Alteration of prostaglandin production and agonist responsiveness by n-6 polyunsaturated fatty acids in endometrial cells from late-gestation ewes

Abstract

We investigated the effect of n-6 polyunsaturated fatty acids (PUFAs) on prostaglandin (PG) production by the uterus. A mixed population of endometrial cells (epthelium and stroma) from late-gestation ewes were cultured in defined medium containing linoleic acid (LA, 18:2, n-6), γ-linolenic acid (GLA, 18:3, n-6) or arachidonic acid (AA, 20:4, n-6) in concentrations of 0 (control), 20 or 100 μM. After 45 h in test medium with or without added PUFAs, cells were challenged with control medium (CM), oxytocin (OT, 250 nM), lipopolysaccharide (LPS, 0·1 μg/ml) or dexamethasone (DEX, 5 μM) for 22 h in the continued presence of the same concentration of PUFA and the medium was collected for measurement of PGF2α and PGE2. Supplementation with LA inhibited the production of PGF2α but did not alter PGE2, whereas GLA and AA increased production of both PGs. All PUFA supplements thus increased the ratio of PGE2 to PGF2α (E:F ratio) two- to threefold. In control cells, OT and LPS challenges stimulated the production of PGF2α and PGE2. In all challenge groups, the concentrations of PGF2α in response to PUFAs followed the same pattern - LA