Maternally inherited X chromosome is not inactivated in mouse blastocysts due to parental imprinting

Mouse embryos having an additional maternally inherited X chromosome (X-M) invariably die before midgestation with the deficient extraembryonic ectode rm of the polar trophectoderm lineage, whereas postnatal mice having an add itional paternally inherited X chromosome (X-P) survive beyond parturition. A cytogenetic study led us to hypothesize that abnormal development of suc h embryos disomic for X-M (DsX(M)) is attributable to two doses of active X -M chromosome in extraembryonic tissues. To test the validity of this hypot hesis, we examined the initial X chromosome inactivation pattern in embryos at the blastocyst stage by means of replication banding method as well as RNA FISH detecting Xist transcripts. X-P was the only asynchronously replic ating X chromosome, if any, in (XXXP)-X-M-X-M blastocysts, and no such allo cyclic X chromosome was ever detected in (XXY)-X-M-Y-M blastocysts. In agre ement with these findings, only one Xist paint signal was detected in 79% o f (XXXP)-X-M-X-M cells, whereas no such signal was found in (XXY)-X-M-Y-M e mbryos. Thus, the present study supports the hypothesis that two X chromoso mes remaining active in the extraembryonic cell lineages due to the materna l imprinting explain the underdevelopment of extraembryonic structures and hence early postimplantation death of DsX(M) embryos.