TITLE:
Effect of Lipopolysaccharide-Induced Immune Responses on Pregnancy Loss in Ewes
AUTHORS:
M. R. Graham, E. C. Bowdridge, S. A. Bowdridge, I. Holásková, T. H. Elsasser, R. A. Dailey
KEYWORDS:
Acute Phase Response, Pregnancy Loss, Sheep
JOURNAL NAME:
Open Journal of Animal Sciences,
Vol.8 No.4,
October
22,
2018
ABSTRACT: An acute phase response induced by Gram-negative
bacteria can reduce pregnancy rate. Early pregnant ewes were used to monitor
effects of lipopolysaccharide (LPS), an endotoxin
in the outer cell membrane of Gram-negative bacteria, on acute phase/innate
immunity response. In Exp. 1, mixed breed ewes were assigned to receive either
LPS or LPS and flunixin meglumine, an inhibitor of prostaglandin synthetase,
intravenously on day 5 after mating. In Exp. 2,
mixed breed ewes were assigned to receive an intravenous injection on day 5
after mating of either saline, LPS, recombinant human tumor necrosis factor
(TNF)-α or LPS after pretreatment
with dexamethasone. Pregnancy was diagnosed ultrasonographically on d 25, and
live births were recorded at parturition. Challenge with LPS induced acute
phase responses (fever, mucosal responses, lethargy and increased serum TNF,
haptoglobin andserum amyloid A) and decreased
pregnancy rates. Predictably, flunixin meglumine attenuated fever but did not
increase pregnancy rate in LPS-treated ewes. Similarly, exogenous TNF alone induced mucosal and serum amyloid
A responses but did not affect
pregnancy. Pre-treatment with dexamethasone blocked fever and mucosal and
lethargic responses and attenuated increases in TNF and haptoglobin but did not
ameliorate LPS-induced pregnancy loss. In summary, acute challenge
with LPS mimics bacterial-induced pregnancy losses in early pregnant ewes. Although
pretreatment with dexamethasone decreased clinical signs and some innate immune
responses, neither it nor flunixin meglumine prevented LPS-induced pregnancy
loss. That exogenous TNF alone did not promote pregnancy loss indicates that
other cytokines also contribute to LPS-induced embryonic loss.