Date of Award

Spring 5-15-2017

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Developmental, Regenerative, & Stem Cell Biology)

Degree Name

Doctor of Philosophy (PhD)

Degree Type



The developmental origins of health and disease (DoHAD) hypothesis suggests that negative maternal lifestyle choices, such as obesity, affect the health of her offspring. Clinical and laboratory studies support this hypothesis – offspring born to obese mothers are at increased risk for health conditions including cardiometabolic syndrome and congenital abnormalities. Maternal obesity damages the oocytes, contributing to the increased disease risk by transmitting damaged organelles and epigenetic modifications to the offspring. Mitochondria, the most abundant organelle in the oocyte, are damaged in oocytes from obese females. However, we do not understand if mitochondrial damage in oocytes is reversible nor why offspring are at increased risk for cardiometabolic syndrome like cardiomyopathy. Here we show that in mice fed a high fat/high sugar (HF/HS diet), improving female health with moderate, voluntary exercise does not reverse oocyte damage. We also tested if oocytes could activate mitophagy to repair obesity induced mitochondrial damage. Finally, we show that female offspring from obese mothers have mitochondrial damage in the heart that persists into adulthood. This damage causes dilated cardiomyopathy that worsens with age. These results provide an explanation for the persistence of damaged mitochondria in the oocytes of obese females. Additionally, they suggest that maternal obesity promotes the development of heart failure in offspring by inducing mitochondrial damage in the heart. Together, this data suggests mitochondrial damage caused by maternal obesity is non-reversible and contributes to cardiometabolic syndrome. The research provides potential mechanisms that support the DoHAD hypothesis and open new questions about how the changes to offspring health occur.


English (en)

Chair and Committee

Kelle H. Moley

Committee Members

Joan Riley, James Skeath, Tim Schedl, Jennifer Duncan,


Permanent URL: https://doi.org/10.7936/K7QZ28DV