Patterns of Gene Expression in Chorionic Villous Tissue Based on Patterns of Placental Pathology

Background: We sought to investigate gene expression in placentas impacted by major patterns of injury: acute inflammation (AI), chronic inflammation (CI), and maternal vascular malperfusion (MVM). Methods: We utilized placental tissue prospectively collected between 2017 and 2020. Chorionic villous biopsies were collected following delivery and samples were also submitted for histologic examination. Placentas with ≥2 types of placental injury after histology examination were excluded. Linear models, adjusted for covariates, were used to compare each pathology group to histologically normal control placentas. Transcripts with fold-change of >2 or <0.5 served as input for higher-order bioinformatic analyses, focused on identifying transcription control pathways and the cellular populations involved. Results: One hundred and sixty-four placentas were included: 60 AI, 25 CI, 39 MVM, and 40 controls. In bioinformatic analyses each pathology group displayed a unique signature, with distinct transcription binding factor activity involved including pathways involved in cell signaling, cell proliferation, and cell differentiation. Conclusion: We show unique patterns of transcriptional control for each pathology-defined type of placental injury. MVM, CI, and AI represent not only unique histologic patterns, but also express unique molecular signatures.