Identification of key functional pathways: arginine biosynthesis and IL-17 signalling in placental decidua of unexplained recurrent pregnancy loss through RNA sequencing—a case series

Abstract

Three or more consecutive pregnancy losses before the 20th week of gestation constitute recurrent pregnancy loss (RPL), and about half of these cases are still unsolved despite routine screening tests. The purpose of the current study was to identify the RPL-related placental decidual differential gene expression and to gain new knowledge about the biological mechanisms underlying RPL. In the current work, we used RNA sequencing (RNA-seq) technology to identify the differentially expressed genes (DEGs) in placental decidua from patients of unexplained recurrent pregnancy loss (RPL). To conduct RNA-seq, two healthy unwanted medically terminated pregnancies (MTPs) and four RPL patients were enlisted. A total number of 96 significant differentially expressed genes (DEGs) were obtained which includes 73 up- and 23 downregulated genes between the RPL and MTP groups. Histocompatibility genes were significantly upregulated in the RPL. Interleukin 6 (IL-6), matrix metalloproteinase-10 (MMP10), and protein phosphatase 1 regulatory inhibitor subunit 11 (PPP1R11) genes which were significantly upregulated in RPL were further validated in an extended sample size. The validation results were consistent with the sequencing results. To find potential biological pathways connected to RPL, the Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were carried out. The study indicates that arginine biosynthesis is significantly downregulated, while IL-17 signalling pathway is significantly upregulated in RPL. In conclusion, the findings of the present study indicate involvement of arginine biosynthesis, immune regulatory pathways, and histocompatibility genes in the pathogenesis of recurrent pregnancy loss (RPL). However, to validate these observations, further investigations with a larger sample size are warranted.