Skewed X-chromosome inactivation in human miscarriages
- 37 Downloads
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.
Keywordsspontaneous abortuses anembryonic gestation X chromosome inactivation recurrent miscarriage
medical (induced) abortus
Unable to display preview. Download preview PDF.
- Allen, R.C., Zoghbi, H.Y., Moseley, A.B., Rosenblatt, H.M., and Belmont, J.W., Methylation of HpaII and HhaI sites near the polymorphic CAG repeat in the human androgen-receptor gene correlates with X chromosome inactivation, Am. J. Hum. Genet., 1992, vol. 51, no. 6 pp. 1229–5.PubMedCentralPubMedGoogle Scholar
- Lebedev, I.N., Kashevarova, A.A., Skryabin, N.A., Nikitina, T.V., Lopatkina, M.E., Melnikov, A.A., Sazhenova, E.A., Ivanova, T.V., and Evtushenko, I.D., The matrix comparative genomic hybridization (array-CGH) in the diagnosis of chromosomal imbalance, Zh. Akush. Zhen. Bol., 2013, vol. 62, no. 2 pp. 117–5.Google Scholar
- Moreira de Mello, J.C., de Araújo, E.S., Stabellini, R., Fraga, A.M., de Souza, J.E., Sumita, D.R., Camargo, A.A., and Pereira, L.V., Random X inactivation and extensive mosaicism in human placenta revealed by analysis of allelespecific gene expression along the X chromosome, PLoS One, 2010, vol. 5, pp. e10947.PubMedCentralCrossRefPubMedGoogle Scholar
- Orzack, S.H., Stubblefield, J.W., Akmaev, V.R., Colls, P., Munné, S., Scholl, T., Steinsaltz, D., and Zuckerman, J.E., The human sex ratio from conception to birth, Proc. Natl. Acad. Sci. USA, 2015. pii: 201416546.Google Scholar
- Peñaherrera, M.S, Jiang, R., Avila, L., Yuen, R.K., Brown, C.J., and Robinson, W.P., Patterns of placental development evaluated by X chromosome inactivation profiling provide a basis to evaluate the origin of epigenetic variation, Hum. Reprod., 2012, vol. 27, pp. 1745–4.PubMedCentralCrossRefPubMedGoogle Scholar
- Tolmacheva, E.N., Kashevarova, A.A., and Lebedev, I.N., The inactivation of the X chromosome and human pathology, Med. Genet., 2009, vol. 8, no. 9 pp. 9–5.Google Scholar
- Tolmacheva, E.N, Kashevarova, A.A, Sukhanova, N.N., Kharkov, V.N., and Lebedev, I.N., Asymmetric inactivation of the X chromosome in human embryos with mosaic trisomy of chromosome 16, Russ. J. Genet., 2011, vol. 43, no. 3 pp. 401–5.Google Scholar