Scaffold-Free Endometrial Organoids Respond to Excess Androgens Associated With Polycystic Ovarian Syndrome
| Autor: | Margrit Urbanek, Teresa K. Woodruff, J. Julie Kim, Joanna E. Burdette, Zhenxiao Lu, Teerawat Wiwatpanit, Alina R Murphy |
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| Rok vydání: | 2019 |
| Předmět: |
Adult
0301 basic medicine medicine.medical_specialty Stromal cell medicine.drug_class Endocrinology Diabetes and Metabolism Clinical Biochemistry Endometrium Biochemistry 03 medical and health sciences 0302 clinical medicine Endocrinology Internal medicine Follicular phase medicine Organoid Humans Prospective Studies Clinical Research Articles Cell Proliferation 030219 obstetrics & reproductive medicine business.industry Endometrial cancer Biochemistry (medical) Middle Aged Prognosis Androgen medicine.disease Polycystic ovary Endometrial Neoplasms Organoids 030104 developmental biology medicine.anatomical_structure Estrogen Case-Control Studies Androgens Cancer research Female Stromal Cells Hyperandrogenism business Follow-Up Studies Polycystic Ovary Syndrome |
| Zdroj: | J Clin Endocrinol Metab |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/clinem/dgz100 |
| Popis: | ContextPolycystic ovary syndrome (PCOS) is a prevalent disorder in reproductive aged women associated with a number of endocrine and metabolic complications, including increased risk of endometrial cancer.ObjectiveTo study the effect of the characteristic increased androgen levels in PCOS on the endometrium, a novel scaffold-free multicellular endometrial organoid was established.DesignHuman endometrial organoids were constructed using primary endometrial epithelial and stromal cells from endometrial tissues. Organoids were treated for 14 days with physiologic levels of estradiol and testosterone to mimic a normal follicular phase or PCOS hormone profiles. Organoids were harvested for immunostaining and ribonucleic acid sequencing.SettingAcademic institution.PatientsEndometrial tissues from 10 premenopausal women undergoing hysterectomy for benign pathologies were obtained following written consent.Main Outcome MeasuresOrganoid architecture, cell specific markers, functional markers, proliferation, and gene expression were measured.ResultsA method to generate scaffold-free endometrial organoids containing epithelial and stromal cells was established. These organoids exhibited distinct organization with epithelial cells lining the outer surface and stromal cells in the center of the organoids. Epithelial cells were polarized, organoids expressed cell type specific and functional markers, as well as androgen, estrogen, and progesterone receptors. Treatment with PCOS hormones increased cell proliferation and dysregulated genes in endometrial organoids.ConclusionsA new multicellular, scaffold-free endometrial organoid system was established that resembled physiology of the native endometrium. Excess androgens in PCOS promoted cell proliferation in endometrial organoids, revealing new mechanisms of PCOS-associated with risk of endometrial neoplasia. |
| Databáze: | OpenAIRE |
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