title: Spontaneous pregnancy loss mediated by abnormal maternal inflammation in rats is linked to deficient uteroplacental perfusion.
abstract: Abnormal maternal inflammation during pregnancy is associated with spontaneous pregnancy loss and intrauterine fetal growth restriction. However, the mechanisms responsible for these pregnancy outcomes are not well understood. In this study, we used a rat model to demonstrate that pregnancy loss resulting from aberrant maternal inflammation is closely linked to deficient placental perfusion. Administration of LPS to pregnant Wistar rats on gestational day 14.5, to induce maternal inflammation, caused fetal loss in a dose-dependent manner 3-4 h later, and surviving fetuses were significantly growth restricted. Pregnancy loss was associated with coagulopathy, structural abnormalities in the uteroplacental vasculature, decreased placental blood flow, and placental and fetal hypoxia within 3 h of LPS administration. This impairment in uteroplacental hemodynamics in LPS-treated rats was linked to increased uterine artery resistance and reduced spiral arteriole flow velocity. Pregnancy loss induced by LPS was prevented by maternal administration of the immunoregulatory cytokine IL-10 or by blocking TNF-α activity after treatment with etanercept (Enbrel). These results indicate that alterations in placental perfusion are responsible for fetal morbidities associated with aberrant maternal inflammation and support a rationale for investigating a potential use of immunomodulatory agents in the prevention of spontaneous pregnancy loss.
authors.affiliation: Department of Anatomy and Cell Biology, Queen's University, Kingston, Ontario, Canada K7L3N6.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Renaud
authors.forename: Tiziana
authors.initials: T
authors.lastname: Cotechini
authors.forename: Jill S
authors.initials: JS
authors.lastname: Quirt
authors.forename: Shannyn K
authors.initials: SK
authors.lastname: Macdonald-Goodfellow
authors.forename: Maha
authors.initials: M
authors.lastname: Othman
authors.forename: Charles H
authors.initials: CH
authors.lastname: Graham
mesh_terms: D000022:Abortion, Spontaneous / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D004195:Disease Models, Animal; D020964:Embryo Loss / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005313:Fetal Death / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics / Q000276:immunology; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D014599:Uterus / Q000098:blood supply*
chemical_list: D008070:Lipopolysaccharides