Evolution of the Placental Barrier to Fetal Infection by Murine Enteroviruses

Abstract

A murine model that demonstrated a placental barrier to fetal enterovirus infection in late pregnancy was extended to middle and early gestation. Inoculation with Theiler's murine encephalomyelitis virus (TMEV) in middle and early gestation infected 73% and 90% of placentas and 7% and 78% of fetuses, respectively. In situ hybridization (ISH) of tissues obtained after middle-gestation inoculation revealed TMEV in the placental decidua and spongiotrophoblast layers but generally not in the labyrinth (the layer adjacent to the fetus) or fetus (similar to late gestation). In contrast, ISH of placentas harvested after early-gestation inoculation identified TMEV predominantly in the labyrinth, in which vasculature was often replaced by hyalinized hemorrhagic tissue and small cell infiltrates; fetuses contained virus in heart, pericardium, great vessels, lung, pleura, brain, and liver. The placental barrier to enterovirus transmission appears to develop between early and middle gestation. Enterovirus infection before this time may induce placental damage, fetal infection, or both.