Abstract

The prenatal environment plays a major role in influencing the health of adult offspring. Maternal food restriction (MFR) during pregnancy is a common stressor that correlates to long-term consequences, including increased risk of cardiovascular and metabolic diseases in adult offspring. Numerous studies report persistent changes following MFR, with an emphasis on the heart and kidney. These consequences are thought to occur via programming, in which a stressor, during critical developmental windows, permanently alters the structure and function of selective fetal tissues. Furthermore, the elevation of maternal glucocorticoids associated with intrauterine stressors is a proposed mechanism of several programming events, including MFR. Although cerebral blood vessels in the context of MFR and glucocorticoids are understudied, our group recently showed that adult rat cerebrovasculature is negatively altered by MFR. The existence of comorbidities, such as obesity and hypertension, in MFR adult rats led us to develop a mild hypoxic-ischemia (HI) injury model to test cerebrovasculature responses in non-obese and normotensive MFR neonates. Our first study examined the role of gestational glucocorticoids alone on neonatal cerebrovasculature and HI vulnerability. Four groups of Sprague-Dawley neonates were included: 1) Untreated-Sham; 2) MET-Sham; 3) Untreated-HI; 4) MET-HI. Metyrapone

(MET), a corticosteroid synthesis inhibitor, was administered via drinking water from gestational day 11 to term in rats fed an ad libitum diet. The second study examined the role of MFR and gestational glucocorticoids on neonatal cerebrovasculature and HI vulnerability. Four groups of Sprague-Dawley MFR neonates were studied: 1) Untreated-Sham; 2) MET-Sham; 3) Untreated-HI; 4) MET-HI. At day 10 of gestation, MFR rats, in a pair-fed model, underwent 50% caloric restriction. MET was administered via drinking water from gestational day 11 to term. These studies demonstrate that both changes to nutrition and glucocorticoid levels during gestation differentially impact basal physiology and responses to HI injury in neonates. Future studies will further investigate the role of MFR on cerebral and cerebrovasculature structure as well as probe into the role of epigenetic regulation on cerebrovasculature function.

LLU Discipline

Physiology

Department

Physiology

School

School of Medicine

First Advisor

William J Pearce

Second Advisor

Erik Behringer

Third Advisor

Eugenia Mata-Greenwood

Fourth Advisor

Andre Obenaus

Fifth Advisor

Lubo Zhang

Degree Name

Doctor of Philosophy (Medical Science)

Degree Level

Ph.D.

Year Degree Awarded

2020

Date (Title Page)

12-2019

Language

English

Library of Congress/MESH Subject Headings

Glucocorticoids; Metyrapone; Caloric Restriction; Pregnancy -- physiology

Type

Dissertation

Page Count

xiv, 143 p.

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

Download

Included in

Physiology Commons

Share

COinS