ArticleProceedings of the National Academy of Sciences of the United States of America2015
Molecular and preclinical basis to inhibit PGE2 receptors EP2 and EP4 as a novel nonsteroidal therapy for endometriosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 84 citations in OpenAlex.
- Molecular Insights Into Endometriosis for Early Detection and Therapeutic Targets.Reproductive sciences (Thousand Oaks, Calif.) · 2026Review
- Hormonal Dysregulation and Neuroinflammation in Endometriosis: Convergent Druggable Pathways.Current issues in molecular biology · 2026Review
- Prenatal bisphenol A exposure reprograms SF1-lactylation pathways to promote endometriosis susceptibility.iScience · 2026Article
- Mechanisms driving resistance to oxidative stress during endometrial stromal cell decidualization†.Biology of reproduction · 2026Review
- Impact of hysteroscopy on pregnancy outcomes in women with endometriosis-associated infertility undergoing their first frozen-thawed embryo transfer: a retrospective cohort study.Frontiers in medicine · 2026Article
- Macrophages in endometriosis: key roles and emerging therapeutic opportunities-a narrative review.Reproductive biology and endocrinology : RB&E · 2025Review
- WERF Endometriosis Phenome and Biobanking Harmonisation Project for Experimental Models in Endometriosis Research (EPHect-EM-Heterologous): heterologous rodent models.Molecular human reproduction · 2025Review
- WERF Endometriosis Phenome and Biobanking Harmonisation Project for Experimental Models in Endometriosis Research (EPHect-EM-Pain): methods to assess pain behaviour in rodent models of endometriosis.Molecular human reproduction · 2025Review
- Endometriosis and ovulatory menstruation: beyond the Sampson principle.The Journal of clinical investigation · 2025Review
- Progressively Diminished Prostaglandin E2 Signaling in Concordance with Increasing Fibrosis in Ectopic Endometrium.Reproductive sciences (Thousand Oaks, Calif.) · 2025Article
- Molecular Basis of Impaired Decidualization in the Eutopic Endometrium of Endometriosis Patients.Cells · 2025Review
- Modelling Endometriosis Using In Vitro and In Vivo Systems.International journal of molecular sciences · 2025Review
- EZH2 promotes endometriosis progression through estrogen receptor and TNFα expression.Frontiers in endocrinology · 2025Article
- Evodiamine suppresses endometriosis development induced by early EBV exposure through inhibition of ERβ.Frontiers in pharmacology · 2024Article
- Review
- Lysophospholipid Mediators in Health and Disease.Annual review of pathology · 2022Review
- Endometriosis-associated infertility: From pathophysiology to tailored treatment.Frontiers in endocrinology · 2022Review
- Higher fibrotic content of endometriotic lesions is associated with diminished prostaglandin E2 signaling.Reproductive medicine and biology · 2022Article
- Changing prostaglandin E2 (PGEReproductive medicine and biology · 2022Article
- Use of selective PGE2 receptor antagonists on human endometriotic stromal cells and peritoneal macrophages.Molecular human reproduction · 2021Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
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.
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