Oral Concurrent Session 7 – Basic and Translational Science

Objective: Placenta accreta spectrum (PAS) represents abnormal placental adherence and uterine wall infiltration.While deep infiltration (FIGO grade 3) is mediated by cesarean scar dehiscence, the mechanism of adherence beyond the scar remains elusive.We hypothesize that the microenvironment in the area of scar is propagated along the utero-placental interface.Study Design: Fresh samples were obtained along the uteroplacental interface in hysterectomies for PAS; adjacent to scar (PAS-deep) and in areas of placental adherence distant from the scar (PAS-superficial).Placental bed punch biopsies were obtained from non-PAS hysterectomies with placenta previa (non-PAS controls).Proteomics 11k SomaScan v5.0 assay data was analysed for placenta enriched proteins.Differences were reported using t-test, p < 0.05 was considered significant.Results: Samples included 12 PAS cases with paired tissue from PAS-deep and PAS-superficial areas, and 9 non-PAS controls.There were significant changes in protein abundance between PAS-deep and non-PAS controls (Figure 1).PSG3, ADAM12, and MAGEA8 were differentially expressed in areas of PAS-deep compared to PAS-superficial areas (all p ≤ 0.035) (Figure 2).The findings suggest over-activation of placental implantation along the utero-placental interface in a gradient extending from the scar.There were significant differences in expression of PSG1, PSG9, PSG3, ISM2, ADAM12, and LUM in PAS-invasive compared to non-PAS samples.(all p ≤ 0.002) Conclusion: Proteomics analysis shows a gradient of proteins related to implantation from areas of deep penetration to superficial adherence, supporting a model in which PAS arises from abnormal implantation adjacent to cesarean scar dehiscence.Proteins involving angiogenesis, extracellular matrix remodeling, trophoblast invasion and immune modulation were discovered, potentially highlighting their role in pathogenesis of PAS.These finding suggest paracrine signaling may extend the uterine scar leading to a gradient of placental adherence.