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 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.
Looijenga
L H
LH
Laboratory for Experimental Patho-Oncology, Daniel den Hoed Cancer Center/Pathology, Josephine Nefkens Institute, FGG/EUR, Rotterdam, The Netherlands. looijenga@leph.azr
Gillis
A J
AJ
Verkerk
A J
AJ
van Putten
W L
WL
Oosterhuis
J W
JW
D019175:DNA Methylation; D004303:Dosage Compensation, Genetic; D005260:Female; D006801:Humans; D008297:Male; D010920:Placenta / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D011944:Receptors, Androgen / Q000235:genetics* / Q000378:metabolism; D014327:Trophoblasts
D011944:Receptors, Androgen