| Summary: | A mouse model has been established to investigate the teratogenic effects of amniotic sac puncture (ASP) performed during a similar period during gestation when chorionic villus sampling (cvs) would normally be carried out clinically. Many genes are expressed temporally and spatially in the interdigital zone during limb morphogenesis, and may play a key role of triggering the pre-set program within these areas. Of the latter, msx-1 is believed to maintain the proliferative and undifferentiated status of cells in the interdigital zones as well as being associated with the control of programmed cell death that occurs in these areas. Detection of the expression of msx-1 in the interdigital zones at intervals after ASP confirmed that this gene is upregulated in this area in the experimental autopods by 4h after ASP, and that this is accompanied by evidence of epithelial hypertrophy. This study demonstrated that msx-1 maintains the cells in the interdigital zones in a proliferative and undifferentiated state, as has been hypothesized by others, perhaps partly due to interference with epithelial-mesenchymal interaction. When Halothane, instead of Avertin was used as the anaesthetic during ASP, we have speculated that this could not only dramatically <I>reduce </I>the recovery time, but also improve the embryonic/fetal circulation to the autopod after ASP. Although similar overall rates of abnormalities were observed, the incidence of <I>syndactyly </I>was highly significantly reduced. This supported our hypothesis that venous stasis along with vascular disruption in the distal extremities may abolish the normal pre-set programs in the interdigital zones and influence the type of limb defects observed. In summary, if inadvertent rupture of the amnion occurs during the cvs procedure, fetal/embryonic venous stasis could occur as a secondary consequence of the compression of the embryo/fetus by uterine muscles and extraembryonic membranes. The induction of a similar range of limb defects in our mouse model to those observed clinically following cvs were investigated in this study. In addition, vascular disruption in the limbs following ASP was observed histologically, and it is suspected that this may be closely associated with the induction of syndactyly which was observed in more than 37% of the cases in this model.
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