Fig. 2: Figure summarises the findings of the changes seen in severe PAS cases, comparing these to previously reported findings in pre-eclampsia.

In a normal pregnancy, EVT gain invasive properties from CCT via EMT and divide into endovascular (transform spiral arteries into low resistance vessels) and interstitial EVTs (invade the decidua and superficial myometrium). In PAS, the decidua is absent or deficient, and the maternal myometrium is scarred and thinned. EVTs gain deep access to the myometrium in PAS, while pre-eclampsia is characterised by shallow EVT invasion. The figure shows findings seen in our study in severe PAS are often mirrored in pre-eclampsia²². In PAS, many transcription factors involved in normal trophoblast invasion are upregulated and these have previously been found to be downregulated in pre-eclampsia. Similarly, we found PAS regions expressed anti-apoptotic markers possibly resulting in increased cell-proliferation, while placentas in pre-eclampsia are pro-apoptotic. Immune changes seen at the maternal-foetal interface in PAS, such as increased PD-L1 and PD-L2, may allow trophoblast cells to escape the normal immune regulators of trophoblast invasion. Again, the mirror findings were previously reported in pre-eclampsia. Similarly, changes seen in the maternal serum in PAS, such as increased sTIE-2 and VEGF-A, the reverse findings were previously demonstrated in pre-eclampsia. vCTB villous cytotrophoblast. ST Syncytiotrophoblast. CCT cytotrophoblast column. EVT extravillous trophoblast. EMT epithelial to mesenchymal transition. ECM Extracellular Matrix.