Establishment and characterization of endometrial organoids derived from MRKHS patients

Background The Mayer-Rokitansky-Küster-Hauser-syndrome (MRKHS) is characterized by aplasia of the uterus and vagina. The endometrium of the uterine rudiments shows a highly reduced proliferative capacity. Additionally, decidualization is impaired in vitro for endometrial stroma cells derived from MRKHS patients. However, it remains unclear if this deficiency also applies to the epithelial cells of the endometrium.

Materials and methods We successfully established three-dimensional organoid models from tissue derived from MRKHS patients and healthy controls, which represent the endometrial glandular epithelium of the patient. Endometrium was acquired from five patients with MRKHS (16-20 years, MRKH type 1) and several healthy controls. Growth patterns were compared between MRKH organoids and controls. After hormonal stimulation with estrogen and progesterone or estrogen alone, organoid response was measured by means of expression changes of several marker genes (qPCR).

Results The MRKH organoids exhibited a regular growth pattern and were long-term expendable. No phenotypical differences were observed compared to control organoids and hormonal stimulation led to similar morphological changes. Upon treatment with estrogen or progesterone, MRKH organoids showed distinct changes in the expression of marker genes such as PAEP or SOX9. This result indicates normal hormone receptor functioning.

Conclusion We successfully established endometrial organoids from patients with MRKHS. The endometrial epithelial cells of MRKHS patients exhibited regular proliferation in our organoid model. Additionally, there was no indication for impaired decidualization, although past in vitro studies had indicated the opposite for endometrial stroma cells. In future, we will perform RNA-seq expression analysis for a more in-depth understanding.

Publication History

Article published online:
07 October 2020