Yu Zhang , Minghui Lu , Yanli Han , Boyang Liu , Rusong Zhao , Peishu Liu , Han Zhao
{"title":"利用子宫内膜器官组织解密子宫肌瘤患者的子宫内膜功能障碍：一项试点研究","authors":"Yu Zhang , Minghui Lu , Yanli Han , Boyang Liu , Rusong Zhao , Peishu Liu , Han Zhao","doi":"10.1016/j.rbmo.2024.104355","DOIUrl":null,"url":null,"abstract":"<div><h3>Research question</h3><p>What influence does an intramural myoma have on the endometrium, and how is this mediated?</p></div><div><h3>Design</h3><p>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 <em>in vitro</em> 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.</p></div><div><h3>Results</h3><p>The data revealed abnormally increased hormone receptor (<em>PGR</em>) 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, <em>ODF2</em> and <em>TPPP</em>, demonstrating likely decreased cilia, and <em>COL6A1</em>, 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.</p></div><div><h3>Conclusions</h3><p>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.</p></div>","PeriodicalId":21134,"journal":{"name":"Reproductive biomedicine online","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1472648324005443/pdfft?md5=fdd5786b0971c58eca2f3690e3570225&pid=1-s2.0-S1472648324005443-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Deciphering endometrial dysfunction in patients with uterine myoma using endometrial organoids: a pilot study\",\"authors\":\"Yu Zhang , Minghui Lu , Yanli Han , Boyang Liu , Rusong Zhao , Peishu Liu , Han Zhao\",\"doi\":\"10.1016/j.rbmo.2024.104355\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Research question</h3><p>What influence does an intramural myoma have on the endometrium, and how is this mediated?</p></div><div><h3>Design</h3><p>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 <em>in vitro</em> 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.</p></div><div><h3>Results</h3><p>The data revealed abnormally increased hormone receptor (<em>PGR</em>) 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, <em>ODF2</em> and <em>TPPP</em>, demonstrating likely decreased cilia, and <em>COL6A1</em>, 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.</p></div><div><h3>Conclusions</h3><p>This study is the first to reveal that intramural myomas create an abnormal hormonal and mechanical environment in the untreated and secretory endometrial organoids. 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Deciphering endometrial dysfunction in patients with uterine myoma using endometrial organoids: a pilot study
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.
期刊介绍：
Reproductive BioMedicine Online covers the formation, growth and differentiation of the human embryo. It is intended to bring to public attention new research on biological and clinical research on human reproduction and the human embryo including relevant studies on animals. It is published by a group of scientists and clinicians working in these fields of study. Its audience comprises researchers, clinicians, practitioners, academics and patients.
Context:
The period of human embryonic growth covered is between the formation of the primordial germ cells in the fetus until mid-pregnancy. High quality research on lower animals is included if it helps to clarify the human situation. Studies progressing to birth and later are published if they have a direct bearing on events in the earlier stages of pregnancy.
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