Tommy's National Centre for Miscarriage Research, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.
Tommy's National Centre for Miscarriage Research, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK.
Eur J Obstet Gynecol Reprod Biol. 2021 Jun;261:211-216. doi: 10.1016/j.ejogrb.2021.04.041. Epub 2021 Apr 30.
To characterise the endometrial transcriptomic profiles of women who suffered recurrent miscarriage and to set the foundation for the development of an endometrial receptivity test that could predict the fate of subsequent pregnancies.
This was a prospective multicentre cohort study performed at the Tommy's National Centre for Miscarriage Research in Birmingham, Saint Mary's Hospital in Manchester and Royal Devon & Exeter Hospital, United Kingdom. The study was conducted between December 2017 and December 2019. Endometrial biopsies were obtained during the window of implantation from 24 women aged 18-35 years, who were not pregnant and regularly menstruating, diagnosed with unexplained recurrent miscarriage by standard investigations as per the ESHRE guidelines. Exclusion criteria included risk factors such as smoking, obesity or hyperprolactinemia. The RNA transcripts abundances were quantified using Kallisto. R packages tximport and DESeq2 were used to summarize count estimates at the gene level and to analyse the differential gene expression.
Women who suffered four or more miscarriages had 19 differently expressed genes after adjustment for multiple comparisons. They were related to biological processes such as immunity (HLA-DMA, CCR8, ALOX5), energy production (ATP12A), hormone secretion (CGA), adhesion (CHAD, ADGRF2, AQP5, TBCD, CTNND1, NKD2) and cell proliferation (NCCRP1). Based on 421 differently expressed genes, women who achieved a subsequent live birth displayed an enrichment of processes related to the regulation of cell structure and proliferation, and a depletion of processes related to immunity, trans-membrane transport and coagulation.
Women in the extreme miscarriage cohort had a distinctive endometrial transcriptomic signature compared to women with low order miscarriages. There was a partial overlap with the transcriptome of asynchronous endometrium suggesting the endometrial factor to be a different entity in the context of recurrent miscarriage. Women who achieved a live birth in their subsequent pregnancy displayed an enrichment of genes related to the regulation of cell structure and proliferation, while women who suffered a subsequent miscarriage displayed an enrichment of genes related to immunity, trans-membrane transport and coagulation.
描绘反复性流产女性的子宫内膜转录组特征，并为开发预测后续妊娠结局的子宫内膜容受性检测奠定基础。
这是一项在英国伯明翰汤米国家流产研究中心、曼彻斯特圣玛丽医院和德文郡皇家埃克塞特大教堂医院进行的前瞻性多中心队列研究。研究于 2017 年 12 月至 2019 年 12 月进行。从 24 名年龄在 18-35 岁之间的未怀孕且月经规律的女性的着床窗口期获取子宫内膜活检，这些女性通过 ESHRE 指南规定的标准检查被诊断为不明原因的反复性流产。排除标准包括吸烟、肥胖或高泌乳素血症等危险因素。使用 Kallisto 定量 RNA 转录物丰度。使用 R 包 tximport 和 DESeq2 对基因水平的计数估计进行汇总，并分析差异基因表达。
在调整多重比较后，经历过四次或更多次流产的女性有 19 个差异表达的基因。它们与生物过程有关，如免疫（HLA-DMA、CCR8、ALOX5）、能量产生（ATP12A）、激素分泌（CGA）、黏附（CHAD、ADGRF2、AQP5、TBCD、CTNND1、NKD2）和细胞增殖（NCCRP1）。基于 421 个差异表达基因，实现后续活产的女性显示出与细胞结构和增殖调节相关过程的富集，以及与免疫、跨膜转运和凝血相关过程的消耗。
与低序流产的女性相比，极端流产组的女性具有独特的子宫内膜转录组特征。与异步子宫内膜的转录组有部分重叠，表明在反复性流产的背景下，子宫内膜因素是一种不同的实体。在后续妊娠中实现活产的女性显示出与细胞结构和增殖调节相关基因的富集，而经历后续流产的女性显示出与免疫、跨膜转运和凝血相关基因的富集。
