Extracellular Matrix and Absent Decidua Dysregulate the Epithelial to Mesenchymal Transition in Extravillous Trophoblast in Placenta Accreta Spectrum

Abstract Our study purpose was to describe the extracellular matrix (ECM) surrounding the placental implantation site and the interaction between ECM and trophoblast to understand causal mechanisms of placenta accreta spectrum (PAS). Utero-placental tissue from PAS cases and normal myometrium was compared with non-PAS postpartum hysterectomy placental bed. HTR8/SVneo cells were used to investigate first trimester invasion. Evaluation was performed immunohistochemical staining (IHC) and Transwell invasion assays. Our outcome measures were histological scores of IHC and percent invasion for transwell assays. PAS specimens had absent decidua and placental villi in direct myometrial contact. EVT were encased within ECM containing Type IV collagen, fibronectin and Type III collagen rather than Type I Collagen. Positive staining was present for all wound remodeling factors tested in PAS EVT with differential ECM expression between PAS and non-PAS samples. Transwell assays showed Type III collagen promoting cell invasion whereas other ECM was inhibitory. Absence of mature Type I Collagen suggests that over previous cesarean scar, the area of trophoblast invasion behaves like an active wound. The invasion assays confirm that ECM differences result in altered trophoblast behavior. The extracellular matrix itself, as well as the absence of decidua impact the invasive behavior of placental trophoblast cells.