Date of Completion

1-17-2017

Embargo Period

1-16-2017

Keywords

maternal nutrition, sheep, mesenchymal stem cells, organs, muscle

Major Advisor

Dr. Kristen E. Govoni

Associate Advisor

Dr. Steven Zinn

Associate Advisor

Dr. Steven A. Zinn

Associate Advisor

Dr. Sarah A. Reed

Associate Advisor

Dr. Rachel O’Neill

Field of Study

Animal Science

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

Poor maternal nutrition during gestation can lead to intrauterine growth restriction resulting negative impacts on the growth development and metabolism of the offspring. Specifically, poor maternal nutrition during gestation will lead to a reduction in muscle and bone content, increase adiposity and alter organ development in offspring. Although studies have elucidated the impacts of poor maternal nutrition on multiple tissues at different time points in the life of offspring, the potential mechanisms behind these alterations need to be studied in detail. We hypothesized that maternal under- and over-nutrition during gestation in sheep will 1) alter the development of muscle, bone, adipose and vital organs in offspring 2) impact the proliferation, differentiation, and metabolism of mesenchymal stem cells (MSC) and 3) alter the expression of key genes and novel pathways involved in the prenatal muscle. To test these hypotheses, two independent in-vivo experiments were conducted using sheep as a model. In the first study, thirty-six pregnant ewes were individually housed and randomly assigned to one of three diets (100%, 60%, or 140% of National Research Council (NRC) requirements for TDN) at d 31 ± 1.3 of gestation. Lambs from these ewes were euthanized within 24 hours of birth and 3 months of age to obtain samples to conduct further studies. Maternal diet negatively affected offspring MSC by reducing proliferation 50 % and reducing mitochondrial metabolic activity (P ≤ 0.04). In the second in-vivo study, eighty-two pregnant ewes were individually housed and randomly assigned to one of three diets (100%, 60%, or 140% of NRC requirements for TDN) at d 30 ± 0.2 of gestation. Lambs from these ewes were euthanized at different time points of gestation and at birth to obtain the samples to conduct further studies. Although no significant interactions of diet by day of gestation and main effect of poor maternal nutrition were observed for fiber CSA of Longissimus muscle, semitendinosus (STN), and triceps brachii (TB) (P ≥ 0.28), there was a significant main effect of time on the fiber CSA of LM, STN, and TB (P ≤ 0.0001). Samples from longissimus dorsi were used to perform transcriptome analysis to evaluate the differential gene expression. Data from transcriptome analysis found alterations in the expression of genes involved in epigenetic regulation and cell signaling as a result of exposure to poor maternal nutrition (q ≤ 0.05). In conclusion, poor maternal nutrition affects the growth and development of organs, adipose and muscles through different mechanisms. The potential mechanisms that were identified as a part of these studies were alterations in the gene expression and stem cell functions. Future studies are needed to identify the role of epigenetic modifications as a potential mechanism behind the observed impacts of poor maternal nutrition in offspring.

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