Effects of low-dose lipopolysaccharide (LPS) pretreatment on LPS-induced intra-uterine fetal death and preterm labor.
Lipopolysaccharide (LPS) has been associated with adverse developmental outcome, including embryonic resorption, intra-uterine fetal death (IUFD), intra-uterine growth retardation (IUGR) and preterm delivery in rodents. The purpose of the present study was to investigate whether administration of a low-dose LPS to the pregnant mice induce a reduced sensitivity to subsequent high-dose LPS-induced IUFD and preterm labor. We found that LPS-induced IUFD was obviously attenuated when the pregnant mice were pretreated with low-dose LPS (10 microg/kg, i.p.) 24h before high-dose LPS (120 microg/kg, i.p.). Consistent with its protective effect, when administered 24h before high-dose LPS, low-dose LPS pretreatment obviously inhibited the releases of tumor necrosis factor alpha (TNF-alpha) in maternal serum and amniotic fluid and attenuated LPS-induced placental lipid peroxidation and GSH depletion. However, when administered 4h before high-dose LPS, low-dose LPS pretreatment did not induced a reduced sensitivity to subsequent high-dose LPS-induced release of TNF-alpha in maternal serum and amniotic fluid. Actually, low-dose LPS pretreatment 4h before high-dose LPS worsened LPS-induced oxidative stress in mouse placenta and increased nitric oxide production in maternal serum and amniotic fluid. Correspondingly, low-dose LPS pretreatment 4h before high-dose LPS aggravated LPS-induced IUFD. Taken together, these results indicate that whether a low-dose LPS exposure during pregnancy produce LPS hyporesponsiveness depends on the interval between the two doses of LPS. When administered 24h before high-dose LPS, a low-dose LPS pretreatment induces a reduced sensitivity to subsequent high-dose LPS-induced IUFD, TNF-alpha production and oxidative stress.
Xu
De-Xiang
DX
Department of Toxicology, Anhui Medical University, Hefei, PR China. xudex@mail.hf.ah.cn
Wang
Hua
H
Zhao
Lei
L
Ning
Huan
H
Chen
Yuan-Hua
YH
Zhang
Cheng
C
D000818:Animals; D005260:Female; D005313:Fetal Death / Q000139:chemically induced*; D005978:Glutathione / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology* / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D009566:Nitrates / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D007752:Obstetric Labor, Premature / Q000139:chemically induced*; D018384:Oxidative Stress / Q000187:drug effects; D011247:Pregnancy; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D008070:Lipopolysaccharides; D009566:Nitrates; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D005978:Glutathione