Cytogenetic mechanisms of aneuploidy in somatic cells of chemonuclear industry professionals with incorporated plutonium-239

Vasilyev, S. A.; Timoshevsky, V. A.; Lebedev, I. N.

doi:10.1134/s1022795410110141

Cited by 8 publications

(3 citation statements)

References 20 publications

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“…DNA probes were kindly provided by Prof. Mariano Rocchi at the University of Bari, Italy. FISH was performed as previously described 32 . Thirteen miscarriages had mosaicism of trisomy 16 (aneuploid clone—from 10 to 89%), and 16 miscarriages had pure trisomy 16 (aneuploid clone ≥ 90%).…”

Section: Methodsmentioning

confidence: 99%

Identification of differentially methylated genes in first-trimester placentas with trisomy 16

Tolmacheva

Vasilyev

Nikitina

et al. 2022

Sci Rep

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The presence of an extra chromosome in the embryo karyotype often dramatically affects the fate of pregnancy. Trisomy 16 is the most common aneuploidy in first-trimester miscarriages. The present study identified changes in DNA methylation in chorionic villi of miscarriages with trisomy 16. Ninety-seven differentially methylated sites in 91 genes were identified (false discovery rate (FDR) < 0.05 and Δβ > 0.15) using DNA methylation arrays. Most of the differentially methylated genes encoded secreted proteins, signaling peptides, and receptors with disulfide bonds. Subsequent analysis using targeted bisulfite massive parallel sequencing showed hypermethylation of the promoters of specific genes in miscarriages with trisomy 16 but not miscarriages with other aneuploidies. Some of the genes were responsible for the development of the placenta and embryo (GATA3-AS1, TRPV6, SCL13A4, and CALCB) and the formation of the mitotic spindle (ANKRD53). Hypermethylation of GATA3-AS1 was associated with reduced expression of GATA3 protein in chorionic villi of miscarriages with trisomy 16. Aberrant hypermethylation of genes may lead to a decrease in expression, impaired trophoblast differentiation and invasion, mitotic disorders, chromosomal mosaicism and karyotype self-correction via trisomy rescue mechanisms.

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Section: Methodsmentioning

confidence: 99%

Identification of differentially methylated genes in first-trimester placentas with trisomy 16

Tolmacheva

Vasilyev

Nikitina

et al. 2022

Sci Rep

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“…Centromere-specific DNA probes for X chromosomes were used for the analysis of monosomy X and subtelomeric DNA probes (16q and 16p) were used for the analysis of tri so my 16. The analysis was carried out according to the protocol described elsewhere (Vasilyev et al, 2010). Four samples had a mosaic karyotype with a trisomy level from 10 to 90 %.…”

Section: Methodsmentioning

confidence: 99%

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

et al. 2023

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The placenta has a unique hypomethylated genome. Due to this feature of the placenta, there is a potential possibility of using regulatory elements derived from retroviruses and retrotransposons, which are suppressed by DNA methylation in the adult body. In addition, there is an abnormal increase in the level of methylation of the LINE-1 retrotransposon in the chorionic trophoblast in spontaneous abortions with both normal karyotype and aneuploidy on different chromosomes, which may be associated with impaired gene transcription using LINE-1 regulatory elements. To date, 988 genes that can be expressed from alternative LINE-1 promoters have been identified. Using the STRING tool, genes (NUP153 and YWHAB) were selected, the products of which have significant functional relationships with proteins highly expressed in the placenta and involved in trophoblast differentiation. This study aimed to analyze the expression of the NUP153 and YWHAB genes, highly active in the placenta, from canonical and alternative LINE-1 promoters in the germinal part of the placenta of spontaneous and induced abortions. Gene expression analysis was performed using real-time PCR in chorionic villi and extraembryonic mesoderm of induced abortions (n = 10), adult lymphocytes (n = 10), spontaneous abortions with normal karyotype (n = 10), and with the most frequent aneuploidies in the first trimester of pregnancy (trisomy 16 (n = 8) and monosomy X (n = 6)). The LINE-1 methylation index was assessed in the chorionic villi of spontaneous abortions using targeted bisulfite massive parallel sequencing. The level of expression of both genes from canonical promoters was higher in blood lymphocytes than in placental tissues (p < 0.05). However, the expression level of the NUP153 gene from the alternative LINE-1 promoter was 17 times higher in chorionic villi and 23 times higher in extraembryonic mesoderm than in lymphocytes (p < 0.05). The expression level of NUP153 and YWHAB from canonical promoters was higher in the group of spontaneous abortions with monosomy X compared to all other groups (p < 0.05). The LINE-1 methylation index negatively correlated with the level of gene expression from both canonical (NUP153 – R = –0.59, YWHAB – R = –0.52, p < 0.05) and alternative LINE-1 promoters (NUP153 – R = –0.46, YWHAB – R = –0.66, p < 0.05). Thus, the observed increase in the LINE-1 methylation index in the placenta of spontaneous abortions is associated with the level of expression of the NUP153 and YWHAB genes not only from alternative but also from canonical promoters, which can subsequently lead to negative consequences for normal embryogenesis.

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“…All DNA probes were kindly provided by Prof. Mariano Rocchi at the University of Bari. FISH was performed as previously described [32].…”

Section: Fishmentioning

confidence: 99%

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

Vasilyev

Tolmacheva

Vasilyeva

et al. 2020

J Assist Reprod Genet

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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. ResultsThe 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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Cytogenetic mechanisms of aneuploidy in somatic cells of chemonuclear industry professionals with incorporated plutonium-239

Cited by 8 publications

References 20 publications

Identification of differentially methylated genes in first-trimester placentas with trisomy 16

Identification of differentially methylated genes in first-trimester placentas with trisomy 16

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

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

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