Integrated Transcriptomic Analysis of the miRNA–mRNA Interaction Network in Thin Endometrium

Abstract

Although the thin endometrium (TE) has been widely recognized as a critical factor in implantation failure, the contribution of miRNA–mRNA regulatory network to the development of disease etiology remains to be further elucidated. This study performed an integrative analysis of the miRNA–mRNA expression profiles in the thin and adjacent normal endometrium of eight patients with intrauterine adhesion to construct the transcriptomic regulatory networks. A total of 1,093 differentially expressed genes (DEGs) and 72 differentially expressed miRNAs (DEMs) were identified in the thin adhesive endometrium of the TE group compared with the control adjacent normal endometrial cells. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that the DEGs and the target genes of DEM were significantly enriched in angiogenesis, cell growth regulation, and Wnt signaling pathway. Multiple hub genes (CAV1, MET, MAL2, has-mir-138, ARHGAP6, CLIC4, RRAS, AGFG1, has-mir-200, and has-mir-429) were identified by constructing the miRNA–mRNA regulatory networks. Furthermore, a miRNA–mRNA pathway function analysis was conducted, and the hub genes were enriched in the FoxO signaling pathway, cell growth regulation, inflammatory response regulation, and regulation of autophagy pathways. Our study is the first to perform integrated mRNA-seq and miRNA-seq analyses in the thin adhesive endometrium and the control adjacent normal endometrial cells. This study provides new insights into the molecular mechanisms underlying the formation of thin endometrium.

The Effect of Endometrial Thickness on Pregnancy, Maternal, and Perinatal Outcomes of Women in Fresh Cycles After IVF/ICSI: A Systematic Review and Meta-Analysis

“…We found that LBR, CPR, and IR were lower in patients with thin endometrium, which were consistence with previous studies (4,22,38). The underlying reason might not only be related to high oxygen levels in basal layer of endometrium, but also relevant to abnormal transcriptional changes in thin endometrium (39)(40)(41). For instance, a recent study revealed that differentially expressed genes and microRNAs, which were enriched in angiogenesis, cell growth regulation, and Wnt signaling pathway, were detected in the mid-secretary phase of thin endometrium compared to adjacent normal endometrial cells (41).…”

“…The underlying reason might not only be related to high oxygen levels in basal layer of endometrium, but also relevant to abnormal transcriptional changes in thin endometrium (39)(40)(41). For instance, a recent study revealed that differentially expressed genes and microRNAs, which were enriched in angiogenesis, cell growth regulation, and Wnt signaling pathway, were detected in the mid-secretary phase of thin endometrium compared to adjacent normal endometrial cells (41). Moreover, our results showed that though a thin endometrium had no effect on MR, but had higher chance of early miscarriage.…”

Molecular Characteristics of Choledochal Cysts in Children: Transcriptome Sequencing

“…We found that the genes were enriched in Wnt signaling pathway. The key signaling pathways are closely related to the basic developmental processes and the control of asymmetric cell division ( Zong et al, 2021 ). A previous study found that the Wnt pathway was activated in congenital CCs, but the activation level was lower than that in cholangiocarcinoma ( Chen et al, 2016 ).…”

Deciphering the endometrial niche of human thin endometrium at single-cell resolution

“…S4 A and B ). This may contribute to the impairment of angiogenesis and new blood vessel sprouting and ultimately result in insufficient vascularization, which has been reported as a key cause for thin endometrium ( 16 , 17 ). Expression of VCAN and MGP was significantly up-regulated in the stroma of thin endometrium ( SI Appendix , Fig.…”