Epigenetic and transcriptomic characterization of maternal-fetal interface in patients with recurrent miscarriage via an integrated multi-omics approach.

Recurrent miscarriage (RM) occurs in 2.5 % of women aiming at childbirth, with unknown etiology in half of the cases. To identify the molecular features, an integrative study combining bioinformatics and multi-omics from GEO database was performed in these patients. Two datasets (GSE43256 and GSE73025) were integrated to indicate 1657 differentially expressed genes (DE-genes) in villus of females with RM. DE-genes in villus of females with RM mainly focused on cell growth and development. On the other hand, 230 DE-genes in decidua of RM patients were retrieved from GSE113790, and the DE-genes were involved in diverse functions, including transport of nutrients, immune response, extracellular matrix remodeling, and angiogenesis. Additionally, the results of immunologic signatures indicated that immune regulation played roles in both decidua and villus of RM. Interestingly, C1q and TNF related 7 (C1QTNF7), acquired from the intersection of decidua and villus datasets, is crucial in maintaining immune homeostasis, so is its upstream miRNA (miR-149-3p). The enhanced expression of C1QTNF7 in macrophages might inhibit the proliferation and migration of trophoblasts, and further result in pregnancy loss. The present study suggests C1QTNF7 might be a new target for the diagnosis and treatment of RM, but more basic researches are further required to illustrate its mechanism in RM.