with implications for human health, livestock management, and future therapeutic strategies aimed at reducing developmental programming induced metabolic disorders.

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