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

Abstract

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.

Keywords:

• Infertility
• endometriosis
• endometrium

Acknowledgements

The authors would like to thank the GEO training course of Helix-Life as well as Biotrainee for the training of bioinformatics analysis, and Dr. Jianming Zeng (CEO of Biotrainee) and Dr. Guozi (Chongqing Medical University) for generously sharing their experience and codes.

Author contributions

L.J. and X.L.F. conceived and designed the study. L.J., C.H., W.X., and T.T.Z. acquired and analyzed data. L.J., Z.M.W., T.J.L., Y.Q.W., Z.Y.L. helped interpreted data and prepared figures and tables. L.J. and X.L.F drafted the manuscript. L.J, W.X., T.T.Z., and Z.Y.L. revised the manuscript. All authors reviewed the manuscript. L.J and X.L.F gave the final approval of the version to be published.

Disclosure statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. No potential conflict of interest was reported by the author(s).

Data availability statement

The datasets GSE120103, GSE92324, GSE111974 for this study can be found in the NCBI GEO database (https://www.ncbi.nlm.nih.gov/geo/).

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [81671437, 81801425, 81771558]. The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript.