Skewed X-chromosome inactivation in human miscarriages

Abstract

The sex ratio in the first trimester of pregnancy shifts toward males due to increased elimination of female embryos. One reason for this phenomenon may be disruption of X chromosome inactivation. In this paper, we have analyzed the nature of the X chromosome inactivation in extraembryonic tissues of induced and spontaneous abortuses with 46,XX karyotype. Both equiprobable and asymmetric inactivation have been found in chorionic cytotrophoblast from spontaneous and induced abortuses. In the extraembryonic mesoderm of the control group of embryos, only equiprobable inactivation has been found, whereas this parameter was shifted in 15% of spontaneous abortions. The highest incidence of the selective inactivation of one of the parent homologues was found in the group with a lack of development of embryos and embryos from women with recurrent miscarriages. One of the reasons for the observed results can be compartmentalization of cells in the blastocyst leading to the nonrandom redistribution of cells and the predominance in the inner mass of cells with an active X chromosome with aberrations incompatible with normal embryonic development.