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LINE-1 retrotransposon methylation in chorionic villi of first trimester miscarriages with aneuploidy

  • Reproductive Physiology and Disease
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

High frequency of aneuploidy in meiosis and cleavage stage coincides with waves of epigenetic genome reprogramming that may indicate a possible association between epigenetic mechanisms and aneuploidy occurrence. This study aimed to assess the methylation level of the long interspersed repeat element 1 (LINE-1) retrotransposon in chorionic villi of first trimester miscarriages with a normal karyotype and aneuploidy.

Methods

The methylation level was assessed at 19 LINE-1 promoter CpG sites in chorionic villi of 141 miscarriages with trisomy of chromosomes 2, 6, 8–10, 13–15, 16, 18, 20–22, and monosomy X using massive parallel sequencing.

Results

The LINE-1 methylation level was elevated statistically significant in chorionic villi of miscarriages with both trisomy (45.2 ± 4.3%) and monosomy X (46.9 ± 4.2%) compared with that in induced abortions (40.0 ± 2.4%) (p < 0.00001). The LINE-1 methylation levels were specific for miscarriages with different aneuploidies and significantly increased in miscarriages with trisomies 8, 14, and 18 and monosomy X (p < 0.05). The LINE-1 methylation level increased with gestational age both for group of miscarriages regardless of karyotype (R = 0.21, p = 0.012) and specifically for miscarriages with trisomy 16 (R = 0.48, p = 0.007). LINE-1 methylation decreased with maternal age in miscarriages with a normal karyotype (R = − 0.31, p = 0.029) and with trisomy 21 (R = − 0.64, p = 0.024) and increased with paternal age for miscarriages with trisomy 16 (R = 0.38, p = 0.048) and monosomy X (R = 0.73, p = 0.003).

Conclusion

Our results indicate that the pathogenic effects of aneuploidy in human embryogenesis can be supplemented with significant epigenetic changes in the repetitive sequences.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgments

The molecular cytogenetic and molecular genetic studies were performed in the “Medical Genomics” Core Facility of the Tomsk National Research Medical Center of the Russian Academy of Sciences using the resources of the biocollection “Biobank of the population of northern Eurasia” of the Research Institute of Medical Genetics, Tomsk NRMC. We would like to thank all the families of our patients for their assistance with the clinical evaluation. We are grateful to all the clinicians who were involved in sample collection.

Funding

This study was supported by the Russian Science Foundation (project 19-74-10026).

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Authors and Affiliations

  1. Research Institute of Medical Genetics, Tomsk National Research Medical Center, Nab. R. Ushaiki, 10, Tomsk, Russia

    Stanislav A. Vasilyev, Ekaterina N. Tolmacheva, Oksana Yu. Vasilyeva, Anton V. Markov, Daria I. Zhigalina, Elena A. Sazhenova, Tatyana V. Nikitina, Anna A. Kashevarova & Igor N. Lebedev

  2. Biological Institute, National Research Tomsk State University, Lenina, 36, Tomsk, Russia

    Stanislav A. Vasilyev & Ekaterina S. Serdyukova

  3. Department of Medical Genetics, Siberian State Medical University, Moskovskiy Trakt, 2, Tomsk, Russia

    Lada A. Zatula, Vasilissa A. Lee & Igor N. Lebedev

Authors
  1. Stanislav A. Vasilyev
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  2. Ekaterina N. Tolmacheva
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  3. Oksana Yu. Vasilyeva
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  9. Elena A. Sazhenova
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  10. Tatyana V. Nikitina
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  11. Anna A. Kashevarova
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  12. Igor N. Lebedev
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Contributions

Conceptualization: Vasilyev S.A., Tolmacheva E.N., and Lebedev I.N.; methodology: Vasilyev S.A. and Markov A.V.; formal analysis and investigation: Vasilyev S.A., Tolmacheva E.N., Vasilyeva O. Yu., Markov A.V., Zhigalina D.I., Zatula L.A., Lee V.A., Serdyukova E.S., Sazhenova E.A., Nikitina T.V., and Kashevarova A.A.; writing (original draft preparation): Vasilyev S.A.; writing (review and editing): Vasilyev S.A., Tolmacheva E.N., Lebedev I.N., and Nikitina T.V.; funding acquisition: Vasilyev S.A.; and supervision: Lebedev I.N.

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Correspondence to Stanislav A. Vasilyev.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the local Research Ethics Committee of the Research Institute of Medical Genetics, Tomsk NRMC.

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Written informed consent was obtained from the parents of the patients for their participation.

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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 38, 139–149 (2021). https://doi.org/10.1007/s10815-020-02003-1

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