The Sphingosine 1-Phosphate Axis: an Emerging Therapeutic Opportunity for Endometriosis

Endometriosis is a common condition in women of reproductive age, but its current interventions are unsatisfactory. Recent research discovered a dysregulation of the sphingosine 1-phosphate (S1P) signaling pathway in endometriosis and showed a positive outcome by targeting it. The S1P axis participates in a series of fundamental pathophysiological processes. This narrative review is trying to expound the reported and putative (due to limited reports in this area for now) interactions between the S1P axis and endometriosis in those pathophysiological processes, to provide some perspectives for future research. In short, S1P signaling pathway is highly activated in the endometriotic lesion. The S1P concentration has a surge in the endometriotic cyst fluid and the peritoneal fluid, with the downstream dysregulation of its receptors. The S1P axis plays an essential role in the migration and activation of the immune cells, fibrosis, angiogenesis, pain-related hyperalgesia, and innervation. S1P receptor (S1PR) modulators showed an impressive therapeutic effect by targeting the different S1P receptors in the endometriosis model, and many other conditions resemble endometriosis. And several of them already got approval for clinical application in many diseases, which means a drug repurposing direction and a rapid clinical translation for endometriosis treatments.