PRG2 and AQPEP are misexpressed in fetal membranes in placenta previa and percreta

Abstract

The obstetrical conditions placenta accreta spectrum (PAS) and placenta previa are a significant source of pregnancy-associated morbidity and mortality, yet the specific molecular and cellular underpinnings of these conditions are not known. In this study, we identified misregulated gene expression patterns in tissues from placenta previa and percreta (the most extreme form of PAS) compared with control cases. By comparing this gene set with existing placental single-cell and bulk RNA-Seq datasets, we show that the upregulated genes predominantly mark extravillous trophoblasts. We performed immunofluorescence on several candidate molecules and found that PRG2 and AQPEP protein levels are upregulated in both the fetal membranes and the placental disk in both conditions. While this increased AQPEP expression remains restricted to trophoblasts, PRG2 is mislocalized and is found throughout the fetal membranes. Using a larger patient cohort with a diverse set of gestationally aged-matched controls, we validated PRG2 as a marker for both previa and PAS and AQPEP as a marker for only previa in the fetal membranes membranes. Our findings suggest that the extraembryonic tissues surrounding the conceptus, including both the fetal membranes membranes and the placental disk, harbor a signature of previa and PAS that reflects increased trophoblast invasiveness.

Structural insights into the covalent regulation of PAPP-A activity by proMBP and STC2

“…With the establishment of the tissue model and single-cell RNA profiles 56,57 , more precise roles for PAPP-A activity will be discovered. ProMBP is abnormal in large-for-gestationalage (LGA) and shows mislocation in fetal membranes 58,59 . STC2 is regarded to be highly related to human height, as some STC2 variants containing the height-increasing alleles display compromised proteolytic inhibition of PAPP-A, leading to increased cleavage of IGFBP4 60,61 .…”