Accepted_test

DNA methylation is one of the key mechanisms responsible for the implementation of the individual development program. The purpose of this study is to identify the potential role of multiple abnormalities in the methylome of extraembryonic tissues in the death of human embryos at early stages of development.

Methods and Algorithms: The methylation level was assessed using reduced representation bisulfite sequencing (RRBS) in chorionic villi of 8 spontaneous abortions of the first trimester of pregnancy with 45,X karyotype and 7 induced abortions with normal 46,XX and 46,XY karyotypes. Using STR analysis, the parental origin of the X chromosome was established in spontaneous abortions 45,X. Also, we analyzed 8 spontaneous abortions of the first trimester of pregnancy with normal karyotype with high and low level of LINE-1 methylation using RRBS.

Moreover, we analyzed the methylation profile of the LINE-1 retrotransposon using targeted bisulfite massive parallel sequencing in pairs of spontaneous abortions from the same families (n=21 pairs).

Conclusion: Aberrant methylation of genes involved in placentation, proliferation, and cell differentiation has been found in spontaneous miscarriages with monosomy X and normal karyotype. These disorders are likely to be the cause of the embryo lethality. The detected correlation between the levels of methylation of the LINE-1 retrotransposon in the chorionic villi of spontaneous abortions from the same families may be a consequence of common maternal factors affecting embryos and associated with their death, or indirect evidence of a transgenerational effect on the level of LINE-1 methylation of at least one from parents.