使用子宫内膜类器官解读子宫肌瘤患者的子宫内膜功能障碍:一项试点研究。
Deciphering endometrial dysfunction in patients with uterine myoma using endometrial organoids: a pilot study.
发表日期:2024 Jul 03
作者:
Yu Zhang, Minghui Lu, Yanli Han, Boyang Liu, Rusong Zhao, Peishu Liu, Han Zhao
来源:
REPRODUCTIVE BIOMEDICINE ONLINE
摘要:
肌壁间肌瘤对子宫内膜有什么影响?这种影响是如何介导的?子宫内膜采集自 13 名非腔室扭曲性壁内肌瘤(直径 ≤ 4 cm;国际妇产科联合会 4 型)患者和 13 名非腔扭曲性壁内肌瘤患者。因良性宫颈疾病而接受子宫切除术的肌瘤具有相似的临床基线。在体外建立子宫内膜类器官,并通过雌激素和孕激素诱导达到分泌期。对三名肌瘤患者和三名对照参与者未经治疗和分泌阶段的子宫内膜类器官进行转录组测序。对另外 10 名肌瘤患者和 10 名对照患者的子宫内膜类器官进行免疫荧光和实时定量 PCR (RT-qPCR) 进行验证。数据显示,未经治疗的肌瘤子宫内膜类器官中激素受体 (PGR) 水平异常升高,导致潜在的腺体和血管发育异常。对雌激素和孕激素的异常反应促使人们进一步研究分泌阶段。具有肌瘤的分泌性子宫内膜类器官在乙酰-α-微管蛋白、ODF2 和 TPPP 方面表现出更大的变化,表明纤毛和 COL6A1 可能减少,COL6A1 用作细胞外基质 (ECM) 建模增加的标记。未经治疗的子宫内膜类器官和患有肌瘤的分泌性子宫内膜类器官均表现出与 ECM 机械转导相关的基因和途径的上调。子宫内膜类器官中接受性相关基因的表达模式受到干扰。这项研究首次揭示了壁内肌瘤在未经治疗的分泌性子宫内膜类器官中产生了异常的激素和机械环境。壁内肌瘤对与子宫内膜腺体、血管、纤毛和 ECM 相关的基因表达产生负面影响,表明壁内肌瘤会损害子宫内膜蜕膜化和容受性。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。
What influence does an intramural myoma have on the endometrium, and how is this mediated?Endometrium was collected from 13 patients with non-cavity-distorting intramural myomas (diameter ≤4 cm; International Federation of Gynecology and Obstetrics type 4) and 13 patients without myomas undergoing hysterectomy for benign cervical diseases with a similar clinical baseline. Endometrial organoids were established in vitro and induced to reach the secretory phase by oestrogen and progesterone. Transcriptome sequencing was conducted on endometrial organoids in both untreated and secretory stages from three individuals with myomas and three control participants. Immunofluorescence and real-time quantitative PCR (RT-qPCR) were performed on endometrial organoids from another 10 myoma patients and 10 control patients for validation.The data revealed abnormally increased hormone receptor (PGR) levels in the untreated endometrial organoids with myomas, resulting in potentially abnormal glandular and vascular development. The aberrant responses to oestrogen and progestogen prompted further investigation into the secretory phase. The secretory endometrial organoids with myomas exhibited greater changes in acetyl-α-tubulin, ODF2 and TPPP, demonstrating likely decreased cilia, and COL6A1, used as a marker for increased extracellular matrix (ECM) modelling. Both untreated and secretory endometrial organoids with myoma showed an up-regulation of genes and pathways related to ECM mechanotransduction. The expression pattern of receptivity-related genes was disturbed in endometrial organoids with myoma.This study is the first to reveal that intramural myomas create an abnormal hormonal and mechanical environment in the untreated and secretory endometrial organoids. The intramural myomas negatively impacted gene expression relating to endometrial glands, blood vessels, cilia and ECM, indicating that intramural myomas impair endometrial decidualization and receptivity.Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.