Abnormal methylation of PRDM16 and PTPRN2 genes in chorionic villi in miscarriage

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Abstract

Relevance. Abnormal epigenetic regulation of genes responsible for the development of the embryo and placenta is associated with many pregnancy pathologies. Aim. The aim of this work was to analyze the prevalence of abnormal methylation of the PRDM16 and PTPRN2 genes in chorionic villi of spontaneous abortions with normal karyotype and with the most frequent aneuploidies (trisomy 16 and monosomy X). Materials and Methods. The methylation profile was evaluated using targeted bisulfite massive parallel sequencing in chorionic villi of induced abortions (n = 10), spontaneous abortions with normal karyotype (n = 39), trisomy 16 (n = 17) and monosomy X (n = 20) and peripheral blood lymphocytes of healthy volunteers (n = 6). Results and Discussion. In analyzed genes, differential methylation of individual CpG sites was found in chorionic villi of spontaneous abortions. Despite the absence of significant differences between the groups in the average level of methylation in analyzed gene regions, abnormal methylation of the PRDM16 and PTPRN2 genes were detected for 33 % and 5 % of spontaneous abortions, respectively, indicating a high incidence of epigenetic abnormalities in these genes in the chorionic villi of spontaneous abortions. The level of methylation of the PRDM16 gene significantly correlated with the level of methylation of the retrotransposon LINE-1, which indicates the generalized nature of methylation disorders in spontaneous abortions. Finally, the level of methylation of the PTPRN2 gene depended on the age of mothers of spontaneous abortions with monosomy X, which raises the question of the influence of maternal factors on the methylation profile in this group of spontaneous abortions. Conclusion. The results indicate that epigenetic disorders of the PRDM16 gene may be associated with spontaneous termination of pregnancy in the first trimester.

About the authors

Stanislav A. Vasilyev

Tomsk National Research Medical Center; National Research Tomsk State University

Author for correspondence.
Email: stanislav.vasilyev@medgenetics.ru
ORCID iD: 0000-0002-5301-070X
SPIN-code: 8087-5222
Tomsk, Russian Federation

Oksana Yu. Vasilyeva

Tomsk National Research Medical Center

Email: stanislav.vasilyev@medgenetics.ru
ORCID iD: 0000-0001-5797-0014
SPIN-code: 3582-1273
Tomsk, Russian Federation

Bismark Oppong-Peprah

National Research Tomsk State University

Email: stanislav.vasilyev@medgenetics.ru
Tomsk, Russian Federation

Victoria V. Demeneva

Tomsk National Research Medical Center

Email: stanislav.vasilyev@medgenetics.ru
ORCID iD: 0000-0002-5315-4914
SPIN-code: 3631-0953
Tomsk, Russian Federation

Andrey S. Zuev

Tomsk National Research Medical Center

Email: stanislav.vasilyev@medgenetics.ru
ORCID iD: 0000-0001-9474-9335
SPIN-code: 3235-1754
Tomsk, Russian Federation

Elena A. Sazhenova

Tomsk National Research Medical Center

Email: stanislav.vasilyev@medgenetics.ru
ORCID iD: 0000-0003-3875-3932
SPIN-code: 8788-4112
Tomsk, Russian Federation

Tatiana V. Nikitina

Tomsk National Research Medical Center

Email: stanislav.vasilyev@medgenetics.ru
ORCID iD: 0000-0002-4230-6855
SPIN-code: 8941-1605
Tomsk, Russian Federation

Ekaterina N. Tolmacheva

Tomsk National Research Medical Center

Email: stanislav.vasilyev@medgenetics.ru
ORCID iD: 0000-0001-6427-3276
SPIN-code: 7837-4073
Tomsk, Russian Federation

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1. Fig. 1. The methylation profile of CpG sites in the analyzed region (indicated by red vertical stripes in the diagram) of the PTPRN2 gene in the groups of spontaneous abortions with trisomy 16 (SA Tri16), with monosomy X (SA MonoX) and with normal karyotype (SA NK) compared with the group of induced abortions (IA). Dotted lines show standard deviation of the methylation profile;* — p < 0.05

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2. Fig. 2. The methylation profile of CpG sites in the analyzed region (indicated by red vertical stripes in the diagram) of the PRDM16 gene in the groups of spontaneous abortions with trisomy 16 (SA Tri16), with monosomy X (SA MonoX) and with normal karyotype (SA NK) compared with the group of induced abortions (IA). Dotted lines show standard deviation of the methylation profile;* — p < 0.05

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3. Fig. 3. The average level of methylation of the analyzed CpG sites of the PTPRN2 and PRDM16 genes in chorionic villi in groups of spontaneous abortions with trisomy 16, with monosomy X, with normal karyotype compared with induced abortions and peripheral blood lymphocytes of adult individuals

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4. Fig. 4. Dependence of the average methylation level of the analyzed CpG sites of the PTPRN2 and PRDM16 genes in chorionic villi in the group of spontaneous abortions with normal karyotype on the average methylation level of the retrotransposon LINE‑1

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5. Fig. 5. Dependence of the average methylation level of the analyzed CpG sites of the PTPRN2 and PRDM16 genes in chorionic villi in the group of spontaneous abortions with monosomy X on the maternal age

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Copyright (c) 2023 Vasilyev S.A., Vasilyeva O.Y., Oppong-Peprah B., Demeneva V.V., Zuev A.S., Sazhenova E.A., Nikitina T.V., Tolmacheva E.N.

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