sFlt-1 in Decidua, Placenta, and Maternal Serum in Preeclampsia Subtypes

Soluble FMS-like tyrosine kinase (sFlt-1) drives maternal symptoms in preeclampsia, serves as a predictive biomarker, and represents a promising therapeutic target. sFlt-1 is expressed in placental and decidual tissue, which together form the maternal-fetal interface. Whether placental and decidual expression of sFlt-1 regulates the maternal serum levels remains unknown. This study aimed to investigate sFlt-1 expression and co-regulation in decidua, placenta, and maternal serum, in normal pregnancies and preeclamptic pregnancies with and without fetal growth restriction.

Pregnant women with normal (n=65) or preeclamptic pregnancies with (n=42) or without (n=22) fetal growth restriction were included before cesarean delivery. sFlt-1 expression was quantified in maternal serum and umbilical cord blood (BRAHMS KRYPTOR) and by immunohistochemistry with semi-automated image analysis in decidual and placental tissue.

Decidual and placental sFlt-1 expression was trophoblast-dependent and selectively upregulated in preeclampsia without and with fetal growth restriction, respectively, and maternal serum sFlt-1 was elevated in both preeclampsia subtypes (P<0.001, all comparisons). sFlt-1 expression showed a positive correlation between decidua and placenta but did not correlate with maternal serum levels. Maternal serum sFlt-1 levels diverged: with high levels (>11 500 pg/mL) only in preeclamptic pregnancies (n=21) and low levels (<11 500 pg/mL) in all normal pregnancies (n=28) and 42% (n=15) of preeclamptic pregnancies.

sFlt-1 expression correlates across the maternal-fetal interface but is not directly reflected in maternal serum. The relationship to preeclampsia subtypes is complex.