Key results
Subcutaneous administration and placenta-targeted delivery of CBX resulted in the hallmark of PE-like features including hypertension, proteinuria, renal damages, elevated circulatory sFlt1 level and increased sFlt1/ PlGF in pregnant rats. These animals displayed reduced trophoblast invasion in uterus, impaired spiral artery remodeling and reduced placental blood flow. In vitro study showed that 11β-HSD2 dysfunction inhibited migration and invasion of the extravillous trophoblasts and promoted sFlt1 release in syncytiotrophoblasts. Mechanically, sFlt1 release induced by 11β-HSD2 dysfunction is mediated by enhancement of a disintegrin and metalloprotease (ADAM)17 transcription in placenta.