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

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. 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.

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

“…The presence of significant correlations between increased methylation of individual gene promoters and genome hypermethylation, and the fact that the LINE-1 retrotransposon methylation index is increased in the chorionic villi of miscarriages with trisomy 16 compared to induced abortions 15 , indicate that the hypermethylation of DNA in trisomy 16 may be specific to the whole genome. This process is likely triggered by specific gene(s) that are located on chromosome 16.…”

“…When the conventional cytogenetic analysis was noninformative, karyotypes were assessed using chromosomal comparative genome hybridization (cCGH, n = 6) or array comparative genome hybridization (aCGH, n = 4) (Fig. 1 ) as described elsewhere 15 .…”

Relationship between degree of methylation of sperm long interspersed nuclear element-1 (LINE-1) gene and alteration of sperm parameters and age: a meta-regression analysis

“…Finally, it has recently been shown that age-related paternal hypermethylation of LINE1 can be transmitted to offspring. Indeed, a study of 141 chorionic villus samples from trisomic or with monosomy X abortions showed an increase in LINE1 methylation as paternal age increased, suggesting that LINE1 methylation may be inherited and that aging causes an increase in sperm LINE1 methylation [ 44 ].…”

DNA Hypermethylation and a Specific Methylation Spectrum on the X Chromosome in Turner Syndrome as Determined by Nanopore Sequencing

“…Previous studies indicated that the insertion of mobile elements into the early embryo can disrupt genes, leading to diseases [ 23 , 24 ]. Therefore, it would be interesting to consider the methylation features of TEs in the villi during early spontaneous abortions [ 25 , 26 ]. We speculate that the regulation of methylation may be a self-rescue process for live TS fetuses in order to maintain the stability of the genome and their survival.…”