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Polyunsaturated Fatty Acids and Bovine Interferon- Modify Phorbol Ester-Induced Secretion of Prostaglandin F₂ and Expression of Prostaglandin Endoperoxide Synthase-2 and Phospholipase-A₂ in Bovine Endometrial Cells¹

Department of Animal Sciences, University of Florida, Gainesville, Florida 32611-0910

Embryonic mortality in cattle may occur because of inadequate inhibition of uterine secretion of prostaglandin (PG) F₂ mediated by bovine interferon- (bIFN-). The objectives of the present study were to determine whether polyunsaturated fatty acids inhibit secretion of PGF₂ 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 PGF₂ in response to PDBu. The EPA and DHA were more potent inhibitors than LNA. The EPA inhibited secretion of PGF₂ at 6.25 µM. Secretion of PGF₂ in response to PDBu decreased with increasing incubation time with EPA. Both bIFN- and EPA inhibited secretion of PGF₂, and their inhibitory effects were additive. The bIFN-, 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 PGF₂ through a mechanism different from that of bIFN-. The effect of EPA on PGF₂ 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 PGF₂ and to improve embryonic survival in cattle warrants further investigation.

¹ This research was supported in part by the NRI Competitive Grant Program/USDA, grant 98-35203-6367. This is Florida Agricultural Experimental Station Journal Series R-09552.

² Correspondence: William W. Thatcher, Department of Animal Sciences, University of Florida. P.O. Box 11910, Gainesville, Florida 32611-0910. FAX: 352 392 5595; thatcher{at}animal.ufl.edu

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