Webster W S
Department of Anatomy and Histology, University of Sydney, Australia.
Teratology. 1998 Jul;58(1):13-23. doi: 10.1002/(SICI)1096-9926(199807)58:1<13::AID-TERA5>3.0.CO;2-2.
It is apparent that there are many unanswered questions about the pathogenesis of CRS. For instance, the chance of embryonic infection decreases in the second semester only to increase again in the third trimester. This is presumably due to unspecified changes in the placenta. When the embryo is infected early in the first trimester it does not appear to have any conventional immunological response to prevent spread of the virus. Yet it has been suggested that only 1 in 10(3) to 10(5) of its cells become infected. If this is true, what controls the spread of the virus in the early embryo? Why does the virus not affect major morphogenetic processes? There is considerable evidence that the virus spreads through the vascular system of the infected fetus and the observed cardiovascular, CNS, and hearing defects may be primarily due to focal cytopathic damage to the walls of blood vessels and lining of the heart; subsequent organ infection and/or ischemia may lead to further damage. Damage to blood vessels is probably extensive throughout the fetus and may be the cause of the generalized growth retardation. The effects in the eye appear to be due to a direct cytopathic effect, particularly on the lens. The short susceptible period for cataract formation is consistent with the protective effect of the lens capsule. Deafness, cardiovascular and neurological damage, and retinopathy all occur when infection takes place in the first 16 weeks of gestation and are rare after this time, despite the absence of any obvious morphological or functional changes in the susceptible structures. This termination of susceptibility in the second trimester is consistent with development of the fetal immune response and increased transfer of maternal IgG. The effect on blood vessels in particular may be limited by antibody production, although existing endothelial infection and damage may be progressive. The fetus seems unable to rid itself of established intracellular virus. The causes of the well-established late manifestations remain unknown. If these serious late-appearing effects are due to prenatal damage, then it is possible that other human teratogens may also cause unexpected late symptoms. This should also be a concern in the area of animal reproductive toxicology testing.
