Molecular and preclinical basis to inhibit PGE2 receptors EP2 and EP4 as a novel nonsteroidal therapy for endometriosis.

摘要: Endometriosis is a debilitating, estrogen-dependent, progesterone-resistant, inflammatory gynecological disease of reproductive age women. Two major clinical symptoms endometriosis are chronic intolerable pelvic pain and subfertility or infertility, which profoundly affect the quality life in Current hormonal therapies to induce hypoestrogenic state unsuccessful because undesirable side effects, health concerns, failure prevent recurrence disease. There fundamental need identify nonestrogen nonsteroidal targets for treatment endometriosis. Peritoneal fluid concentrations prostaglandin E2 (PGE2) higher women with endometriosis, this increased PGE2 plays important role survival growth lesions. The objective present study was determine effects pharmacological inhibition receptors, EP2 EP4, on molecular cellular aspects pathogenesis associated symptoms. Using human fluorescent endometriotic cell lines chimeric mouse model as preclinical testing platform, our results, knowledge first time, indicate that selective EP2/EP4: (i) decreases lesions; (ii) angiogenesis innervation (iii) suppresses proinflammatory dorsal root ganglia neurons decrease pain; (iv) proinflammatory, estrogen-dominant, progesterone-resistant environment endometrium (v) restores endometrial functional receptivity through multiple mechanisms. Our novel findings provide basis formulate long-term therapy