In addition to cord blood resistin concentration being higher in pregnancies complicated by diabetes, a positive correlation with maternal blood glucose levels was found. Hyperglycemia and hyperinsulinemia in GDM are known to activate inflammatory cells and induce a pro-inflammatory status (Pantham et al. 2015). In accord, we found that cord blood mononuclear cells secreted resistin in response to exposure to high glucose and other diabetes-related factors. Thus, our findings further characterize resistin as an inflammatory cell-derived factor that responds to hyperglycemia and metabolic stresses associated with diabetic pregnancy. Our study begins to examine potential functions of resistin in the fetus, suggesting involvement in regulation of placental mitochondrial abundance and function. Mitochondria play a key role in placental function, and defects in placental mitochondrial function and content are associated with impaired placental energetics and increased oxidative stress, which lead to adverse pregnancy outcomes (Mando et al. 2018; Clemente et al. 2017; Bijnens et al. 2019). We previously demonstrated a decrease in PGC-1α/TFAM/mitochondrial biogenesis signaling in placenta of women with diabetes during pregnancy (Jiang et al. 2017). Here we observed decreases in PGC-1α expression and mitochondrial DNA copy number when human placental explants were exposed to resistin. In addition, resistin treatment reduced the abundance of pyruvate dehydrogenase (PDH) and ATP production. Pyruvate dehydrogenase is a mitochondrial enzyme that catalyzes pyruvate oxidation, linking glycolysis to the Krebs cycle for ATP generation to meet energy demands (Park et al. 2018). Mitochondria are the primary source of ATP needed for placental growth, nutrient transport, and hormone synthesis. Therefore, increased expression of resistin may contribute to impaired placental mitochondrial biogenesis and function, as well as offspring adverse outcomes in pregnancies complicated by diabetes.