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Significance The syndrome of cytotrophoblast invasion beyond the normal boundary (in the superficial myometrium) is collectively termed placenta accreta spectrum. The incidence of this condition is rising. However, little is known about the underlying molecular changes. Global transcriptomic profiling of cytotrophoblasts isolated from these cases, as compared to gestational age-matched controls, revealed numerous changes in gene expression involving diverse pathways, including cell signaling, migration, and immune functions.DOCK4 was the most highly up-regulated mRNA in the cases. Mutations in this gene are mechanistically linked to cancer progression. Overexpression of DOCK4 in primary cytotrophoblasts increased their invasiveness. This study provides molecular insights into the pathways driving placenta accreta spectrum and suggests numerous future directions.

Up-regulated cytotrophoblast DOCK4 contributes to over-invasion in placenta accreta spectrum