Summary
A bioRxiv preprint reports gene-expression pathway changes after 24-hour drug exposures in human endometrial assembloids. The laboratory findings identify simvastatin and primaquine for further study, not as established endometriosis treatments.
A bioRxiv preprint reports that simvastatin and primaquine altered gene-expression pathways in laboratory models of human endometrial tissue. The researchers used assembloids—cultures combining endometrial epithelial cells and stromal fibroblasts—and analysed gene activity after 24-hour drug exposures. The results offer proof-of-concept for using the model to investigate candidate drugs; they are not evidence that either medicine treats endometriosis in people.
How the assembloid screening worked
The team formed assembloids in 96-well agarose molds using immortalized epithelial cells (12Z) and stromal fibroblast cells (iEc), and also worked with primary tissue from patients. Epithelial cells form the lining of the endometrium, while stromal cells make up its supporting tissue. Bringing both cell types together allows researchers to examine responses in a model that includes more than one component of the tissue.
The researchers tested ibuprofen, fenoprofen, primaquine and simvastatin. After 24 hours, they collected the assembloids and monolayer cultures, then used RNA sequencing to measure gene-expression changes. Gene-set enrichment analysis was used to identify pathways whose expression patterns shifted in a direction the researchers classified as a reversal of endometriosis-associated changes.
Pathway changes reported
Primaquine reversed the chemical carcinogenesis–reactive oxygen species pathway in assembloids, according to the analysis. Simvastatin reversed the cytokine–cytokine receptor interaction pathway in both epithelial and stromal cell lines. In stromal cell lines, it also reversed the pathway labelled cytoskeleton in muscle cells. Fenoprofen reversed the calcium-signalling pathway in stromal cell lines.
The authors report that simvastatin produced the most significant gene-expression changes. These results point to molecular responses that can be examined in further work, but a pathway shift is not the same outcome as reduced lesions, pain or other symptoms. The experiment measured gene expression after a short exposure; it did not test treatment in patients.
The report is a preprint, and its authors identify small sample size as a limitation. Further research would need to establish whether the observed changes are reproducible and relevant to disease outcomes before either drug could be considered a treatment candidate for clinical use.