In female mammalian cells, one of the two X chromosomes is inactivated to
compensate for gene-dose effects, which would be otherwise doubled
compared with that in male cells. In somatic lineages in mice, the
inactive X chromosome can be of either paternal or maternal origin,
whereas the paternal X chromosome is specifically inactivated in placental
tissue. In human somatic cells, X inactivation is mainly random, but both
random and preferential paternal X inactivation have been reported in
placental tissue. To shed more light on this issue, we used PCR to study
the methylation status of the polymorphic androgen-receptor gene in
full-term human female placentas. The sites investigated are specifically
methylated on the inactive X chromosome. No methylation was found in
microdissected stromal tissue, whether from placenta or umbilical cord. Of
nine placentas for which two closely apposed samples were studied, X
inactivation was preferentially maternal in three, was preferentially
paternal in one, and was heterogeneous in the remaining five. Detailed
investigation of two additional placentas demonstrated regions with
balanced (1:1 ratio) preferentially maternal and preferentially paternal X
inactivation. No differences in ratio were observed in samples
microdissected to separate trophoblast and stromal tissues. We conclude
that methylation of the androgen receptor in human full-term placenta is
specific for trophoblastic cells and that the X chromosome can be of
either paternal or maternal origin