Dysregulated infertility-related genes in women with endometriosis

Abstract

A number of mechanisms may be responsible for endometriosis-related infertility, such as inflammatory microenvironment, altered immune response, reduced/absent adhesion molecules and oxidative stress. Many genes play important roles in these processes and their expression levels may be altered in women with endometriosis. A prospective case-control study was conducted to assess expression of dysregulated genes in the eutopic endometrium of women with endometriosis compared to that of women without endometriosis. Eutopic endometrial biopsies from 29 women (N=16 with endometriosis; N=13 without endometriosis) were obtained by Pipelle curette between 1 January 2015 and 31 December 2015 in Akanksha IVF centre. Paralleled gene expression profiling using high density oligonucleotide microarrays was applied to investigate dysregulated genes in eutopic endometrium of women with endometriosis compared to women without endometriosis. Data analysis was conducted by GeneSpring version 4.0.4. T-test using P value >0.05 and a fold-change expression >1.5 was applied to assess statistical significance. Selected dysregulated genes were randomly chosen and validated by RT-PCR. This study has shown that in the eutopic endometrium from women with endometriosis infertility-related genes were significantly dysregulated. Particularly, genes involved in inflammation, immune response and oxidative stress were upregulated whereas genes involved in the expression of adhesion molecules were downregulated. Dysregulation of genes involved in infertility likely contributes to decreased pregnancy rates in women with endometriosis. Increased inflammation in the eutopic endometrium may contribute to increased cytokine production and altered immune environment leading to oxidative stress thereby impairing embryo implantation. Moreover, downregulation of adhesion molecules in the eutopic endometrium may affect the endometrial receptivity in women with endometriosis. An improved understanding of the underlying molecular infertility mechanisms may aid in identifying candidate genes for managing endometriosis-associated infertility.Tabled 1Table 1: Significantly dysregulated genes in eutopic endometrium of women with endometriosis (n=16)Gene SymbolGene nameFunctionFold ChangeCOL16A1Collagen, type XVI, alpha 1Adhesion-1.5ITGA6Integrin, alpha 6Adhesion-1.6GZMBGranzyme BInflammation3.05CXCL14Chemokine (C-X-C-motif) ligand 14Inflammation10.7ERO1LERO1-likeoxidative stress1.65HIST1H2ACHistone cluster 1, H2acoxidative stress2.29MAFFv-Mafmusculoaponeuroticfibrosarcoma oncogene homolog Foxidative stress2.26MAP3K5mitogen-activated protein kinase kinase kinase 5oxidative stress3.15CD68CD68 moleculeImmune response1.53CD58CD58 moleculeImmune response1.69TLR4Toll-like receptor 4Immune response1.75 Open table in a new tab