Pre-eclampsia (PE) is a serious complication affecting 1 in 12 pregnancies, defined by new-onset hypertension and proteinuria after 20 weeks of gestation. Annually, PE claims the lives of 76,000 mothers and 500,000 babies, making it the world’s deadliest pregnancy complication. Early detection of PE is key for appropriate clinical decision-making throughout pregnancy to reduce life threatening complications. Extracellular vesicles (EVs) are important circulating messengers regulating a myriad of biological and pathological processes and may be highly relevant to the pathophysiology of PE. We hypothesise that EVs circulating in the first trimester contain markers that may potentially predict occurrence of PE.
Ethical approval was gained to access the Biological Resource Bank in the Coombe Women and Infants University Hospital Dublin. Early pregnancy (11-15 weeks) plasma samples from healthy women (n=67) and women who subsequently went on to develop a confirmed diagnosis of PE during their pregnancy (n=27) were randomly selected from the biobank . Circulating EV particle concentration and size was determined using Nanoparticle Tracking Analysis and flow cytometry.
We observed a trend towards an increase in particles in the size range of 30-400 nm in the plasma of women who went on to develop PE relative to control patients from 11 weeks of gestation. Comparative proteomic analysis of EVs revealed a number of proteins significantly altered between the groups, which we confirmed using ELISA.
We have found differential levels of circulating vesicles and secreted proteins in plasma of expectant mothers who went on to develop PE. Such anomalies identified at this crucial early stage of pregnancy when the placenta becomes definitive and takes over from the yolk sac, may underpin aberrant placental implantation and future pregnancy complications. Our results may provide clinicians with the much-needed tools to identify women at future risk of PE.
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