1. LINE-1 retrotransposon methylation in chorionic villi of first trimester miscarriages with aneuploidy
- Author
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D. I. Zhigalina, Vasilissa A Lee, T. V. Nikitina, S. A. Vasilyev, Oksana Yu Vasilyeva, E. A. Sazhenova, I. N. Lebedev, E. N. Tolmacheva, Lada A. Zatula, Ekaterina S Serdyukova, A. A. Kashevarova, and Anton V. Markov
- Subjects
0301 basic medicine ,Adult ,Aneuploidy ,Embryonic Development ,Biology ,Miscarriage ,Andrology ,03 medical and health sciences ,0302 clinical medicine ,Pregnancy ,Genetics ,medicine ,Humans ,Genetics (clinical) ,030219 obstetrics & reproductive medicine ,метилирование ДНК ,анеуплоидия ,Obstetrics and Gynecology ,Trisomy 16 ,Karyotype ,General Medicine ,Methylation ,DNA Methylation ,medicine.disease ,Abortion, Spontaneous ,Pregnancy Trimester, First ,030104 developmental biology ,medicine.anatomical_structure ,Long Interspersed Nucleotide Elements ,Reproductive Physiology and Disease ,Reproductive Medicine ,ретротранспозоны ,DNA methylation ,Chorionic villi ,Female ,Chorionic Villi ,Trisomy ,Developmental Biology - 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.
- Published
- 2020