Identification of Infertility-Associated Topologically Important Genes Using Weighted Co-expression Network Analysis.

Jingni Wu,Xiaomeng Xia,Sandra Orsulic,Xiaoling Fang,Ye Hu

doi:10.3389/fgene.2021.580190

Abstract

Endometriosis has been associated with a high risk of infertility. However, the underlying molecular mechanism of infertility in endometriosis remains poorly understood. In our study, we aimed to discover topologically important genes related to infertility in endometriosis, based on the structure network mining. We used microarray data from the Gene Expression Omnibus (GEO) database to construct a weighted gene co-expression network for fertile and infertile women with endometriosis and to identify gene modules highly correlated with clinical features of infertility in endometriosis. Additionally, the protein–protein interaction network analysis was used to identify the potential 20 hub messenger RNAs (mRNAs) while the network topological analysis was used to identify nine candidate long non-coding RNAs (lncRNAs). Functional annotations of clinically significant modules and lncRNAs revealed that hub genes might be involved in infertility in endometriosis by regulating G protein-coupled receptor signaling (GPCR) activity. Gene Set Enrichment Analysis showed that the phospholipase C-activating GPCR signaling pathway is correlated with infertility in patients with endometriosis. Taken together, our analysis has identified 29 hub genes which might lead to infertility in endometriosis through the regulation of the GPCR network.

Highlights

Endometriosis, a gynecological disorder characterized by the growth of endometrial glands and stroma outside the uterus, is clinically highly associated with infertility
To identify all co-expressed genes, we chose β = 12 as the soft threshold to construct a scale-free weighted gene co-expression network (Figure 3A). long non-coding RNAs (lncRNAs) and messenger RNAs (mRNAs) with similar expression patterns were assigned to coexpression modules; 19 co-expression modules were identified and are shown in different colors (Figure 3B)
Endometriosis is associated with female infertility, but the molecular mechanisms underlying infertility are poorly understood

Summary

Introduction

Endometriosis, a gynecological disorder characterized by the growth of endometrial glands and stroma outside the uterus, is clinically highly associated with infertility. The mechanisms of infertility in endometriosis remain unclear. Increasing evidence has suggested that endometriosis patients have an abnormal endometrial environment, such as dysregulated hormone levels and activated inflammatory factors, which is unfavorable for embryo implantation and pregnancy progression (de Ziegler et al, 2010; Lessey and Kim, 2017). Some women with endometriosis can conceive without difficulty while others are infertile. Infertility in endometriosis appears to be a complex multifactorial clinical condition. Current medical treatments for endometriosis are not effective against infertility, and surgical treatment may induce the failure of ovarian function.

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Conclusion