Abstract:
The endometrium is of crucial importance for mammalian reproduction and undergoes dynamic reiterative tissue remodeling during the menstrual cycle. Knowledge on cellular and molecular underpinnings of the endometrium’s biological remodeling is poor, as well as on the processes that go awry in endometrium pathogenesis. Therefore, we embarked on the development of novel organoid research models for human healthy endometrium as well as a wide spectrum of endometrial diseases.

We established organoids from healthy endometrium which strongly reproduced the tissue’s epithelium phenotype. The organoids phenocopied the physiological responses to reproductive hormones thereby mimicking the menstrual cycle ‘in a dish’. Furthermore, the organoids showed long-term expansion capacity while remaining genomically, transcriptomically and functionally stable.

Long-term expandable organoids could also be established from a broad range of endometrium pathologies, ranging from endometriosis and endometrium hyperplasia to low and high grade endometrial cancer. The organoids recapitulated characteristics of the patients' disease and faithfully captured the clinical heterogeneity of the different pathologies. Moreover, endometrial disease organoids reproduced the original lesion when transplanted in vivo.

Taken together, we established new organoid models for endometrium and a wide spectrum of endometrial diseases, thereby providing powerful tools to decipher the mechanisms underlying biology and pathology of this key reproductive organ. The eventually generated organoid biobank will at the same time provide a screening platform to test (new) drugs, even in a patient-personalized manner.