Lower pregnancy rate in women with uterine adenomyosis is associated with impaired endometrial receptivity for embryo implantation. The underlying molecular causes are poorly understood due to past technological limitations of non-invasive methods to diagnose adenomyosis. We therefore applied systems biology approaches to identify candidate biological pathways/genes of altered endometrial receptivity in adenomyosis. We performed RNA sequencing (RNA-seq) analysis of the endometrium in the expected receptive state in women with (n = 10) and without (n = 10) ultrasound signs of adenomyosis. The identified differentially expressed genes were further integrated with data from the literature mining to understand their relevance in the context of endometrial molecular biology. We gathered reported transcripts and proteins associated with endometrial receptivity in adenomyosis, in related but better-studied endometriosis and in healthy uterus, and adopted their gene nomenclature according to the HGNC database. The comparison of RNA-seq data of only confirmed receptive samples (8 adenomyosis and 5 controls) identified 382 differentially expressed genes (p < 0.05) further mostly enriched in pathways associated with responses to interferon signalling and in pathway related to cell adhesion. By integration of gathered 382 (RNA-seq), 42 (adenomyosis), 173 (endometriosis) and 151 (healthy uterus) genes we identified enriched pathways extracellular matrix organisation, regulation of reproductive processes, VEGF response and signalling by interleukins, which we propose as additional candidate pathway for studying endometrial receptivity in adenomyosis. Our RNA-seq results are limited by insignificant gene expression difference after p-value correction (FDR > 0.05), which may be due to the small sample size. Based on the analysis of existing literature and own RNA-seq results, we conclude that endometrial receptivity in adenomyosis is altered at the level of immune cytokine signalling.
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