Decoded the cellular and molecular mechanisms of Asherman’s syndrome, a rare disease that leaves women without menstruation

An article published by the full professor of the Department of Paediatrics, Obstetrics and Gynaecology of the University of Valencia (UV) Carlos Simón and his research team (UV, INCLIVA and Carlos Simón Foundation) in the journal Nature Communications , describes for the first time the cellular alterations responsible for Asherman’s Syndrome at the single cell level. It also identifies gene expression profiles that create a dysfunctional environment, leading to scar tissue formation, inflammation, and vascular alterations. Asherman’s Syndrome is a rare disease characterised by intrauterine scars that cause menstrual disorders and infertility.

Patients diagnosed with moderate or severe Asherman’s Syndrome were recruited for this study. In addition, fertile women and healthy donors were used as control groups. The study also created endometrial organoids from affected patients and healthy women. These organoids - which are miniaturised endometria generated in the laboratory - showed features similar to those of endometrial tissue in vivo, suggesting that these organoids are a good in vitro model to study Asherman’s Syndrome.

In this study, more than 200,000 cells from the endometrium of patients with Asherman’s Syndrome and healthy controls were analysed. By incorporating cutting-edge machine learning models, the research team deciphered transcriptomic differences between in vivo and in vitro endometrial cells from controls and patients, providing further insight into alterations of the endometrial microenvironment in the disease.

These patients are part of an ongoing clinical study, currently in phase I/II, that seeks to validate the effects of therapy with stem cells from the patients’ own bone marrow (CD133+) on their reproductive clinical results.

Article reference:

Santamaria, X., Roson, B., Perez-Moraga, R. et al. Decoding the endometrial niche of Asherman’s Syndrome at single-cell resolution. NatCommun 14, 5890 (2023). https://doi.org/10.1038/s41467­’023 -41656-1