Characterization of placental and decidual cell development in early pregnancy loss by single-cell RNA sequencing

Background: Early pregnancy loss (EPL) presents as sporadic or recurrent miscarriage during the first trimester. In addition to chromosomal defects, EPL may result from impairment of the placental-decidual interface at early gestational age due to gene-environmental interactions. Methods: To better understand the pathogenesis associated with this impairment, cell development in chorionic villi and decidua of different forms of EPL (sporadic or recurrent) was investigated with single-cell RNA sequencing and compared to that of normal first-trimester tissue. Results: Unique gene expression signatures were obtained for the different forms of EPL and for normal tissue and the composition of placental and decidual cell clusters in each form was established. In particular, the involvement of macrophages in the EPL phenotypes was identified revealing an immunoactive state. Conclusion: Differential gene expression and unique marker genes among cell clusters from chorionic villi and decidua of miscarried and normal pregnancies, may lead to identification of biomarker for EPL.