Speakers - 2026

Title: Extracellular DNA and its clearence in preeclampsia

Abstract

Preeclampsia is a serious pregnancy complication threatening the mother and the child and an unknown etiology. Higher concentrations of extracellular DNA (ecDNA), especially fetal ecDNA, have been consistently reported in preeclampsia and may contribute to disease pathogenesis rather than merely reflect ongoing tissue damage. As deoxyribonucleases (DNases) are responsible for ecDNA degradation, we hypothesized that the higher ecDNA concentrations observed in preeclampsia would be associated with lower DNase activity.

Plasma samples from women with preeclampsia and healthy pregnant controls were analyzed in three independent cohorts. Total ecDNA concentrations and fetal ecDNA were quantified using quantitative real time PCR. DNase activity was assessed using commercial probe-based kits.. Differences between groups were evaluated.

Women with preeclampsia had significantly higher concentrations of both total and fetal ecDNA than healthy pregnant controls, confirming previous observations. Contrary to our hypothesis, DNase activity was also significantly higher in preeclampsia. This finding was consistent across all three independent cohorts despite differences between centers.

The coexistence of higher ecDNA and higher DNase activity suggests that impaired DNA degradation is unlikely to be the primary cause of ecDNA accumulation in preeclampsia. Elevated DNase activity may represent a compensatory response to excessive ecDNA release from placental and maternal tissues. Further studies are needed to elucidate the mechanisms underlying this unexpected association and to determine whether altered ecDNA turnover contributes to the pathogenesis of preeclampsia.

What will the audience take away from presentation?

• Rethinking Preeclampsia Pathophysiology: The audience will learn that ecDNA accumulation in preeclampsia is not caused by a deficit in enzymatic clearance (DNase activity), shifting the focus toward production and release mechanisms.
• Discovery of a Compensatory Mechanism: Counter to intuitive hypotheses, the presentation demonstrates that DNase activity increases alongside ecDNA, likely as an adaptive maternal-fetal response to tissue stress.
• Robust Multi-Center Validation: Researchers will see the value of testing hypotheses across multiple independent cohorts, proving that these molecular trends are robust and not center-specific.
• Inspiration for Future Biomarker Design: Faculty and clinical researchers can utilize these insights into ecDNA turnover to design new diagnostic tools or investigate how kinetic clearance rates (rather than static levels) impact pregnancy pathologies.