Transcriptomics of receptive endometrium in women with sonographic features of adenomyosis

Erika Prašnikar, Tanja Kunej, Mario Gorenjak, Uroš Potočnik, Borut Kovačič, Jure Knez
Reproductive biology and endocrinology : RB&E · 2022 · vol. 20(1) , pp. 2 · doi:10.1186/s12958-021-00871-5 · PMID:34980152 · W4205523950
article OA: gold CC0 ⤵ 5 in-corpus citations
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⚙ AI-generated summary by claude@2026-06, 2026-06-08 ⓘ

This study compared endometrial transcriptomes in women with and without adenomyosis during the window of implantation, identifying altered interferon signaling and extracellular matrix organization as potential mechanisms for impaired uterine receptivity.

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⚙ AI-generated deep summary by claude@2026-06, 2026-06-08 ⓘ

This prospective observational study compared endometrial transcriptome profiles during the LH-timed window of implantation between 10 women with sonographic features of adenomyosis and 10 controls, using RNA-seq on the Illumina NovaSeq 6000 plus molecular endometrial dating with beREADY® (CCHT). Across all 20 samples, the adenomyosis group showed 909 differentially expressed genes (nominal p<0.05, not significant after adjusted p), but enrichment analyses yielded only four significant pathways; when re-analyzed after excluding samples classified as early or late receptive to reduce menstrual phase effects, 382 DEGs and 33 enriched pathways emerged. Integrative enrichment combining adenomyosis-related DEGs with published endometrial receptivity gene sets highlighted altered interferon signaling (e.g., interferon-induced gene expression) and pathways involving extracellular matrix organization and tumor necrosis factor production as candidates for impaired receptivity. The paper relates to endometriosis and adenomyosis by focusing centrally on adenomyosis and explicitly integrating endometriosis gene sets into its pathway prioritization framework.

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Abstract

BACKGROUND: Women with uterine adenomyosis seeking assisted reproduction have been associated with compromised endometrial receptivity to embryo implantation. To understand the mechanisms involved in this process, we aimed to compare endometrial transcriptome profiles during the window of implantation (WOI) between women with and without adenomyosis. METHODS: We obtained endometrial biopsies LH-timed to the WOI from women with sonographic features of adenomyosis (n=10) and controls (n=10). Isolated RNA samples were subjected to RNA sequencing (RNA-seq) by the Illumina NovaSeq 6000 platform and endometrial receptivity classification with a molecular tool for menstrual cycle phase dating (beREADY®, CCHT). The program language R and Bioconductor packages were applied to analyse RNA-seq data in the setting of the result of accurate endometrial dating. To suggest robust candidate pathways, the identified differentially expressed genes (DEGs) associated with the adenomyosis group in the receptive phase were further integrated with 151, 173 and 42 extracted genes from published studies that were related to endometrial receptivity in healthy uterus, endometriosis and adenomyosis, respectively. Enrichment analyses were performed using Cytoscape ClueGO and CluePedia apps. RESULTS: Out of 20 endometrial samples, 2 were dated to the early receptive phase, 13 to the receptive phase and 5 to the late receptive phase. Comparison of the transcriptomics data from all 20 samples provided 909 DEGs (p<0.05; nonsignificant after adjusted p value) in the adenomyosis group but only 4 enriched pathways (Bonferroni p value < 0.05). The analysis of 13 samples only dated to the receptive phase provided suggestive 382 DEGs (p<0.05; nonsignificant after adjusted p value) in the adenomyosis group, leading to 33 enriched pathways (Bonferroni p value < 0.05). These included pathways were already associated with endometrial biology, such as "Expression of interferon (IFN)-induced genes" and "Response to IFN-alpha". Data integration revealed pathways indicating a unique effect of adenomyosis on endometrial molecular organization (e.g., "Expression of IFN-induced genes") and its interference with endometrial receptivity establishment (e.g., "Extracellular matrix organization" and "Tumour necrosis factor production"). CONCLUSIONS: Accurate endometrial dating and RNA-seq analysis resulted in the identification of altered response to IFN signalling as the most promising candidate of impaired uterine receptivity in adenomyosis.

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Condition tags

endometriosisadenomyosis

MeSH descriptors

Adenomyosis Adenomyosis Adenomyosis Adenomyosis Embryo Implantation Endometrium Transcriptome Adult Case-Control Studies Embryo Implantation Endometrium Endometrium Female Gene Expression Profiling Humans Pregnancy Slovenia Ultrasonography

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