TY - JOUR

T1 - Глобальные эпигенетические изменения в компартментах бластоцист человека при генетическом дисбалансе

AU - Tikhonov, A.V.

AU - Krapivin, M.I.

AU - Malysheva, O.V.

AU - Koltsova, A.S.

AU - Komarova, E.M.

AU - Golubeva, A.V.

AU - Efimova, O.A.

AU - Pendina, A.A.

N1 - Export Date: 21 October 2024 Адрес для корреспонденции: Tikhonov, A.V.2 Men-deleyevskaya line, Russian Federation; эл. почта: tixonov5790@gmail.com

PY - 2024/9/29

Y1 - 2024/9/29

N2 - BACKGROUND: Epigenetic genome reprogramming is an important determinant of human embryo development. However, its mechanisms remain poorly elucidated, especially in genetically unbalanced embryos. AIM: The aim of this study is the analysis of DNA methylation and hydroxymethylation levels in trophectoderm and inner cell mass of genetically balanced and unbalanced human blastocysts. MATERIALS AND METHODS: Twenty-two IVF-derived human blastocysts were enrolled in the study; of these blastocysts, 15 were genetically unbalanced and 7 — genetically balanced. Detection of 5-methylcytosine and 5-hydroxymethylcytosine was performed on trophectoderm and inner cell mass nuclei by indirect immunofluorescence. RESULTS: In genetically unbalanced blastocysts, the DNA methylation level was elevated in both compartments. The DNA hydroxymethylation level, in contrast, was elevated only in inner cell mass, whereas trophectoderm cells retained the same level as in genetically balanced embryos. These changes equalized the inner cell mass and trophectoderm DNA hydroxymethylation levels in genetically unbalanced blastocysts, while in genetically balanced ones the 5-hydroxymethylcytosine content in inner cell mass lagged behind that in trophectoderm. CONCLUSIONS: Genetic imbalance is associated with differential epigenetic changes in trophectoderm and inner cell mass cells of human blastocysts: DNA methylation level increases in both compartments while DNA hydroxymethylation level increases only in inner cell mass. The trophectoderm cells in genetically unbalanced blastocysts retain the same hydroxymethylation level as in genetically balanced ones, suggesting a possible explanation of the ability of karyotypically abnormal embryos to implant. All rights reserved © Eco-Vector, 2024.

AB - BACKGROUND: Epigenetic genome reprogramming is an important determinant of human embryo development. However, its mechanisms remain poorly elucidated, especially in genetically unbalanced embryos. AIM: The aim of this study is the analysis of DNA methylation and hydroxymethylation levels in trophectoderm and inner cell mass of genetically balanced and unbalanced human blastocysts. MATERIALS AND METHODS: Twenty-two IVF-derived human blastocysts were enrolled in the study; of these blastocysts, 15 were genetically unbalanced and 7 — genetically balanced. Detection of 5-methylcytosine and 5-hydroxymethylcytosine was performed on trophectoderm and inner cell mass nuclei by indirect immunofluorescence. RESULTS: In genetically unbalanced blastocysts, the DNA methylation level was elevated in both compartments. The DNA hydroxymethylation level, in contrast, was elevated only in inner cell mass, whereas trophectoderm cells retained the same level as in genetically balanced embryos. These changes equalized the inner cell mass and trophectoderm DNA hydroxymethylation levels in genetically unbalanced blastocysts, while in genetically balanced ones the 5-hydroxymethylcytosine content in inner cell mass lagged behind that in trophectoderm. CONCLUSIONS: Genetic imbalance is associated with differential epigenetic changes in trophectoderm and inner cell mass cells of human blastocysts: DNA methylation level increases in both compartments while DNA hydroxymethylation level increases only in inner cell mass. The trophectoderm cells in genetically unbalanced blastocysts retain the same hydroxymethylation level as in genetically balanced ones, suggesting a possible explanation of the ability of karyotypically abnormal embryos to implant. All rights reserved © Eco-Vector, 2024.

KW - 5-hydroxymethylcytosine

KW - 5-methylcytosine

KW - aneuploidy

KW - assisted reproductive technologies

KW - human blastocyst

KW - inner cell mass

KW - trophectoderm

KW - 5-hydroxymethylcytosine

KW - 5-methylcytosine

KW - aneuploidy

KW - assisted reproductive technologies

KW - human blastocyst

KW - inner cell mass

KW - trophectoderm

UR - https://www.mendeley.com/catalogue/f2fe654a-3323-37f6-bf03-610bf0e79dbe/

U2 - 10.17816/ecogen631776

DO - 10.17816/ecogen631776

M3 - статья

VL - 22

SP - 265

EP - 276

JO - ЭКОЛОГИЧЕСКАЯ ГЕНЕТИКА

JF - ЭКОЛОГИЧЕСКАЯ ГЕНЕТИКА

SN - 1811-0932

IS - 3

ER -