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Ericka M. Biagioni, Nicholas T. Broskey. East Carolina University, Greenville, NC.

BACKGROUND: The prevalence of gestational diabetes mellitus (GDM) is increasing, and offspring exposed to GDM in utero have an increased risk of long-term health consequences. Exercise has been shown to ameliorate conditions associated with metabolic dysfunction in part via improvements in mitochondrial function. Current data in rodent models of pregnant dams suggest these mitochondrial outcomes can be transferred from the mother to the developing fetus through exercise. However, when lifestyle modifications are not sufficient to treat GDM, metformin is commonly prescribed. Metformin freely crosses the placenta and reaches concentrations in fetal circulation that are equal to that of maternal circulation. Like exercise, metformin also elicits effects on the mitochondria by decreasing efficiency via decreases in the net proton motive force. Metformin has been shown to attenuate the mitochondrial adaptations from exercise when combined; however, this has not been tested in pregnancy. Umbilical cord derived mesenchymal stem cells (MSCs) give rise to several tissues originating from the fetal mesoderm and serve as a robust model of offspring cellular outcomes. The purpose of this study is to investigate the impact of in vitro metformin exposure on mitochondrial outcomes in MSCs that are from healthy women, who exercise or are exposed to metabolic disease in utero. METHODS: MSCs will be cultured from umbilical cord Wharton’s Jelly from pregnant women who were sedentary, exercised, or diagnosed with GDM and not on metformin. Cells from each group will be treated with media conditions containing metformin and without. Mitochondrial efficiency will be measured in permeabilized MSCs through a series of mitochondrial diagnostic assays that will measure the rate of oxygen consumption (JO2) and/or the rate of ATP generation (JATP) with the addition of various substrates, enzymes, and inhibitors. Statistical analysis will be performed in GraphPad Prism by using two-way ANOVA and presented as mean + SEM to determine differences between groups. ANTICIPATED RESULTS: We hypothesize that MSCs from sedentary, exercised, and GDM pregnancies that are treated with metformin in vitro will have lower mitochondrial efficiency compared to those not exposed to metformin within each respective group. These results will lead to further investigation into the impact of metformin treated GDM on offspring mitochondrial outcomes.

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