Transcriptomics of receptive endometrium in women with sonographic features of adenomyosis

Purpose: We compared endometrial transcriptome profiles during the window of implantation (WOI) between women with and without uterine adenomyosis. Methods: We obtained endometrial biopsies luteinizing hormone (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) and endometrial receptivity classification with a molecular tool for menstrual cycle phase dating (beREADY®, CCHT). RNA-seq data were analysed in the setting of the result of accurate endometrial dating. 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”. Conclusion: 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. Overall design: Transcriptome sequencing of endometrial samples LH-timed to the WOI (LH+7 – LH+9) between women with and without sonographic features of adenomyosis