Endometrial organoids derived from Mayer-Rokitansky-Ku? ster- Hauser syndrome patients provide insights into disease-causing pathways

The uterus is responsible for the nourishment and mechanical protection of the developing embryo and fetus and is an essential part in mammalian reproduction. Mayer???Rokitansky???Ku?? ster???Hauser (MRKH) syndrome is characterized by agenesis of the uterus and upper part of the vagina in females with normal ovarian function. Although heavily studied, the cause of the disease is still enigmatic. Current research in the field of MRKH mainly focuses on DNAsequencing efforts and, so far, has been unable to decipher the nature and heterogeneity of the disease, thereby holding back scientific and clinical progress. Here, we developed long-term expandable organoid cultures from endometrium found in uterine rudiment horns of MRKH patients. Phenotypically, they share great similarity with healthy control organoids and are surprisingly fully array of dysregulated genes that point to potentially disease-causing pathways altered during the development of the female reproductive tract. We consider the endometrial organoid cultures to be a powerful research tool that promise to enable an array of studies into the pathogenic origins of MRKH syndrome and possible treatment opportunities to improve patient quality of life.

Automated summary

MRKH syndrome is a condition characterized by the underdevelopment of the uterus and upper part of the vagina in females with normal ovarian function. The cause of the disease is still unknown and current research has been focused on DNA sequencing efforts. However, the development of long-term expandable organoid cultures from endometrium found in uterine rudiment horns of MRKH patients has provided insights into potential disease-causing pathways and treatment opportunities.