X-chromosome inactivation in XX androgenetic mouse embryos surviving implantation

Using genetic and cytogenetic markers, we assessed early development and X- chromosome inactivation (X-inactivation) in XX mouse androgenones produced by pronuclear transfer. Contrary to the current view, XX androgenones are c apable of surviving to embryonic day 7.5, achieving basically random X-inac tivation in all tissues including those derived from the trophectoderm and primitive endoderm that are characterized by paternal X-activation in ferti lized embryos. This finding supports the hypothesis that in fertilized fema le embryos, the maternal X chromosome remains active until the blastocyst s tage because of a rigid imprint that prevents inactivation, whereas the pat ernal X chromosome is preferentially inactivated in extra-embryonic tissues owing to lack of such imprint. In spite of random X-inactivation in XX and rogenones, FISH analyses revealed expression of stable Xist RNA from every X chromosome in XX and XY androgenonetic embryos from the four-cell to moru la stage. Although the occurrence of inappropriate X-inactivation was furth er suggested by the finding that Xist continues ectopic expression in a pro portion of cells from XX and XY androgenones at the blastocyst and the earl y egg cylinder stage, a replication banding study failed to provide positiv e evidence for inappropriate X-inactivation at E6.5.