, a pregnancy-specific syndrome, is associated with maternal systemic and placental inflammatory responses. Cell-free DNA
(cfDNA) and cf-foetal DNA (cffDNA) in the blood are elevated in patients with preeclampsia
and act as danger signals. Placenta
-derived foetal DNA induces inflammatory responses and pregnancy complications in mice. However, whether extracellular DNA from the placenta
really causes inflammatory responses remains unclear. Therefore, we investigated the effect of serum cfDNA and placental cffDNA on inflammatory responses using normal pregnant women and preeclampsia
Sera were taken from normal pregnant women and preeclampsia
patients, and human trophoblast cell line Sw.71 cells were treated with serum with or without toll-like receptor 9 (TLR9; a sensor of exogenous DNA) inhibitor and genome elimination reagent. For cffDNA collection, placental tissue from the participants was cultured, and the released cffDNA was administrated to Sw.71 cells.
The amount of serum cfDNA was higher in preeclampsia
patients than in normal pregnant women. Treatment of preeclampsia
serum stimulated inflammatory cytokine secretion, which was inhibited by a genome elimination reagent. Expression levels of TLR9 and amount of cffDNA from the placenta
were higher in preeclampsia
patients than of normal pregnant women. Preeclampsia
-derived cffDNA increased inflammatory cytokine levels compared with normal pregnant derived cffDNA.
In human trophoblast cells, preeclampsia
patient-derived cfDNA increased inflammatory cytokine levels via TLR9. Preeclampsia placenta
released more cffDNA, which stimulated inflammatory cytokine. We suggest that elevated circulating cfDNA and cffDNA induces placental inflammatory responses, resulting in accelerated pathological features of preeclampsia