Heterogeneous X inactivation in trophoblastic cells of human full-term female placentas

In female mammalian cells, one of the two X chromosomes is inactivated to c ompensate for gene-dose effects, which would be otherwise doubled compared with that in male cells. In somatic lineages in mice, the inactive X chromo some can be of either paternal or maternal origin, whereas the paternal X c hromosome is specifically inactivated in placental tissue. In human somatic cells, X inactivation is mainly random, but both random and preferential p aternal 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 po lymorphic androgen-receptor gene in full-term human female placentas. The s ites investigated are specifically methylated on the inactive X chromosome. No methylation was found in microdissected stromal tissue, whether from pl acenta or umbilical cord. Of nine placentas for which two closely apposed s amples were studied, X inactivation was preferentially maternal in three, w as preferentially paternal in one, and was heterogeneous in the remaining f ive. Detailed investigation of two additional placentas demonstrated region s with balanced (1:1 ratio) preferentially maternal and preferentially pate rnal X inactivation. No differences in ratio were observed in samples micro dissected to separate trophoblast and stromal tissues. We conclude that met hylation of the androgen receptor in human full-term placenta is specific f or trophoblastic cells and that the X chromosome can be of either paternal or maternal origin.