COMMITMENT TO X-INACTIVATION PRECEDES THE TWINNING EVENT IN MONOCHORIONIC MZ TWINS

To gain insight into the timing of twinning, we have examined a closel y related event, X-chromosome inactivation, in female MZ twin pairs. X -inactivation patterns in peripheral blood and buccal mucosa were comp ared between monochorionic MZ (MC-MZ) and dichorionic MZ (DC-MZ) twins . Overall, the MC-MZ twins displayed highly similar X-inactivation pat terns, whereas DC-MZ twins frequently differed in their X-inactivation patterns, when both tissues were tested. Previous experimental data s uggest that commitment to X inactivation occurs when there are 10-20 c ells in the embryo. Simulation of embryo splitting after commitment to X inactivation suggests that MC-MZ twinning occurs three or four roun ds of replication after X inactivation, whereas a DC-MZ twinning event occurs earlier, before or around the time of X inactivation. Finally, the overall degree of skewing in the MZ twins was not significantly d ifferent from that observed in singletons. This indicates that X inact ivation does not play a direct role in the twinning process, and it fu rther suggests that extreme unequal splitting is not a common mechanis m of twin formation.