Advertisement

Cell and Tissue Biology

, Volume 10, Issue 1, pp 55–59 | Cite as

Skewed X-chromosome inactivation in human miscarriages

  • E. N. Tolmacheva
  • S. A. Vasil’ev
  • E. A. Sazhenova
  • D. I. Zhigalina
  • E. I. Grigorovich
  • T. V. Nikitina
  • A. A. Mel’nikov
  • E. S. Zhabina
  • T. V. Ivanova
  • I. D. Evtushenko
  • I. N. Lebedev
Article
  • 37 Downloads

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.

Keywords

spontaneous abortuses anembryonic gestation X chromosome inactivation recurrent miscarriage 

Abbreviations

EM

extraembryonic mesoderm

MA

medical (induced) abortus

SA

spontaneous abortus

CC

chorionic cytotrophoblast

XCI

X-chromosome inactivation

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 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
  2. Evdokimova, V.N., Nikitina, T.V., Lebedev, I.N., Sukhanova, N.N., and Nazarenko, S.A., On the question of the sex ratio in the early embryonic lethality in humans, Russ. J. Dev. Biol., 2000, vol. 31, no. 4 pp. 251–5.CrossRefGoogle Scholar
  3. Kuo, P.L., Huang, S.C., Chang, L.W., Lin, C.H., Tsai, W.H., and Teng, Y.N., Association of extremely skewed X-chromosome inactivation with taiwanese women presenting with recurrent pregnancy loss, J. Formosan Med. Assoc., 2008, vol. 107, pp. 340–4.CrossRefPubMedGoogle Scholar
  4. Lau, A.W., Brown, C.J., Penaherrera, M.S., Langlois, S., Kalousek, D.K., and Robinson, W.P., Skewed X-chromosome inactivation is common in fetuses or newborns associated with confined placental mosaicism, Am. J. Hum. Genet., 1997, vol. 61, pp. 1353–4.PubMedCentralCrossRefPubMedGoogle Scholar
  5. 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
  6. 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
  7. Mutter, G.L. and Boynton, K.A., PCR bias in amplification of androgen receptor alleles, a trinucleotide repeat marker used in clonality studies, Nucl. Acids Res., 1995, vol. 23, pp. 1411–4.PubMedCentralCrossRefPubMedGoogle Scholar
  8. Orstavik, K.H., Skewed X inactivation in healthy individuals and in different disease, Acta Pediatrica Suppl., 2006, vol. 95, pp. 24–4.CrossRefGoogle Scholar
  9. 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
  10. Ostroverkhova, N.V., Nazarenko, S.A., Lebedev, I.N., Cheremnykh, A.D., Nikitina, T.V., and Sukhanova, N.N., Detection of aneuploidy in spontaneous abortions by comparative genomic hybridization, Russ. J. Genet., 2002, vol. 38, no. 2 pp. 1690–5.CrossRefGoogle Scholar
  11. 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
  12. Plenge, R.M., Hendrich, B.D., Schwartz, C., Arena, J.F., Naumova, A., Sapienza, C., Winter, R.M., and Willard, H.F., A promoter mutation in the XIST gene in two unrelated families with skewed X-chromosome inactivation, Nat. Genet., 1997, vol. 17, pp. 353–4.CrossRefPubMedGoogle Scholar
  13. Sullivan, A.E., Lewis, T., Stephenson, M., Odem, R., Schreiber, J., Ober, C., and Branch, D.W., Pregnancy outcome in recurrent miscarriage patients with skewed X chromosome inactivation, Obstet. Gynecol., 2003, vol. 101, pp. 1236–4.CrossRefPubMedGoogle Scholar
  14. 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
  15. 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
  16. Uehara, S., Tamura, M., Nata, M., Ji, G., Yaegashi, N., Okamura, K., and Yajima, A., X-chromosome inactivation in the human trophoblast of early pregnancy, J. Hum. Genet., 2000, vol. 45, pp. 119–4.CrossRefPubMedGoogle Scholar
  17. Vasques, L.R., Klocker, M.N., and Pereira, L.V., X chromosome inactivation: how human are mice?, Cytogenet. Genome Res., 2002, vol. 99, pp. 30–4.CrossRefPubMedGoogle Scholar
  18. Zeng, S.M. and Yankowitz, J., X-inactivation patterns in human embryonic and extra-embryonic tissues, Placenta, 2003, vol. 24, pp. 270–4.CrossRefPubMedGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2016

Authors and Affiliations

  • E. N. Tolmacheva
    • 1
    • 2
  • S. A. Vasil’ev
    • 1
    • 2
  • E. A. Sazhenova
    • 1
  • D. I. Zhigalina
    • 2
  • E. I. Grigorovich
    • 2
  • T. V. Nikitina
    • 1
  • A. A. Mel’nikov
    • 1
  • E. S. Zhabina
    • 3
  • T. V. Ivanova
    • 3
  • I. D. Evtushenko
    • 3
  • I. N. Lebedev
    • 1
    • 2
    • 3
  1. 1.Research Institute of Medical GeneticsTomskRussia
  2. 2.National Research Tomsk State UniversityTomskRussia
  3. 3.Siberian State Medical University of the Russian Ministry of HealthTomskRussia

Personalised recommendations