Exosome Profiles for Normal and Complicated Pregnancies—A Longitudinal Study [3O

Abstract

INTRODUCTION: Exosomes are small nanovesicles which play a key role in cell-to-cell communication during pregnancy by transferring bioactive molecules to other cells and modifying their biological functions. Little is known about the changes in the concentration of circulating exosomes throughout gestation in normal and complicated pregnancies. METHODS: A prospective cohort of patients approved by IRB was recruited during pregnancy and retrospectively stratified based on normal (n=30), gestational diabetes mellitus (GDM) (n=10) and preeclampsia (PE) pregnancy outcomes (n=15). Total exosomes and specific placental-derived exosomes (PdE) were determined by Nanoparticle Tracking Analysis using quantum dots coupled with CD63 or PLAP antibodies. Linear mixed modeling was performed on normalized total and PdE across gestation using the lme4 package in R. Using likelihood ratio tests, statistically significant differences were found in exosome concentration across gestation. RESULTS: Significant factors contributing to variations in total and PdE were gestational age and pregnancy outcomes (ANOVA, p<0.05). Post-hoc analyses established that PdE concentrations increased during gestation in normal, GDM and PE pregnancies. The increase was significantly greater in GDM and PE compared with normal pregnancies. Our linear mixed modeling analysis showed that PdE increased ∼2.1-fold in PE and GDM compared to normal through gestation. Interestingly, maternal BMI, glucose concentration and fetal weight significantly affect the concentration of PdE across gestation. CONCLUSION: This study provides evidence of the changes exosomes present in maternal circulation across gestation, suggesting that exosomes may be involved in maternal metabolic adaptation to pregnancy. Further, exosomes can be an early predictor of adverse outcomes, including GDM and PE.