EXTL3-interacting endometriosis-specific serum factors induce colony formation of endometrial stromal cells

Endometriosis is a benign chronic condition characterized by the existence of endometrial-like stroma and glandular tissue in extrauterine locations. The molecular mechanisms of its pathogenesis have not been elucidated. We have studied the role of EXTL3 (exostosin-like 3) in endometriosis and found that it is expressed in endometrial tissue as well as endometriosis lesions. We have found that serum from endometriosis patients contains a factor or factors, which interact with EXTL3 resulting in strongly increased colony formation in regenerating cell culture. We also found increased anti-EXTL3 antibodies in endometriosis patients' sera. EXTL3 is an N-acetyl glucosamine (GlcNAc) transferase, performing a key step in heparan sulfate (HS) glucosaminoglycan synthesis. Many viruses replicate in regenerating epithelial cells and use HS as a receptor for cell entry. We measured antibody titres to viruses, which use HS as a receptor for cell entry, and found rarely increased titres for these viruses in endometriosis sera, whereas titres to viruses using other receptors were equally distributed in study groups. The data indicate that perturbation of HS metabolism is associated with endometriosis.