Down-regulation of HLA-DRs and HLA-DPs reflects the deficiency of antigen-presenting cells in endometrium from infertile women with and without ovarian endometriosis

This study aimed to explore common molecular changes in the infertile endometrium from women with and without endometriosis (EM). By analyzing the dataset GSE120103 from Gene Expression Omnibus, a total of 3252 shared differentially expressed genes were identified between ovarian EM in infertile vs. fertile endometrium and EM-free infertile vs. fertile endometrium. In addition, the gene annotation and pathway analysis of the shared differentially expressed genes with the same expression trend indicated that the pathway ‘MHC class II antigen presentation’ and five candidate genes: HLA-DRA, HLA-DRB1, HLA-DRB3, HLA-DPA1, HLA-DPB1 were both down-regulated in infertile endometrium with or without EM. Logistic regression showed that HLA-DRA might be an independent predictor of the infertile status of the endometrium. Single sample gene set enrichment analysis (ssGSEA) showed that some classic antigen-presenting cells: macrophages type 1, macrophages type 2, and mature dendritic cells were significantly down-regulated in infertile endometrium with or without EM, whose enrichment correlated positively with the expression of candidate HLA molecules. Hence, the down-regulation of HLA-DRs and HLA-DPs reflecting the deficiency of antigen-presenting cells in endometrium might serve as a common biomarker for diagnosing endometrium-associated infertility in women with and without endometriosis.

本研究旨在探究伴与不伴子宫内膜异位症（endometriosis, EM）女性不孕子宫内膜的共同分子改变。本研究通过分析基因表达综合数据库（Gene Expression Omnibus）中的GSE120103数据集，分别在不孕vs可育子宫内膜的卵巢型EM组与无EM不孕vs可育子宫内膜组中，共鉴定出3252个共有差异表达基因。此外，对表达趋势一致的共有差异表达基因进行基因注释与通路富集分析后发现，"主要组织相容性复合体II类抗原呈递"通路及HLA-DRA、HLA-DRB1、HLA-DRB3、HLA-DPA1、HLA-DPB1这5个候选基因，在伴或不伴EM的不孕子宫内膜中均呈下调表达。Logistic回归分析显示，HLA-DRA或可作为子宫内膜不孕状态的独立预测因子。单样本基因集富集分析（Single Sample Gene Set Enrichment Analysis, ssGSEA）结果显示，伴或不伴EM的不孕子宫内膜中，部分经典抗原呈递细胞——M1型巨噬细胞、M2型巨噬细胞及成熟树突状细胞均显著下调，其富集水平与候选HLA分子的表达呈正相关。综上，HLA-DR与HLA-DP家族的下调表达反映了子宫内膜中抗原呈递细胞的功能缺陷，其可作为伴与不伴EM女性子宫内膜相关性不孕的通用诊断生物标志物。