Expression of eicosanoid biosynthetic and catabolic enzymes in peritoneal endometriosis

J. C. Lousse, J-C Lousse, Sylvie Defrère, S Defrère, S Colette, A Van Langendonckt, Anne Van Langendonckt, J Donnez, Jacques Donnez
Human Reproduction · 2009 · vol. 25(3) , pp. 734–741 · doi:10.1093/humrep/dep408 · PMID:20023295 · W2123895053
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This study quantified eicosanoid enzyme expression in endometriosis patients, finding increased sPLA2-IIA, COX-2, and mPGES-1 in peritoneal macrophages and lesions, and decreased 15-PGDH in eutopic endometrium, suggesting an eicosanoid imbalance.

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Abstract

BACKGROUND: Increased peritoneal eicosanoid concentrations have been reported in endometriosis patients and might be important in disease-associated pain and inflammation. Here, we evaluated the expression of key biosynthetic and catabolic enzymes involved in this abnormal eicosanoid production in peritoneal macrophages and endometriotic lesions. METHODS: Peritoneal macrophages, endometriotic lesions and matched eutopic endometrium were collected from endometriosis patients (n = 40). Peritoneal macrophages and eutopic endometrium samples were also collected from disease-free women (n = 25). Expression of type IIA secretory phospholipase A(2) (sPLA(2)-IIA), cyclooxygenase-2 (COX-2), microsomal prostaglandin E synthase-1 (mPGES-1), 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and 5-lipoxygenase (5-LO) was quantified by real-time PCR, and these five key enzymes were localized by immunohistochemistry. RESULTS: sPLA(2)-IIA, COX-2 and mPGES-1 mRNA was significantly increased in peritoneal macrophages of endometriosis patients compared with controls (P = 0.006, P = 0.016 and P = 0.025, respectively). In endometriosis patients, sPLA(2)-IIA, mPGES-1 and 15-PGDH mRNA was significantly enhanced in peritoneal lesions compared with matched eutopic endometrium (P < 0.001, P < 0.001 and P = 0.005, respectively). In eutopic endometrium, a significant decrease in 15-PGDH mRNA was found in the endometriosis group compared with controls (P = 0.023). Finally, sPLA(2)-IIA, COX-2, mPGES-1 and 15-PGDH immunostaining was found mainly in endometrial glands, whereas 5-LO was distributed throughout the glands and stroma. CONCLUSIONS: Our study highlights an imbalance between eicosanoid biosynthesis and degradation in endometriosis patients. Both peritoneal macrophages and endometriotic lesions may be involved. Research into new molecules inhibiting biosynthetic enzymes (such as sPLA(2)-IIA and mPGES-1) and/or activating catabolic enzymes (such as 15-PGDH) may prove to be a major field of investigation in the development of targeted medical therapies.

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Condition tags

mesh:D004715endometriosis

MeSH descriptors

Eicosanoids Endometriosis Endometrium Adult Arachidonate 5-Lipoxygenase Arachidonate 5-Lipoxygenase Cyclooxygenase 2 Cyclooxygenase 2 Eicosanoids Endometriosis Endometrium Female Humans Hydroxyprostaglandin Dehydrogenases Hydroxyprostaglandin Dehydrogenases Intramolecular Oxidoreductases Intramolecular Oxidoreductases Macrophages, Peritoneal Macrophages, Peritoneal Metabolic Networks and Pathways

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