Methylation of the Retrotransposon LINE-1 Subfamilies in Chorionic Villi of Miscarriages

S. A. Vasilyev; Васильев С. А.; T. V. Nikitina; Никитина Т. В.; E. A. Sazhenova; Саженова Е. А.; I. V. Lushnikov; Лушников И. В.; O. Yu. Vasilyeva; Васильева О. Ю.; A. S. Ushakova; Ушакова А. С.; A. S. Zuev; Зуев А. С.; S. A. Filatova; Филатова С. А.; E. N. Tolmacheva; Толмачева Е. Н.; V. V. Demeneva; Деменева В. В.; I. N. Lebedev; Лебедев И. Н.

doi:10.31857/S0016675823120147

Methylation of the Retrotransposon LINE-1 Subfamilies in Chorionic Villi of Miscarriages

Authors: Vasilyev S.A.¹, Nikitina T.V.¹, Sazhenova E.A.¹, Lushnikov I.V.², Vasilyeva O.Y.¹, Ushakova A.S.¹^,2, Zuev A.S.¹, Filatova S.A.¹^,2, Tolmacheva E.N.¹, Demeneva V.V.¹, Lebedev I.N.¹
Affiliations:
1. Research Institute of Medical Genetics, Tomsk National Research Medical Center of Russian Academy of Sciences
2. National Research Tomsk State University
Issue: Vol 59, No 12 (2023)
Pages: 1419-1426
Section: ГЕНЕТИКА ЧЕЛОВЕКА
URL: https://journals.rcsi.science/0016-6758/article/view/233642
DOI: https://doi.org/10.31857/S0016675823120147
EDN: https://elibrary.ru/PQAIPV
ID: 233642

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Abstract

Miscarriage is potentially associated with abnormal epigenetic regulation of genes responsible for the development of the embryo and placenta. The aim of this work was to analyze the methylation level of various subfamilies of the LINE-1 retrotransposon, which makes up about 17% of the entire genome, in chorionic villi of spontaneous abortions of the first trimester of pregnancy with different karyotypes, including the most common aneuploidies. The methylation profile in the LINE-1 retrotransposon promoter was analyzed using targeted bisulfite massive parallel sequencing in chorionic villi of induced abortions (n = 39), spontaneous abortions with normal karyotype (n = 173), trisomy 16 (n = 62) and monosomy X (n = 46), and peripheral blood lymphocytes of healthy volunteers (n = 17). The level of methylation of the LINE-1 retrotransposon subfamilies in the control groups of adult lymphocytes and chorionic villi of induced abortions was the highest for evolutionarily young L1HS subfamilies, lower for the more ancient L1PA2 and L1PA3 subfamilies, and the lowest for the even more ancient L1PA4 subfamily. In the groups of spontaneous abortions, an increased level of LINE-1 methylation was observed, and this effect was more pronounced for the older LINE-1 subfamilies. The revealed patterns indicate less control over the older subfamilies of the LINE-1 retrotransposon in the human genome, which can potentially be used as regulatory elements for nearby genes involved in embryonic development. An increase in the level of methylation of such sequences can disrupt the development of the placenta and embryo and make a certain contribution to miscarriage.

Keywords

LINE-1 retrotransposon, DNA methylation, chorionic villi, miscarriage, aneuploidy, bisulfite sequencing, spontaneous abortions.

References

Quenby S., Gallos I.D., Dhillon-Smith R.K. et al. Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss // Lancet. 2021. V. 397. № 10285. P. 1658–1667. https://doi.org/10.1016/S0140-6736(21)00682-6
Li T.C., Makris M., Tomsu M. et al. Recurrent miscarriage: aetiology, management and prognosis // Hum. Reprod. Update. 2002. V. 8. № 5. P. 463–481. https://doi.org/10.1093/humupd/8.5.463
Red-Horse K., Zhou Y., Genbacev O. et al. Trophoblast differentiation during embryo implantation and formation of the maternal-fetal interface // J. Clin. Invest. 2004. V. 114. № 6. P. 744–754. https://doi.org/10.1172/JCI22991
Jauniaux E., Poston L., Burton G.J. Placental-related diseases of pregnancy: Involvement of oxidative stress and implications in human evolution // Hum. Reprod. Update. 2006. V. 12. № 6. P. 747–755. https://doi.org/:dml016
Shridhar V., Chu T., Simhan H. et al. High-resolution analysis of the human placental DNA methylome in early gestation // Prenat. Diagn. 2020. V. 40. № 4. P. 481–491. https://doi.org/10.1002/pd.5618
Robinson W.P., Price E.M. The human placental methylome // Cold Spring Harbor Perspect. Med. 2015. V. 5. № 5. https://doi.org/10.1101/cshperspect.a023044
Vlahos A., Mansell T., Saffery R. et al. Human placental methylome in the interplay of adverse placental health, environmental exposure, and pregnancy outcome // PLoS Genet. 2019. V. 15. № 8. https://doi.org/10.1371/journal.pgen.1008236
Etchegaray E., Naville M., Volff J.N. et al. Transposable element-derived sequences in vertebrate development // Mob. DNA. 2021. V. 12. № 1. P. 1. https://doi.org/10.1186/s13100-020-00229-5
Grow E.J., Flynn R.A., Chavez S.L. et al. Intrinsic retroviral reactivation in human preimplantation embryos and pluripotent cells // Nature. 2015. V. 522. № 7555. P. 221–225. https://doi.org/10.1038/nature14308
Reiss D., Zhang Y., Mager D.L. Widely variable endogenous retroviral methylation levels in human placenta // Nucl. Ac. Res. 2007. V. 35. № 14. P. 4743–4754. https://doi.org/10.1093/nar/gkm455
Lee J., Cordaux R., Han K. et al. Different evolutionary fates of recently integrated human and chimpanzee LINE-1 retrotransposons // Gene. 2007. V. 390. № 1–2. P. 18–27. https://doi.org/10.1016/j.gene.2006.08.029
Khan H., Smit A., Boissinot S. Molecular evolution and tempo of amplification of human LINE-1 retrotransposons since the origin of primates // Genome Res. 2006. V. 16. № 1. P. 78–87. https://doi.org/10.1101/gr.4001406
Boissinot S., Sookdeo A. The Evolution of LINE-1 in Vertebrates // Genome Biol. Evol. 2016. V. 8. № 12. P. 3485–3507. https://doi.org/10.1093/gbe/evw247
Vasilyev S.A., Tolmacheva E.N., Vasilyeva O.Y. et al. LINE-1 retrotransposon methylation in chorionic villi of first trimester miscarriages with aneuploidy // J. Assist. Reprod. Genet. 2021. V. 38. № 1. P. 139–149. https://doi.org/10.1007/s10815-020-02003-1
Lebedev I.N., Ostroverkhova N.V., Nikitina T.V. et al. Features of chromosomal abnormalities in spontaneous abortion cell culture failures detected by interphase FISH analysis // Eur. J. Hum. Genet. 2004. V. 12. № 7. P. 513–520. https://doi.org/10.1038/sj.ejhg.5201178
Vasilyev S.A., Timoshevsky V.A., Lebedev I.N. Cytogenetic mechanisms of aneuploidy in somatic cells of chemonuclear industry professionals with incorporated plutonium-239 // Russ. J. Genetics. 2010. V. 46. № 11. P. 1381–1385. https://doi.org/10.1134/s1022795410110141
Vasilyev S.A., Markov A.V., Vasilyeva O.Y. et al. Method of targeted bisulfite massive parallel sequencing of the human LINE-1 retrotransposon promoter // MethodsX. 2021. V. 8. https://doi.org/10.1016/j.mex.2021.101445
Fernandes J.D., Zamudio-Hurtado A., Clawson H. et al. The UCSC repeat browser allows discovery and visualization of evolutionary conflict across repeat families // Mob. DNA. 2020. V. 11. P. 13. https://doi.org/10.1186/s13100-020-00208-w
Zheng Y., Joyce B.T., Liu L. et al. Prediction of genome-wide DNA methylation in repetitive elements // Nucl. Ac. Res. 2017. V. 45. № 15. P. 8697–8711. https://doi.org/10.1093/nar/gkx587
Zadora J., Singh M., Herse F. et al. Disturbed placental imprinting in preeclampsia leads to altered expression of DLX5, a human-specific early trophoblast marker // Circulation. 2017. V. 136. № 19. P. 1824–1839. https://doi.org/10.1161/CIRCULATIONAHA.117.028110
Criscione S.W., Theodosakis N., Micevic G. et al. Genome-wide characterization of human L1 antisense promoter-driven transcripts // BMC Genomics. 2016. V. 17. P. 463. https://doi.org/10.1186/s12864-016-2800-5
Chishima T., Iwakiri J., Hamada M. Identification of transposable elements contributing to tissue-specific expression of long non-coding RNAs // Genes (Basel). 2018. V. 9. № 1. https://doi.org/10.3390/genes9010023
Pourrajab F., Hekmatimoghaddam S. Transposable elements, contributors in the evolution of organisms (from an arms race to a source of raw materials) // Heliyon. 2021. V. 7. № 1. https://doi.org/10.1016/j.heliyon.2021.e06029
Demeneva V.V., Tolmacheva E.N., Nikitina T.V. et al. Expression of the NUP153 and YWHAB genes from their canonical promoters and alternative promoters of the LINE-1 retrotransposon in the placenta of the first trimester of pregnancy // Vavil. Zh. Genet. Selektsii. 2023. V. 27. № 1. P. 63–71. https://doi.org/10.18699/VJGB-23-09