Transcriptomics of receptive endometrium in women with sonographic features of adenomyosis

Prašnikar, Erika (author), Kunej, Tanja (author), Gorenjak, Mario (author), Potočnik, Uroš (author), Kovačič, Borut (author), Knez, Jure (author)

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 profles 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 classifcation 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 identifed diferentially 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; nonsignifcant 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; nonsignifcant 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 efect 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 identifcation of altered response to IFN signalling as the most promising candidate of impaired uterine receptivity in adenomyosis.

• Language: English
• Keywords: adenomyosis, assisted reproductive techniques (ART), data integration, endometrial receptivity, enrichment pathway analysis, omics approaches, RNA-seq, systems biology, transcriptomics, window of implantation
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: BF - Biotechnical Faculty
• Publication status: Published
• Publication version: Version of Record
• Year: 2022
• Number of pages: 16 str.
• Numbering: Vol. 20, art. 2
• PID: 20.500.12556/RUL-134676
• UDC: 616:575
• ISSN on article: 1477-7827
• DOI: 10.1186/s12958-021-00871-5
• COBISS.SI-ID: 91852035
• Publication date in RUL: 25.01.2022

Record is a part of a journal

• Title: Reproductive biology and endocrinology
• Shortened title: Reprod Biol Endocrinol
• Publisher: BioMed Central
• ISSN: 1477-7827
• COBISS.SI-ID: 2610708

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.
• Licensing start date: 03.01.2022

Secondary language

• Language: Slovenian
• Keywords: medicina, adenomioza, genetika

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: P3-0327
• Name: Reprodukcija človeka - laboratorijski in eksperimentalni vidiki

• Funder: ARRS - Slovenian Research Agency
• Project number: P4-0220
• Name: Primerjalna genomika in genomska biodiverziteta