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Updated: Jun 13, 2025

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Establishing 3D Endometrial Organoids from the Mouse Uterus
Published on: January 6, 2023
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PCOS endometrium-derived epithelial organoids as a novel model to study endometrial dysfunction
L Luyckx1,2, M Wei3, U Saarela1
1Department of Obstetrics and Gynecology, Medical Research Centre, Research Unit of Clinical Medicine, Oulu University Hospital, University of Oulu, Oulu, Finland.
Human Reproduction (Oxford, England)
|June 11, 2025
Summary
Researchers established patient-derived endometrium epithelial organoids (EEOs) from women with PCOS, revealing increased inflammation and reduced receptivity. This novel model captures key endometrial abnormalities, offering insights into PCOS-related subfertility and pregnancy complications.
Area of Science:
- Reproductive biology and endocrinology.
- Organoid technology and in vitro modeling.
- Genetics and molecular mechanisms of PCOS.
Background:
- Endometrial dysfunction in Polycystic Ovary Syndrome (PCOS) contributes to subfertility and pregnancy complications.
- Previous research on the PCOS endometrial epithelial compartment is limited.
- No PCOS-derived endometrium epithelial organoids (EEOs) have been established previously.
Purpose of the Study:
- To establish PCOS-derived EEOs from patient samples.
- To investigate potential differences between PCOS EEOs and non-PCOS EEOs.
- To utilize EEOs as a model for studying endometrial dysfunction in PCOS.
Main Methods:
- EEOs were established from endometrial biopsies of women with PCOS (lean and overweight/obese) and BMI-matched controls.
- Organoids were cultured with steroid hormones and Wnt signaling inhibitors to simulate menstrual cycle phases, with/without androgen exposure.
- Bulk RNA-sequencing, RT-qPCR, and morphological assessments (H&E, immunostaining) were used to analyze gene expression and morphology.
Main Results:
- PCOS EEOs exhibited increased inflammation-related gene expression (OSMR, ICAM1) and reduced diameter compared to controls.
- Overweight/obese PCOS EEOs showed aberrant steroid hormone response, with reduced expression of receptivity genes (PAEP, LIF).
- Androgen exposure (DHT) did not significantly alter EEO transcriptome due to minimal androgen receptor expression.
Conclusions:
- Successfully established PCOS EEOs that recapitulate endometrial abnormalities, including inflammation and altered gene expression.
- This novel organoid model provides a valuable tool for understanding PCOS-related endometrial dysfunction and its impact on fertility.
- Findings suggest potential links between altered endometrial receptivity, inflammation, and increased pregnancy complications in PCOS.

