Polyunsaturated Fatty Acids and Bovine Interferon-τ Modify Phorbol Ester-Induced Secretion of Prostaglandin F2α and Expression of Prostaglandin Endoperoxide Synthase-2 and Phospholipase-A2 in Bovine Endometrial Cells1

Abstract

Embryonic mortality in cattle may occur because of inadequate inhibition of uterine secretion of prostaglandin (PG) F2alpha mediated by bovine interferon-tau (bIFN-tau). The objectives of the present study were to determine whether polyunsaturated fatty acids inhibit secretion of PGF2alpha 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 microM 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 PGF2alpha in response to PDBu. The EPA and DHA were more potent inhibitors than LNA. The EPA inhibited secretion of PGF2alpha at 6.25 microM. Secretion of PGF2alpha in response to PDBu decreased with increasing incubation time with EPA. Both bIFN-tau and EPA inhibited secretion of PGF2alpha, and their inhibitory effects were additive. The bIFN-tau, but not EPA, reduced the abundance of PG endoperoxide synthase-2 (PGHS-2) mRNA. Incubation with 100 microM 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 PGF2alpha through a mechanism different from that of bIFN-tau. The effect of EPA on PGF2alpha 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 PGF2alpha and to improve embryonic survival in cattle warrants further investigation.

Effect of dietary enrichment with either n-3 or n-6 fatty acids on systemic metabolite and hormone concentration and ovarian function in heifers

“…In the current study, AA was highest in the plasma of animals supplemented with FO and this is consistent with other studies on plasma (Burns et al, 2003) and studies on milk (Mattos et al, 2002). AA is converted to PGH2, the precursor of the other prostaglandins, through the actions of the enzyme PGH synthase (PGHS; Mattos et al, 2003). Despite FO supplementation increasing systemic AA, there is evidence from this laboratory and others (Burns et al, 2003) that a high n-3 PUFA diet can reduce uterine endometrial tissue concentrations of AA.…”

“…Linolenic acid is the parent n-3 PUFA, with some limited elongation to the longer chain n-3 PUFA, EPA and DHA occurring. An in vitro study by Mattos et al (2003) showed linolenic acid to be effective in suppressing PGF 2a from phorbol ester-stimulated bovine endometrial (BEND) cells. Furthermore, cows supplemented with linolenic acid were shown to have had higher concentrations of oestradiol during the follicular phase of the oestrous cycle than unsupplemented cows (Robinson et al, 2002).…”

“…In vitro work by Mattos et al (2003) demonstrated that the addition of AA increased, while n-3 PUFA decreased the PGF 2a secretion of immortalised bovine endometrial cells. The ability to reduce the endometrial synthesis and secretion of the luteolysin, PGF 2a , during early pregnancy would be beneficial in the context of the successful establishment of pregnancy (Mattos et al, 2000).…”

Effects of short-term oilseed supplementation on plasma fatty acid composition, progesterone and prostaglandin F metabolite in lactating beef cows

“…Overall, PGFM concentrations did not differ by treatment and day, however, the difference observed for percentage change of concentrations of plasma PGFM on days 17 and 18 coincide with the increased plasma concentration of 20:4n-6 observed for FLX. This is in contrast to previous work where increasing the supply of n-3 fatty acids has been shown to decrease prostaglandin metabolite production (Mattos et al, 2003;Petit and Twagiramungu, 2006). The primary differences between the current experiment and published literature is likely the type of cattle used, in that most work with n-3 fatty acids was conducted with dairy-type cattle and various high-quality rations.…”

“…An increase in dietary 18:2n-6 will increase prostaglandin F (PGF 2 α) production (Lammoglia et al, 1997;Filley et al, 1999), which may negatively influence embryonic survival (Mattos et al, 2003) owing to decreases in progesterone (Diskin and Niswender, 1989). Progesterone plays a critical role in stimulating production of a variety of endometrial secretions that are necessary for successful embryonic development (Diskin and Morris, 2008).…”