Methylation of the Retrotransposon LINE-1 Subfamilies in Chorionic Villi of Miscarriages

Abstract

Miscarriage is potentially associated with abnormal epigenetic regulation of genes responsible for the development of the embryo and placenta. The aim of this work was to analyze the methylation level of various subfamilies of the LINE-1 retrotransposon, which makes up about 17% of the entire genome, in chorionic villi of spontaneous abortions of the first trimester of pregnancy with different karyotypes, including the most common aneuploidies. The methylation profile in the LINE-1 retrotransposon promoter was analyzed using targeted bisulfite massive parallel sequencing in chorionic villi of induced abortions (n = 39), spontaneous abortions with normal karyotype (n = 173), trisomy 16 (n = 62) and monosomy X (n = 46), and peripheral blood lymphocytes of healthy volunteers (n = 17). The level of methylation of the LINE-1 retrotransposon subfamilies in the control groups of adult lymphocytes and chorionic villi of induced abortions was the highest for evolutionarily young L1HS subfamilies, lower for the more ancient L1PA2 and L1PA3 subfamilies, and the lowest for the even more ancient L1PA4 subfamily. In the groups of spontaneous abortions, an increased level of LINE-1 methylation was observed, and this effect was more pronounced for the older LINE-1 subfamilies. The revealed patterns indicate less control over the older subfamilies of the LINE-1 retrotransposon in the human genome, which can potentially be used as regulatory elements for nearby genes involved in embryonic development. An increase in the level of methylation of such sequences can disrupt the development of the placenta and embryo and make a certain contribution to miscarriage.