利用子宫内膜类器官解析子宫肌瘤患者的子宫内膜功能障碍：一项初步研究。
Deciphering endometrial dysfunction in patients with uterine myoma using endometrial organoids: a pilot study.
机构信息
State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Cheeloo College of Medicine, Shandong University, China.; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, China.; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, China.; Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, China.
State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Cheeloo College of Medicine, Shandong University, China.; National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, China.; Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, China.
出版信息
Reprod Biomed Online. 2024 Nov;49(5):104355. doi: 10.1016/j.rbmo.2024.104355. Epub 2024 Jul 3.
RESEARCH QUESTION
What influence does an intramural myoma have on the endometrium, and how is this mediated?
DESIGN
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.
RESULTS
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.
CONCLUSIONS
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.
研究问题
壁内肌瘤对子宫内膜有何影响，其介导机制如何？
设计
从 13 名接受非腔室变形壁内肌瘤切除术（直径≤4cm；国际妇产科联合会 4 型）的患者和 13 名因良性宫颈疾病接受子宫切除术且临床基线相似的无肌瘤患者中收集子宫内膜。体外建立子宫内膜类器官，并通过雌激素和孕激素诱导其达到分泌期。对 3 名肌瘤患者和 3 名对照参与者未经处理和分泌期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）验证。
结果
数据显示，有肌瘤的未经处理的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进一步研究分泌期。有肌瘤的分泌期子宫内膜类器官中乙酰-α-微管蛋白、ODF2 和 TPPP 发生更大变化，可能提示纤毛减少，COL6A1 用作细胞外基质（ECM）建模增加的标志物。有肌瘤的未经处理和分泌期子宫内膜类器官均显示与 ECM 机械转导相关的基因和途径上调。有肌瘤的子宫内膜类器官中接受相关基因的表达模式受到干扰。
结论
本研究首次揭示壁内肌瘤在未经处理和分泌期子宫内膜类器官中产生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，表明壁内肌瘤损害子宫内膜蜕膜化和接受能力。
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