Embryonic mortality in cattle may occur because of inadequate inhibition of uterine secretion of prostaglandin (PG) F2α mediated by bovine interferon-τ (bIFN-τ). The objectives of the present study were to determine whether polyunsaturated fatty acids inhibit secretion of PGF2α from bovine endometrial cells induced by stimulating protein kinase C with phorbol 12,13 dibutyrate (PDBu) and to investigate possible mechanisms of action. Confluent cells were exposed for 24 h to 100 μM of linoleic, arachidonic (AA; C20:4, n-6), linolenic (LNA; C18:3, n-3), eicosapentaenoic (EPA; C20:5, n-3), or docosahexaenoic (DHA; C22:6, n-3) acid. After incubation, cells were washed and stimulated with PDBu. The EPA, DHA, and LNA attenuated secretion of PGF2α in response to PDBu. The EPA and DHA were more potent inhibitors than LNA. The EPA inhibited secretion of PGF2α at 6.25 μM. Secretion of PGF2α in response to PDBu decreased with increasing incubation time with EPA. Both bIFN-τ and EPA inhibited secretion of PGF2α, and their inhibitory effects were additive. The bIFN-τ, but not EPA, reduced the abundance of PG endoperoxide synthase-2 (PGHS-2) mRNA. Incubation with 100 μM EPA, DHA, or AA for 24 h followed by treatment with PDBu did not affect concentrations of PGHS-2 and phospholipase A2 proteins. The EPA and DHA inhibit secretion of PGF2α through a mechanism different from that of bIFN-τ. The effect of EPA on PGF2α secretion may be caused by competition with AA for PGHS-2 activity or reduction of PGHS-2 activity. The use of EPA and DHA to inhibit uterine secretion of PGF2α and to improve embryonic survival in cattle warrants further investigation.
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