Inflammation-mediated fetal injury by maternal granulocyte-colony stimulating factor and high-dose intraamniotic endotoxin in the caprine model

To define a novel experimental model with maternal intravenous (i.v.) granulocyte-colony stimulating factor (G-CSF) followed by a single- and high-dose of 20 mg intra-amniotic (IA) endotoxin to induce fetal brain injury in the preterm fetal goat. Pregnant goats (n=4) were given 50 microg/day G-CSF into the maternal jugular vein through gestational days 110-115 (term, 150 days). At gestational day 115, 20 mg of IA endotoxin was administered. Following preterm delivery at day 120 by cesarean section umbilical cord, fetal lung and brain tissues were harvested for histopathology, immunohistochemistry, and electron microscopy. Inflammatory markers were evaluated in the amniotic fluid and fetal plasma. Necrotizing funisitis with abundant leukocyte infiltration and fetal brain injury was induced in all the fetuses in the experimental group. Maternal i.v. G-CSF for 5 days followed by 20 mg of IA endotoxin is a feasible caprine model to exacerbate intrauterine inflammation.