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

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.

Automated summary

The study assessed the methylation level of LINE-1 retrotransposon in chorionic villi of first trimester miscarriages with normal karyotype and aneuploidy, finding significantly elevated methylation levels in aneuploid miscarriages compared to induced abortions. The methylation levels were specific for different aneuploidies, increased with gestational age, decreased with maternal age in normal karyotype miscarriages, and increased with paternal age in certain aneuploidies. The results suggest significant epigenetic changes in repetitive sequences may complement the pathogenic effects of aneuploidy in human embryogenesis.