vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/vjgb-24-24vavilov-4090Research ArticleБИОТЕХНОЛОГИЯ В ПОСТГЕНОМНУЮ ЭРУMEDICAL GENETICSАберрантное метилирование генов развития плаценты в ворсинах хориона спонтанных абортусов с трисомией 16Aberrant methylation of placental development genes in chorionic villi of spontaneous abortions with trisomy 16ВасильеваО. Ю.VasilyevaО. Yu.

Томск

Tomsk

   

oksana.vasilyeva@medgenetics.ruТолмачеваЕ. Н.TolmachevaE. N.

Томск

Tomsk

ДмитриевА. Э.DmitrievA. E.

Томск

Tomsk

ДарковаЯ. А.DarkovaYa. A.

Томск

Tomsk

СаженоваЕ. А.SazhenovaE. A.

Томск

Tomsk

НикитинаТ. Н.NikitinaT. V.

Томск

Tomsk

ЛебедевИ. Н.LebedevI. N.

Томск

Tomsk

ВасильевС. А.VasilyevS. A.

Томск

Tomsk

Научно-исследовательский институт медицинской генетики Томского национального исследовательского медицинского центра Российской академии наукРоссияResearch Institute of Medical Genetics of the Tomsk National Research Medical Center of the Russian Academy of SciencesRussian FederationНациональный исследовательский Томский государственный университетРоссияNational Research Tomsk State UniversityRussian Federation202411042024282198203Copyright © Васильева О.Ю., Толмачева Е.Н., Дмитриев А.Э., Даркова Я.А., Саженова Е.А., Никитина Т.Н., Лебедев И.Н., Васильев С.А., 20242024Васильева О.Ю., Толмачева Е.Н., Дмитриев А.Э., Даркова Я.А., Саженова Е.А., Никитина Т.Н., Лебедев И.Н., Васильев С.А.Vasilyeva О.Y., Tolmacheva E.N., Dmitriev A.E., Darkova Y.A., Sazhenova E.A., Nikitina T.V., Lebedev I.N., Vasilyev S.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/4090

У человека анеуплоидия не совместима с рождением здоровых детей и в основном приводит к гибели эмбрионов на ранних стадиях развития в первом триместре беременности. Наиболее частая анеуплоидия среди спонтанных абортусов первого триместра беременности – трисомия 16. Однако механизмы, приводящие к гибели эмбрионов с трисомией 16, остаются недостаточно исследованными. Одним из таких потенциальных механизмов является нарушение развития плаценты, в том числе ремоделирования спиральных артерий. Ремоделирование спиральных артерий заключается в миграции клеток трофобласта в спиральные артерии матери и замещении их эндотелия для обеспечения стабильного питания эмбриона и снабжения кислородом. Это комплексный процесс, зависящий от множества факторов как со стороны эмбриона, так и со стороны матери. Нами проведен анализ уровня метилирования семи генов (ADORA2B, NPR3, PRDM1, PSG2, PHTLH, SV2C и TICAM2), участвующих в развитии плаценты, в ворсинах хориона спонтанных абортусов с трисомией 16 (n = 14), по сравнению со спонтанными абортусами с нормальным кариотипом (n = 31) и контрольной группой медицинских абортусов (n = 10). Для получения библ иотек для секвенирования использована таргетная амплификация отдельных регионов генов с помощью разработанных олигонуклеотидных праймеров на бисульфит-конвертированной ДНК. Анализ проводили с применением таргетного бисульфитного массового параллельного секвенирования. В группе спонтанных абортусов с трисомией 16 был значимо повышен уровень метилирования генов PRDM1 и PSG2 по сравнению с медицинскими абортусами (p = 0.0004 и p = 0.0015 соответственно). В группе спонтанных абортусов с нормальным кариотипом не обнаружено повышения уровня метилирования генов PRDM1 и PSG2, но был значимо повышен уровень метилирования гена ADORA2B по сравнению с медицинскими абортусами (p = 0.032). Полученные результаты указывают на потенциальные механизмы патогенетического действия трисомии 16 на развитие плаценты с участием изученных генов.

In humans, aneuploidy is incompatible with the birth of healthy children and mainly leads to the death of embryos in the early stages of development in the first trimester of pregnancy. Trisomy 16 is the most common aneup loidy among spontaneous abortions of the first trimester of pregnancy. However, the mechanisms leading to the death of embryos with trisomy 16 remain insufficiently investigated. One of these potential mechanisms is abnormal placental development, including aberrant remodeling of spiral arteries. Spiral artery remodeling involves the migration of trophoblast cells into the maternal spiral arteries, replacing their endothelium and remodeling to ensure a stable embryonic nutrition and oxygen supply. This is a complex process which depends on many factors from both the embryo and the mother. We analyzed the methylation level of seven genes (ADORA2B, NPR3, PRDM1, PSG2, PHTLH, SV2C, and TICAM2) involved in placental development in the chorionic villi of spontaneous abortions with trisomy 16 (n = 14), compared with spontaneous abortions with a normal karyotype (n = 31) and the control group of induced abortions (n = 10). To obtain sequencing libraries, targeted amplification of individual gene regions using designed oligonucleot ide primers for bisulfite-converted DNA was used. The analysis was carried out using targeted bisulfite massive parallel sequencing. In the group of spontaneous abortions with trisomy 16, the level of methylation of the PRDM1 and PSG2 genes was significantly increased compared to induced abortions (p = 0.0004 and p = 0.0015, respectively). In the group of spontaneous abortions, there was no increase in the level of methylation of the PRDM1 and PSG2 genes, but the level of methylation of the ADORA2B gene was significantly increased compared to the induced abortions (p = 0.032). The results obtained indicate the potential mechanisms of the pathogenetic effect of trisomy 16 on the placental development with the participation of the studied  genes.

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The authors declare that there are no conflicts of interest present.