Erythropoietin ameliorates damage to the placenta and fetal liver induced by exposure to lipopolysaccharide.
Intrauterine infection and inflammation have been causally linked to preterm birth and fetal brain injury. Using an ovine model of endotoxin-induced brain injury we have recently shown that recombinant human erythropoietin (rhEPO) reduces brain injury and protects against damage to myelination in major myelinated axon tracts. Our present objective was to determine whether rhEPO is also protective of the placenta and the fetal liver, organs which could influence fetal well-being. At 107 +/- 1 days of gestational age (DGA) chronically catheterized fetal sheep were randomly assigned to receive, on 3 consecutive days, either: 1) an i.v. bolus dose of lipopolysaccharide (LPS; approximately 0.9 microg/kg; n = 8); 2) i.v. bolus dose of LPS, followed at 1 h by 5000 IU/kg of rhEPO (LPS + rhEPO, n = 8); 3) rhEPO (n = 3). Seven untreated fetuses served as controls (n = 7). The placenta and fetal liver were examined histologically at 116 +/- 1 DGA; a placental injury index was formulated comprising measures of placental area, apoptosis, tissue injury and the size of the intervillous space. In LPS-exposed fetuses this index was greater than in control or rhEPO alone fetuses (p < 0.02). Treatment of LPS-exposed fetuses with rhEPO resulted in a reduction in the index (p < 0.05) and in the extent of liver necrosis. We conclude that rhEPO offers protection to the placenta and fetal liver in the presence of acute inflammation.
Dijkstra
F
F
Department of Anatomy and Cell Biology, University of Melbourne, Parkville 3010, Victoria, Australia.
Jozwiak
M
M
De Matteo
R
R
Duncan
J
J
Hale
N
N
Harding
R
R
Rees
S
S
D000818:Animals; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D005333:Fetus / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000517:prevention & control; D008070:Lipopolysaccharides / Q000009:adverse effects*; D008099:Liver / Q000187:drug effects*; D009336:Necrosis / Q000517:prevention & control; D010920:Placenta / Q000187:drug effects* / Q000473:pathology; D011247:Pregnancy; D011994:Recombinant Proteins; D012756:Sheep
D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D004921:Erythropoietin