Genetic and developmental analysis of X-inactivation in interspecific hybrid mice suggests a role for the Y chromosome in placental dysplasia

It has been shown previously that abnormal placental growth, i.e, hyper- an d hypoplasia, occurs in crosses and backcrosses between different mouse (Mu s) species. A locus that contributes to this abnormal development has been mapped to the X chromosome. Unexpectedly, an influence of fetal sex on plac ental development has been observed, in that placentas attached to male fet uses tended to exhibit a more pronounced phenotype than placentas attached to females. Here, we have analyzed this sex dependence in more derail. Our results show that differences between male and female placental weights are characteristic of interspecific matings and are not observed in intraspeci fic Mus musculus matings. The effect is retained in congenic lines that con tain differing lengths of M. spretus-derived X chromosome. Expression of th e X-linked gene Pgk1 from the maternal allele only and lack of overall acti vity of two paternally inherited X-linked transgenes indicate that reactiva tion or lack of inactivation of the paternal X chromosome in trophoblasts o f interspecific hybrids is not a frequent occurrence. Thus, the difference between male and female placentas seems not to be caused by faulty preferen tial X-inactivation. Therefore, these data suggest that the sex difference of placental weights in interspecific hybrids is caused by interactions wit h the Y chromosome.