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. Transcriptome sequencing of endometrial samples LH-timed to the WOI (LH+7 – LH+9) between women with and without sonographic features of adenomyosis

研究目的：本研究对比存在子宫腺肌病与无子宫腺肌病的女性在植入窗口（window of implantation，WOI）时期的子宫内膜转录组表达谱。
研究方法：本研究从具有超声提示腺肌病特征的女性（n=10）及对照组（n=10）中，获取了以黄体生成素（luteinizing hormone，LH）标定植入窗口时间的子宫内膜活检样本。提取的RNA样本经RNA测序（RNA-seq）后，使用用于月经周期分期的分子工具beREADY®（CCHT）完成子宫内膜容受性分类。后续结合精准子宫内膜分期的结果对RNA测序数据进行分析。
研究结果：20份子宫内膜样本中，2份被判定为早期容受期，13份为容受期，5份为晚期容受期。对全部20份样本的转录组数据进行比较后，腺肌病组共得到909个差异表达基因（differentially expressed genes，DEGs，p<0.05），但经校正p值后无统计学意义，仅富集到4条通路（邦费罗尼（Bonferroni）校正p值<0.05）。仅对分期为容受期的13份样本进行分析时，腺肌病组得到382个差异表达基因（p<0.05，校正p值后无统计学意义，仅具提示意义），最终富集到33条通路（邦费罗尼校正p值<0.05）。上述通路与子宫内膜生物学功能已存在关联，例如“干扰素（interferon，IFN）诱导基因的表达”及“对α干扰素的应答”。
研究结论：精准子宫内膜分期联合RNA测序分析发现，干扰素信号通路应答异常是腺肌病患者子宫容受性受损的最具潜力的候选机制。本研究对以LH标定植入窗口（LH+7至LH+9）的子宫内膜样本开展转录组测序，纳入存在与无超声提示腺肌病特征的女性。