Differential Effects of n-3 and n-6 Fatty Acids on Prostaglandin F2α Production by Bovine Endometrial Cells

Abstract

Recent studies have implicated n-3 polyunsaturated fatty acids in the reduction of eicosanoid production in the bovine uterus. The objective of this study was to determine whether the effect of eicosapentaenoic acid (EPA; C20:5, n-3) on PGF2α production by bovine endometrial (BEND) cells is influenced by the quantity of linoleic acid (C18:2, n-6) in the incubation medium. Confluent BEND cells were incubated in the absence (control) or presence of 100μMof EPA for 24h. After incubation, cells were rinsed and then stimulated with phorbol 12,13-dibutyrate (PDBu; 100 ng/mL) for 6h. Additional sets of culture dishes were treated with a combination of EPA and increasing n-6/n-3 fatty acid ratios for 24h and then challenged with PDBu for 6h. The PDBu stimulated PGF2α secretion and upregulated steady-state concentrations of prostaglandin endoperoxide synthase-2 and peroxisome proliferator-activated receptor delta mRNA within 6h. Preincubation of BEND cells with EPA for 24h decreased PGF2α response to phorbol ester, but had no detectable effects on prostaglandin endoperoxide synthase-2 or peroxisome proliferator-activated receptor delta mRNA abundance in PDBu-stimulated BEND cells. The inhibitory effect of EPA on PGF2α production was reverted in BEND cells treated with an increasing n-6-to-n-3 fatty acid ratio. Findings indicate that the net inhibition of endometrial PGF2α bioynthesis by n-3 fatty acids may vary depending on the ratio of n-6 to n-3 fatty acids in the uterus.