Instability at microsatellite sequences in spontaneously aborted human embryos provides evidence for a novel...

Several factors have been proposed to confer a risk for abortion of the embryo. However, the aetiology of spontaneous abortions remains unclear. In the present study we investigated if an increased mutational rate occurs in the embryonic tissue and whether this phenomenon is associated with recurrent miscarriage. The mutational rate was assessed in 30 spontaneously aborted embryos using a bank of 8 highly polymorphic microsatellite markers, each one located on a different chromosome. The microsatellite sequences of DNA extracted from distal sites of each embryo were amplified by the polymerase chain reaction and the electrophoretic patterns were compared. Shifts in the mobility of the microsatellites indicating instability were scored for 12 among 30 (40%) specimens, thus suggesting that microsatellite instability (MI) is a relatively common feature of spontaneously aborted embryonic tissues. Association was found between instability and the absence of normal childbirth: 11 among 18 cases without a normal childbirth exhibited evidence of MI while only one among 12 cases with normal childbirth was positive for MI. Our results suggest that instability at microsatellite sequences which indicate decreased fidelity in DNA replication and repair are associated with the recurrent abortion of the embryo, particularly in cases without a normal childbirth.