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

Am J Hum Genet. 1999 May;64(5):1445-52. doi: 10.1086/302382.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Methylation
  • Dosage Compensation, Genetic*
  • Female
  • Humans
  • Male
  • Placenta / cytology
  • Placenta / metabolism
  • Pregnancy
  • Receptors, Androgen / genetics*
  • Receptors, Androgen / metabolism
  • Trophoblasts*


  • Receptors, Androgen