Marked Stimulation Of The Lipoxin A4 Synthesis Pathway During Endometrial Stromal Decidualization In Women With And Without Endometriosis Suggests A Role In Early Pregnancy.

Lipoxin A4 (LXA4) is an anti-inflammatory and pro-resolution eiconsanoid, produced by sequential actions of the enzymes ALOX15B and ALOX5. We have previously shown cycle-regulation of these enzymes in the epithelial cells as well as increased expression in endometriosis. We hypothesized that LXA4 could play an important anti-inflammatory role in early pregnancy and endometriosis might alter the expression of the biosynthetic enzymes. Therefore, the objective of these studies was to determine the effects of decidualization on ALOX15B and ALOX5 expression in stromal cells from women with and without endometriosis. In vitro assays of cultured tissue from human subjects. Endometrial stromal cells obtained from endometrial biopsy in women with or without endometriosis were isolated by enzymatic digestion. Cells were decidualized for 7 days using estradiol (10-8M), medroxyprogesterone acetate (10-6M), and dibutyryl cAMP (0.1mM). Relative ALOX15B and ALOX5 mRNA expression was determined prior to and after treatment by real-time RT-PCR. Differences were assessed using a Mann-Whitney test. Decidualization of endometrial stromal cells profoundly increased the expression of ALOX15B in both control subjects and those with endometrosis (p=0.05, p=0.04). Endometrial stroma from subjects with endometriosis had increased expression of ALOX15B both at baseline and when decidualized compared to controls (p=0.02, p=0.03). Interestingly, no significant change in ALOX5 expression was associated with endometriosis or decidualization. The decidualization of endometrial stromal cells profoundly increases the expression of ALOX15B but has little effect on ALOX5. The effects of decidualization on ALOX15B are increased in women with endometriosis. Therefore, ALOX15B (and LXA4 synthesis) may be important in early pregnancy. The effects of increased expression in endometriosis remain unclear, but we speculate dysregulation may be a factor in the associated infertility.