Effects of sex chromosome dosage on placental size in mice

Mice of the XO genotype with a paternally derived X chromosome ((XO)-O-p) have placental hyperplasia in late pregnancy, although in early pregnancy the ectoplacental cone, a placental precursor, is smaller in (XO)-O-p mice than in their XX sibs. This early size deficiency of the ectoplacental cone is apparently a consequence of X-p imprinting, because (XO)-O-m embryos (with a maternally derived X chromosome) are unaffected. In the present study we sought to establish whether (XO)-O-p placental hyperplasia in late pregnancy is also a consequence of X-p imprinting. Placental weight data were first collected from litters that included (XO)-O-p or (XO)-O-m fetuses and XX controls. Comparison of XO placentae with XX placentae showed that (XO)-O-p and (XO)-O-m placentae are hyperplastic. This finding suggested that the hyperplasia might be an X dosage effect, and this hypothesis was supported by the finding that XY male fetuses from the same crosses also had larger placentae than their XX sibs. Further analysis of a range of sex-chromosome variant genotypes, including X(m)YSry-negative females and XXSry transgenic males, showed that mouse fetuses with one X chromosome consistently had larger placentae than littermates with two X chromosomes, independent of their gonadal/androgen status.