Electronic Thesis and Dissertation Repository

Degree

Master of Science

Program

Physiology and Pharmacology

Supervisor

Dr. Bryan Richardson

Abstract

Maternal nutrient restriction (MNR) in guinea pigs results in placental structural abnormalities that reduce nutrient transport contributing to fetal growth restriction (FGR). However, whether brain weights are similarly reduced, or preserved by “brain sparing” mechanisms, and whether energy levels are depleted leading to membrane failure and overt injury remains unknown. Guinea pig sows were fed ad libitum (Controls) or 70% of the control diet pre-pregnant switching to 90% at mid-pregnancy (MNR). Animals were necropsied near term for fetal growth measures and fetal brains were assessed for markers of necrotic cell injury, apoptotic cell injury, endoplasmic reticulum stress, and altered development proteins. MNR resulted in FGR with brains that are large relative to body weight and livers that are small relative to body weight, which suggests a degree of blood flow redistribution. These fetuses have reduced brain weights, but with substantial brain sparing, and with no increased necrotic cell injury and no changes in synaptic development, indicating that the threshold for membrane failure or aberrant development with energy depletion has likely not been reached. However, apoptotic indices were increased in FGR-MNR cohort compared to appropriate for gestational age (AGA)-control cohort and more so in males than females. Changes in apoptosis were primarily in hippocampal regions and were not accompanied by significant changes of protein levels of investigated pro-apoptotic factors.

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