Journal Article

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

Hannibal, Roberta L., Badillo Rivera, Keyla M., Urban, Alexander E., Zhang, Elisa T., Song, Janet H.T., McGowan, Kelly, Lyell, Deirdre J., Folkins, Ann K., Baker, Julie C., Meinhardt, Gudrun, Zhu, Xiaowei, Knöfler, Martin, Pollheimer, Jürgen

2021

Overview

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. Our findings suggest that the extraembryonic tissues surrounding the conceptus, including both the fetal membranes and the placental disk, harbor a signature of previa and PAS that is characteristic of EVTs and that may reflect increased trophoblast invasiveness. Summary sentence 3SEQ and immunofluorescence reveal that extravillous trophoblast factors, most notably PRG2 and AQPEP, define the diseases placenta previa and placenta accreta spectrum in both the chorioamniotic membranes and the placental disk.

• Publisher: Society for the Study of Reproduction,Oxford University Press
• Subject: AQPEP / Comparative analysis / Eosinophil Major Basic Protein - genetics / Eosinophil Major Basic Protein - metabolism / Extraembryonic Membranes - metabolism / Female / fetal membranes / Fetuses / Gene expression / Gene Expression Regulation / Genes / Health aspects / Humans / Immunofluorescence / Invasiveness / Metalloproteases - genetics / Metalloproteases - metabolism / Morbidity / Mortality / Placenta / Placenta Accreta - metabolism / placenta accreta spectrum / placenta previa / Placenta Previa - metabolism / Pregnancy / Pregnancy complications / PRG2 / Proteoglycans - genetics / Proteoglycans - metabolism / RESEARCH ARTICLE / RNA / RNA sequencing / Trophoblasts