Intergenerational Effects of Maternal Obesity on Offspring Mitochondrial Reactive Oxygen Species Production and DNA Damage


Epidemiological studies have shown that offspring from pregnancies
complicated by maternal obesity have a 4-fold greater risk for developing childhood
obesity and symptoms of metabolic syndrome. The developmental origins of health and
disease (DOHaD) hypothesis states that certain environmental exposures during critical
windows of development may have consequences for an individual’s long term health.
DOHaD may explain a portion of the continual increase in obesity rates among
children. In a nonhuman primate model, offspring of obese dams become sensitized to
obesity-induced metabolic disruptions, including insulin resistance and mitochondrial
disfunction. Increased reactive oxygen species (ROS) production contributes to
mitochondrial defects observed in obesity. Oxidative stress, which is caused by
overproduction of ROS, can lead to mitochondrial DNA (mtDNA) mutations, decreased
copy number, reduced membrane permeability and subsequent suppression of
mitochondrial respiratory chain activity. Therefore, I hypothesize that maternal obesity
increases offspring mitochondrial ROS production leading to mtDNA damage without
loss of mtDNA abundance. To study the effect of maternal obesity, we used a previously established Japanese macaque model of fetal programming. Dams were fed
either a control (CON) diet or western style diet (WSD) prior to and during pregnancy
and lactation. Offspring were then weaned at 8 months and fed a healthy CON diet.
Skeletal muscle biopsies from offspring were collected at 3 years of age and relative
mtDNA abundance was measured using quantitative PCR (qPCR) amplification of short
regions of mtDNA. No differences were measured in the amount of mtDNA between
offspring groups. Similarly, no differences were measured in the amount of mtDNA
damage between offspring groups. Overall, these data indicate that exposure to maternal
obesity and WSD during fetal development does not reduce mitochondrial abundance or
alter mitochondrial homeostasis that is linked to ROS production in skeletal muscle of
adolescent offspring.


28 pages. A thesis presented to the Department of Human Physiology and the Clark Honors College of the University of Oregon in partial fulfillment of the requirements for degree of Bachelor of Science], Winter 2021.

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