MATERNOEMBRYONIC TRANSFUSION AND CONGENITAL-MALFORMATIONS

There is an increasing number of reports relating chorionic villus sam pling (CVS) to transverse limb reduction defects or the oromandibular limb hypogenesis complex. Tn addition, a correlation has been establis hed between the severity of the defect and the gestational age when CV S is performed. Several hypotheses have been proposed for the increase d incidence of congenital malformations after CVS including vascular d isruption. Recently, it has been suggested that maternoembryonic trans fusion can occur after CVS and that this can lead to a local antibody- mediated reaction, followed by local pathogenetic cell degeneration, i .e., apoptotic cell death, due to vascular disruption. This increased apoptotic cell death will ultimately result in congenital malformation s. This paper describes an experimental model that can explain the pat hogenesis of congenital malformations after CVS. The model designed us es a whole rat embryo culture technique and intracardiac injection of antisera, mimicking transplacental transfusion after CVS. Injection of antibodies directed against blood group antigens is capable of induci ng increased apoptotic cell death. Immunological staining gives eviden ce of involvement of antibody-mediated reactions in the occurrence of apoptotic cell death. The dorsal aortae in 10-day-old rat embryos of 1 0-somite stages of development consist of a continuous endothelial cel l layer. The effect of intracardiac injection of antisera on the dorsa l aortae is only transient. Smaller vessels such as the pharyngeal arc h arteries or arteries of the limbs still have fenestrated endothelium and are therefore more vulnerable to the pathogenetic effect of the r eaction after transplacental transfusion causing vascular disruption. Development of the vascular pattern and differentiation of the vascula r wall reduce the risk of severe malformations later on in pregnancy, although the risk of malformations remains throughout pregnancy. Thus, intracardiac injection of antisera simulating maternoembryonic transf usion such as after CVS can lead to an antibody-mediated reaction with vascular disruption early in pregnancy inducing apoptotic cell death. Increased cell death may ultimately result in congenital malformation s, such as transverse limb defects or the oromandibular limb hypogenes is complex.