Influence of Maternal Exercise on Infant Skeletal Muscle and Metabolomics

The American Heart Association suggests that heart disease prevention should target pregnancy
and the first year of life; however, there is a fundamental gap in knowledge regarding the
effects of prenatal exercise on the prevention of heart disease.[1, 2] Insulin resistance in
skeletal muscle is believed to be a critical contributor to the metabolic syndrome which
increases the risk for cardiovascular disease (CVD). Conversely, exercise improves insulin
sensitivity and many other facets of skeletal muscle function and metabolism; however, it is
unclear if this positive effect can be "imprinted" in the skeletal muscle of the fetus with
maternal exercise and accordingly diminish CVD risk in offspring. Our previous studies found
that exercise during pregnancy leads to improved heart measures and reduced adiposity.[3-6]
These studies demonstrated the potential for maternal exercise to reduce risk for CVD, but
the cellular mechanisms involved, however, are not clearly evident. The proposed project will
fill this critical gap and assess the influence of maternal exercise intervention to
"imprint" progenitor stem cells in the fetus (umbilical cord tissue) to develop into insulin
sensitive skeletal muscle and also improve indices of infant morphometry and movement. Using
a randomized design, 160 women will perform either exercise intervention (aerobic training,
resistance training, or both) or usual care (controls). Infant cord tissue and blood will be
sampled at birth while blood will be sampled at 1 month of age. Similarly, infant neuromotor
and morphometric examinations will be performed at 1 month. and at 1-month of age via blood
sample, neuromotor, and morphometric examinations. The rationale for the project is to
elucidate the effects of maternal exercise on offspring health outcomes and determine
specific metabolic targets predictive of offspring long-term disease risk. The investigators
will test the central hypothesis that exercise during pregnancy alters skeletal muscle in a
manner which decreases the risk of heart disease in offspring. To test this central
hypothesis, the investigators will pursue two specific aims: Aim 1- Determine the ability of
regular maternal exercise to imprint key myocellular metabolic (insulin sensitivity)
properties of offspring mesenchymal stem cells (MSC), neuromotor function, and morphometry.
Aim 2- Determine the distinct abilities of regular maternal exercise to imprint the
metabolome of offspring MSC.