The knowledge of chromosomal sex is important for large- scale analysis of gene expression

TitleThe knowledge of chromosomal sex is important for large- scale analysis of gene expression
Publication TypeJournal Article
Year of Publication2021
AuthorsLykhenko, OK, Obolenskaya, MY
Abbreviated Key TitleDopov. Nac. akad. nauk Ukr.
Date Published1/2021

The aim of the study was to determine the sex of the fetus in gene expression data lacking this information using expression of the Y-linked genes, and to elucidate the difference between sex-chromosomal-linked gene expression between placental samples with XX and XY genotypes during pregnacy. We have detected 27 differentially expressed sex-chromosomes-linked genes. We have shown that, in most cases, the expression of genes from X-chromosomes in pregnancy carrying baby girls is higher than in pregnancy carrying baby boys, but there are exceptions to this pattern, which must be taken into account in large-scale studies of gene expression. The nature of the difference in gene expression during pregnancy carrying baby girls and boys (positive or ne gative difference) persists during pregnancy, but the magnitude of the difference may remain unchanged or decrease from the first to the third trimester. Taking sex dimorphism into account when analyzing large-scale gene expression data between trimesters of pregnancy increases the number of differentially expressed genes, which improves the informative value of the study and is important for elucidating the pathogenesis of pregnancy complications associated with placental dysfunction.

Keywordshuman placenta, integrative analysis, sex, transcriptome

1. Di Renzo, G. C., Rosati, A., Sarti, R. D., Cruciani, L. & Cutuli, A. M. (2007). Does fetal sex affect pregnancy outcome? Gend. Med., 4, No. 1, pp. 19-30.
2. Peacock, J. L., Marston, L., Marlow, N., Calvert, S. A. & Greenough, A. (2012). Neonatal and infant outcome in boys and girls born very prematurely. Pediatr. Res., 71, No. 3, pp. 305-310.
3. Byrne, J. & Warburton, D. (1987). Male excess among anatomically normal fetuses in spontaneous abortions. Am. J. Med. Genet., 26, No. 3, pp. 605-611.
4. Lykhenko, O. K., Frolova, A. O. & Obolenskaya, M. Yu. (2017). Creation of gene expression database on preeclampsia-affected human placenta. Biopolym. Cell, 33, No. 6, pp. 442-452.
5. Buckberry, S., Bent, S. J., Bianco-Miotto, T. & Roberts, C. T. (2014). massiR: a method for predicting the sex of samples in gene expression microarray datasets. Bioinformatics, 30, No. 14, pp. 2084-2085.
6. Carrel, L. & Willard, H. F. (2005). X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature, 434, No. 7031, pp. 400-404.
7. Moreira de Mello, J. C., Fernandes, G. R., Vibranovski, M. D. & Pereira, L. V. (2017). Early X chromosome inactivation during human preimplantation development revealed by single-cell RNA-sequencing. Sci. Rep., 7, 10794.
8. Gonzalez, T. L., Sun, T., Koeppel, A. F., Lee, B., Wang, E. T., Farber, C. R., Rich, S. S., Sundheimer, L. W., Buttle, R. A., Chen, Y.-D. I., Rotter, J. I., Turner, S. D., Williams, J., Goodarzi, M. O. & Pisarska, M. D. (2018). Sex differences in the late first trimester human placenta transcriptome. Biol. Sex Differ., 9, No. 1, 4. 10.1186/s13293-018-0165-y
9. Garieri, M., Stamoulis, G., Blanc, X., Falconnet, E., Ribaux, P., Borel, C., Santoni, F. & Antonarakis, S. E. (2018). Extensive cellular heterogeneity of X inactivation revealed by single-cell allele-specific expression in human fibroblasts. Proc. Natl. Acad. Sci. USA, 115, No. 51, pp. 13015-13020. 10.1073/pnas.1806811115
10. Andrés, O., Kellermann, T., López-Giráldez, F., Rozas, J., Domingo-Roura, X. & Bosch, M. (2008). RPS4Y gene family evolution in primates. BMC Evol. Biol., 8, 142. 10.1186/1471-2148-8-142
11. Ni, W., Perez, A. A., Schreiner, S., Nicolet, C. M. & Farnham, P. J. (2020). Characterization of the ZFX family of transcription factors that bind downstream of the start site of CpG island promoters. Nucleic Acids Res., 48, No. 11, pp. 5986-6000. 10.1093/nar/gkaa384
12. Cortez, D., Marin, R., Toledo-Flores, D., Froidevaux, L., Liechti, A., Waters, P. D., Grützner, F. & Kaessmann, H. (2014). Origins and functional evolution of Y chromosomes across mammals. Nature, 508, No. 7497, pp. 488–493.
13. Pallares, P., Perez-Solana, M. L., Torres-Rovira, L. & Gonzalez-Bulnes, A. (2011). Phenotypic characterization by high-resolution three-dimensional magnetic resonance imaging evidences differential effects of embryo genotype on intrauterine growth retardation in NOS3-deficient mice. Biol. Reprod., 84, No. 5, pp. 866-871.
14. Younes, S. T., Maeda, K. J., Sasser, J. & Ryan, M. J. (2020). The glucagon-like peptide 1 receptor agonist liraglutide attenuates placental ischemia-induced hypertension. Am. J. Physiol. Heart Circ. Physiol., 318, No. 1, pp. H72-H77.