Eicosanoid Profiling of the Endometrium and Omental Adipose from Women with and without Endometriosis

Endometriosis is a chronic gynaecological condition, presenting with pain and sub fertility. Eicosanoids are produced bycyclooxygenases (COX) and lipoxygenases (LOX) and their activities in endometrial and omental tissue are of interest, yet few have been investigated in relation to the aetiology of endometriosis. The aim of this study was to profile the eicosanoids and related mediators from COX and LOX pathways in eutopicendometrium and omental adipose from women with and without endometriosis to elucidate their role in the aetiology of the disease.

Samples of paired eutopic endometrium and omental adipose were obtained from women who gave informed written consent prior to laparoscopic surgery at St Mary’s Hospital, Manchester. Samples were separated by diagnosis of endometriosis and analysed using liquid chromatography coupled to tandem mass spectrometry (UPLC/ESI-MS/MS) using an array of 77 lipid mediators (1). Here we present the most abundant eicosanoid species derivatives of dihomo-γ-linolenic acid (DGLA), arachidonic acid (AA) and eicosapentenoic acid (EPA).

Table 1. Eicosanoid profile in matched tissues (pg/mg protein) from women with (E)and without (NE)endometriosis. ND =Not detected. Data is presented as means ± S.E.M, * P<.05, ** P<0.01, cells in red highlight significant differences. Statistical analysis performed using Mann Whitney U test in SPSS.

Results from the mass spectrometry analysis detected 44 out of 77 mediators present in the endometrial tissues and 36 out of 77 mediators present in the omental fat. Significant decreases in the eicosanoids PGE2, PGD2, PGF2α, 13,14 dihydro 15-keto PGE2, PGE1, PGF1α, PGE3, 6-keto PGE1, 11-HETE, 12-HEPE were observed in the endometrium of women with endometriosis. No significant differences were observed in the omental fat between patients groups. Interestingly, 9 out of the 12 mediators found to be significantly decreased were products of the COX pathway, indicating a possible defect in the expression/regulation of these enzymes in the endometrium of women with endometriosis. Future work will quantify expression of COX and LOX enzymes and elucidate their roles in eutopic/ectopic endometrial growth and function. The balance of fatty acids may provide therapeutic insight in the future(2,3).

(1) Massey KA and Nicolaou A (2013) Free Radic Biol Med 59: 45-55

(2) Wathes DC et al. (2007) Biol Reprod 77(2): 190-201

(3) Hansen SO and Knudsen UB. (2013) Eur J Obstet Gynecol Reprod Bio 169(2): 162-71