title: Maternoembryonic transfusion and congenital malformations.
abstract: There is an increasing number of reports relating chorionic villus sampling (CVS) to transverse limb reduction defects or the oromandibular limb hypogenesis complex. In addition, a correlation has been established between the severity of the defect and the gestational age when CVS is performed. Several hypotheses have been proposed for the increased incidence of congenital malformations after CVS including vascular disruption. Recently, it has been suggested that maternoembryonic transfusion 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 malformations. This paper describes an experimental model that can explain the pathogenesis of congenital malformations after CVS. The model designed uses 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 inducing increased apoptotic cell death. Immunological staining gives evidence of involvement of antibody-mediated reactions in the occurrence of apoptotic cell death. The dorsal aortae in 10-day-old rat embryos of 10-somite stages of development consist of a continuous endothelial cell layer. The effect of intracardiac injection of antisera on the dorsal aortae is only transient. Smaller vessels such as the pharyngeal arch arteries or arteries of the limbs still have fenestrated endothelium and are therefore more vulnerable to the pathogenetic effect of the reaction after transplacental transfusion causing vascular disruption. Development of the vascular pattern and differentiation of the vascular 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 transfusion 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 malformations, such as transverse limb defects or the oromandibular limb hypogenesis complex.
authors.affiliation: Department of Paediatric Surgery, University Children's Hospital, Wilhelmina Kinderziekenhuis, Utrecht, The Netherlands.
authors.forename: D C
authors.initials: DC
authors.lastname: van der Zee
authors.forename: K M
authors.initials: KM
authors.lastname: Bax
authors.forename: C
authors.initials: C
authors.lastname: Vermeij-Keers
mesh_terms: D000818:Animals; D015193:Chorionic Villi Sampling / Q000009:adverse effects*; D004195:Disease Models, Animal; D004622:Embryo, Mammalian / Q000002:abnormalities* / Q000276:immunology / Q000648:ultrastructure; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D007106:Immune Sera / Q000008:administration & dosage* / Q000276:immunology; D007150:Immunohistochemistry; D007267:Injections; D017880:Limb Deformities, Congenital; D008431:Maternal-Fetal Exchange / Q000276:immunology / Q000502:physiology*; D016253:Microscopy, Immunoelectron; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007106:Immune Sera