Abstract

Successful placental development is crucial for optimal growth, maturation, and survival of the embryo/fetus. Placental failure and placental pathology contributes to both morbidity and mortality of the fetus. We sought to understand normal placental development and also placental responses to stress using oligonucleotide microarray technology. To examine genetic aspects of normal placental development, we investigated gene expression patterns in the murine placenta at embryonic day 10.5 (E10.5), E12.5, E15.5, and E17.5. Hypoxia has been identified as a major stressor in placental and fetal development. In order to comprehend more completely hypoxic stress responses we sought to measure gene expression changes in the mouse placenta in response to 48 hours of hypoxia from E15.5 to 17.5. Also, maternal protein restriction has been shown to have deleterious effects on placental development and has long term consequences for the progeny. In order to examine stress responses to maternal protein restriction, we sought to measure gene expression changes in the mouse placenta in response to 7 days of protein restriction from E10.5 to E17.5. Angiogenesis and fatty acid metabolism and transport related genes were up-regulated at E10.5, while genes involved in hormonal control and ribosomal proteins were up-regulated at E12.5. Genes involved in the cell cycle and RNA metabolism were up-regulated at E12.5, while genes involved in cellular transport were up-regulated at E15.5. Genes related to cell cycle control, genes expressed in the nucleus and involved in RNA metabolism were up-regulated at E17.5. We observed that hypoxia up-regulated proteins involved in reactive oxygen species metabolism and DNA methylation enzymes. Also, apoptosis related genes were upregulated. In response to protein deprivation negative regulators of cell growth and metabolism in conjunction with genes involved in epigenesis were up-regulated. The presence of epigenetic regulating proteins suggests that hypoxia and protein deprivation may contribute to growth restriction and long-term epigenetic changes in stressed tissues and organs.

LLU Discipline

Physiology

Department

Physiology

School

Graduate Studies

First Advisor

Lawrence D. Longo

Second Advisor

Subburaman Mohan

Third Advisor

Kerby C. Oberg

Fourth Advisor

Steven M. Yellon

Degree Name

Doctor of Philosophy (PhD)

Degree Level

Ph.D.

Year Degree Awarded

2006

Date (Title Page)

9-2006

Language

English

Library of Congress/MESH Subject Headings

Fetus -- physiology; Placenta -- physiology; Placenta -- growth and development; Gene Expression Regulation, Developmental; Fetal Hypoxia -- physiopathology; Maternal Nutrition Physiology -- genetics

Type

Thesis

Page Count

vii; 98

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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