Abstract
Up-regulation of endometrial oxytocin receptor (OTR) expression followed by an increase in pulsatile endometrial prostaglandin (PG) F(2alpha) secretion causes luteolysis in cattle. Inhibition of luteolysis is essential for the maternal recognition of pregnancy but also occurs in association with endometritis. The factors regulating OTR expression at this time are unclear. The OTR gene promoter region contains binding elements for acute phase proteins but their function has not been established. This study investigated the effects of various cytokines on OTR expression and on PGF(2alpha) and PGE(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 early luteolysis (mean day of cycle 16.4+/-0.24) as determined by the initial concentration of endometrial OTR. Explants were treated for 48 h with: (i) lipopolysaccharide (LPS) and/or dexamethasone (DEX), (ii) ovine interferon-tau (oIFN-tau), or (iii) human recombinant interleukin (IL)-1alpha, -2 or -6. OTR mRNA was then measured in the explants by in situ hybridisation and the medium was collected for measurement of PGF(2alpha) and PGE(2) by RIA. LPS treatment stimulated production of PGF(2alpha), whereas DEX either alone or in combination with LPS was inhibitory to both PGF(2alpha) and PGE(2). Neither of these treatments altered OTR mRNA expression. oIFN-tau reduced OTR mRNA expression but stimulated production of both PGF(2alpha) and PGE(2). In endometrial samples collected in the late luteal phase, IL-1alpha, -2 and -6 all inhibited OTR mRNA expression, but IL-1alpha and -2 both stimulated PGF(2alpha) production. In contrast, when endometrium was collected in early luteolysis, none of the interleukins altered OTR expression or caused a significant stimulation of PGF(2alpha) production but IL-2 increased PGE(2). Neither IL-1alpha nor -2 altered OTR promoter activity in Chinese hamster ovary cells transfected with a bovine OTR promoter/chloramphenicol acetyl transferase reporter gene construct. In conclusion, the action of interleukins on both OTR mRNA expression and endometrial prostaglandin production alters around luteolysis. Pro-inflammatory interleukins suppress OTR expression in the late luteal phase, while LPS stimulates PGF(2alpha) without altering OTR mRNA expression. IL-I and -2 and LPS are therefore unlikely to initiate luteolysis but may cause raised production of PGF(2alpha) during uterine infection.
Highlights
Luteal regression in non-pregnant cows involves the action of oxytocin on endometrial oxytocin receptors (OTR) stimulating pulsatile secretion of prostaglandin (PG) F2 by the endometrium (Flint et al 1994, Thatcher et al 1995, Wathes & Lamming 1995)
In this study we have investigated the possible roles of various interleukins and LPS in the luteolytic process using a bovine endometrial explant culture system
IL-1 mRNA is present in the endometrium of both www.endocrinology.org pregnant and non-pregnant cows on day 16 after oestrus (Leung et al 2000)
Summary
Luteal regression in non-pregnant cows involves the action of oxytocin on endometrial oxytocin receptors (OTR) stimulating pulsatile secretion of prostaglandin (PG) F2 by the endometrium (Flint et al 1994, Thatcher et al 1995, Wathes & Lamming 1995). In early pregnancy endometrial OTR expression is suppressed by interferontau (IFN- ), which is secreted by the bovine blastocyst from day 8 of gestation, with production peaking on days 17–19 declining rapidly (Roberts et al 1992). In pregnant cows the episodes of PGF2 still occur but their amplitude is much reduced (Parkinson & Lamming 1990). In the pregnant ewe basal secretion of endometrial PGF2 is higher than in non-pregnant animals (Zarco et al 1988, Journal of Endocrinology (2001) 168, 497–508 0022–0795/01/0168–497 2001 Society for Endocrinology Printed in Great Britain
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