Growth retardation and microcephaly induced in mice by placental infectionwith murine cytomegalovirus

Background: The placenta is regarded as a site of congenital cytomegaloviru s (CMV) infection. The placental infection of fetuses with murine CMV (MCMV ) was investigated in a mouse model. Methods: The placentas and fetuses were examined using the polymerase chain reaction (PCR) and Southern blotting for viral DNA and immunostaining for viral antigen. Since the transplacental infection rarely occurs, the placen tas were directly injected with MCMV at day 12.5 of gestation; the embryos were then allowed to develop until day 18.5 of gestation. Results: Formation of infected foci at day 18.5 of gestation was found in m ore than 60% of the injected placentas. Infection of about 50% of the embry os occurred from the infected placentas. The frequency of infection in the brain was 27%, which was the same as that in the liver and higher than that in the lungs. In the brains, infected cells were often observed in the ven tricular zone of the cerebrum and sometimes in the cortical plate and the h ippocampus. Developmental retardation with microcephaly was observed in abo ut 25% of offspring exposed to infection in utero. Conclusions: These results suggest that formation of infected foci in the p lacenta is important for embryonic congenital infection, and that the cereb ral ventricular zone is one of the most susceptible sites for CMV infection in the embryonic stage. Teratology 62:79-85, 2000. (C) 2000 Wiley-Liss, In c.