Molecular and preclinical basis to inhibit PGE 2 receptors EP2 and EP4 as a novel nonsteroidal therapy for endometriosis

Joe A Arosh, JeHoon Lee, Dakshnapriya Balasubbramanian, Jone A Stanley, Charles R Long, Mary W Meagher, Kevin G Osteen, Kaylon L Bruner-Tran, Kaylon L. Bruner‐Tran, Robert C Burghardt, Anna Starzinski-Powitz, Anna Starzinski‐Powitz, Sakhila K Banu
Proceedings of the National Academy of Sciences of the United States of America · 2015 · vol. 112(31) , pp. 9716–9721 · doi:10.1073/pnas.1507931112 · PMID:26199416 · PMC4534219 · W1927345752
article OA: bronze CC0 ⤵ 62 in-corpus citations
📄 Open PDF View on OpenAlex View on PubMed View at publisher
⚙ AI-generated summary by claude@2026-06, 2026-06-07 ⓘ

Selective inhibition of PGE2 receptors EP2 and EP4 decreases lesion growth, angiogenesis, innervation, pain, and inflammation while restoring endometrial receptivity in preclinical endometriosis models.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

Abstract

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

My notes (saved in your browser only)

Condition tags

endometriosischronic_pelvic_paininfertility

MeSH descriptors

Endometriosis Endometriosis Receptors, Prostaglandin E, EP2 Subtype Receptors, Prostaglandin E, EP4 Subtype Animals Apoptosis Apoptosis Biphenyl Compounds Biphenyl Compounds Biphenyl Compounds Caspase 3 Caspase 3 Cell Line Cell Movement Cell Movement Cell Survival Cell Survival Disease Models, Animal Endometriosis Endometrium

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (38)

Cited by (50)

Source provenance

europepmc
last seen: 2026-06-13T06:22:48.782012+00:00
openalex
last seen: 2026-06-10T17:14:06.276822+00:00
pubmed
last seen: 2026-05-13T22:17:46.044120+00:00
License: CC0 · commercial use OK