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作者

Zhang, Yu Lu, Minghui Han, Yanli Liu, Boyang Zhao, Rusong Liu, Peishu Zhao, Han

作者单位

¹State 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. ²National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, Shandong, China. ³Key Laboratory of Reproductive Endocrinology (Shandong University), Ministry of Education, Jinan, Shandong, China. ⁴Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong, China. ⁵The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China. ⁶Shandong Technology Innovation Center for Reproductive Health, Jinan, Shandong, China. ⁷Shandong Provincial Clinical Research Center for Reproductive Health, Jinan, Shandong, China. ⁸Shandong Key Laboratory of Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China. ⁹Research Unit of Gametogenesis and Health of ART-Offspring, Chinese Academy of Medical Sciences (No.2021RU001), Jinan, Shandong, China.

刊名

Reproductive BioMedicine Online (Elsevier Science)

年份

2024

卷号

Vol.49 No.5

ISSN

1472-6483

关键词

Endometrial organoids Hormone response Human endometrium Mechanotransduction Uterine myoma

摘要

Organoids formed from endometrium with an intramural myoma show pathological traits. • Intramural myomas impair the hormonal environment in basal endometrial organoids. • Intramural myomas disrupt the hormonal response in secretory endometrial organoids. • Intramural myomas alter the mechanical environment in endometrial organoids. 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 intra...更多

Organoids formed from endometrium with an intramural myoma show pathological traits. • Intramural myomas impair the hormonal environment in basal endometrial organoids. • Intramural myomas disrupt the hormonal response in secretory endometrial organoids. • Intramural myomas alter the mechanical environment in endometrial organoids. 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 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 were performed on endometrial organoids from another 10 myoma patients and 10 control patients for validation. The data revealed abnormally increased hormone receptor 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 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.收起

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