The effects of lipopolysaccharide and interleukins-1 alpha,-2 and-6 on oxytocin receptor expression and prostaglandin production in bovine endometrium

Up-regulation of endometrial oxytocin receptor (OTR) expression followed by an increase in pulsatile endometrial prostaglandin (PG) F-2 alpha secretio n causes luteolysis in cattle. Inhibition of luteolysis is essential for th e maternal recognition of pregnancy but also occurs in association with end ometritis. The factors regulating OTR expression at this time are unclear. The OTR gene promoter region contains binding elements for acute phase prot eins but their function has not been established. This study investigated t he effects of various cytokines on OTR expression and on PGF(2 alpha) and P GE(2) production in explant cultures of bovine endometrium. Endometrium was collected in the late luteal phase (mean day of cycle 15.4 +/- 0.50) or ea rly luteolysis (mean day of cycle 16.4 +/- 0.24) as determined by the initi al concentration of endometrial OTR. Explants were treated for 48 h with: ( i) lipopolysaccharide (LPS) and/or dexamethasone (DEX), (ii) ovine interfer on-tau (oIFN-tau), or (iii) human recombinant interleukin (IL)-1 alpha, -2 or -6. OTR mRNA was then measured in the explants by in situ hybridisation and the medium was collected for measurement of PGF(2 alpha) and PGE(2) by RIA. LPS treatment stimulated production of PGF(2 alpha), whereas DEX eithe r alone or in combination with LPS was inhibitory to both PGF(2 alpha) and PGE(2). Neither of these treatments altered OTR mRNA expression. oIFN-tau r educed OTR mRNA expression but stimulated production of both PGF(2 alpha) a nd PGE,. In endometrial samples collected in the late luteal phase, IL-1 al pha, -2 and -6 all inhibited OTR mRNA expression, but IL-1 alpha and -2 bot h stimulated PGF(2 alpha) production. In contrast, when endometrium was col lected in early luteolysis, none of the interleukins altered OTR expression or caused a significant stimulation of PGF(2 alpha) production but IL-2 in creased PGE(2). Neither IL-1 alpha nor -2 altered OTR promoter activity in Chinese hamster ovary cells transfected with a bovine OTR promoter/chloramp henicol acetyl transferase reporter gene construct. In conclusion, the acti on of interleukins on both OTR mRNA expression and endometrial prostaglandi n production alters around luteolysis. Pro-inflammatory interleukins suppre ss OTR expression in the late luteal phase, while LPS stimulates PGF(2 alph a) without altering OTR mRNA expression. IL-1 and -2 and LPS are therefore unlikely to initiate luteolysis but may cause raised production of PGF(2 al pha) during uterine infection.