vavilovВавиловский журнал генетики и селекцииVavilov Journal of Genetics and Breeding2500-3259Institute of Cytology and Genetics of Siberian Branch of the RAS10.18699/vjgb-26-69vavilov-5184Research ArticleМЕДИЦИНСКАЯ ГЕНЕТИКАMEDICAL GENETICSМобильные генетические элементы в патогенезе репродуктивных нарушений человекаMobile genetic elements in the pathogenesis of human reproductive disordershttps://orcid.org/0000-0002-1193-5579БабовскаяА. А.BabovskayaA. A.

Томск

Tomsk

anastasia.babovskaya@medgenetics.ruhttps://orcid.org/0000-0003-1311-7403ТрифоноваЕ. А.TrifonovaE. A.

Томск

Tomsk

https://orcid.org/0000-0002-5166-331XСтепановВ. А.StepanovV. A.

Томск

Tomsk

Научно-исследовательский институт медицинской генетики Томского национального исследовательского медицинского центраРоссияResearch Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of SciencesRussian Federation202624072026304685695Copyright © Бабовская А.А., Трифонова Е.А., Степанов В.А., 20262026Бабовская А.А., Трифонова Е.А., Степанов В.А.Babovskaya A.A., Trifonova E.A., Stepanov V.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://vavilov.elpub.ru/jour/article/view/5184

Мобильные генетические элементы (МГЭ), или транспозоны, представляют собой автономные последовательности ДНК, способные к перемещению и распространению в пределах генома. Долгое время рассматривавшиеся как «эгоистичная» или «мусорная» ДНК в настоящее время МГЭ считаются одними из компонентов, принимающих участие в эволюции генома, регуляции экспрессии генов и патогенезе ряда заболеваний. У человека МГЭ подразделяются на два основных класса: ретротранспозоны (I класс), реплицирующиеся через промежуточную стадию РНК по механизму «копирования–вставки» (copy-and-paste), и ДНК-транспозоны (II класс), перемещающиеся по механизму «вырезания–вставки» (cut-and-paste) без РНК-интермедиата. Ретротранспозоны, по данным проекта «Геном человека», составляют примерно 42 % от доли МГЭ в человеческом геноме. Наиболее многочисленны ретротранспозоны без длинных концевых повторов (non-LTR), среди которых доминируют автономные элементы LINE-1. Несмотря на то что в геноме присутствует около 500 000 копий LINE-1, большинство из них дефектно и лишь малая часть (<100) сохраняет возможность к транспозиции у современного человека. Второй по распространенности группой (около 10.6 %) семейства ретротранспозонов являются короткие диспергированные повторы Alu (SINE-элементы), которые, будучи неавтономными, используют для перемещения и встраивания молекулярный аппарат LINE-1. Активность МГЭ – строго регулируемый процесс в соматических тканях. Эпигенетические механизмы, в частности метилирование ДНК, в норме эффективно подавляют экспрессию и мобильность мобильных генетических элементов. Нарушение этого контроля ассоциировано с широким спектром патологий. Так, гипометилирование и реактивация ретротранспозонов, в особенности LINE-1, продемонстрированы при различных типах рака, нейродегенеративных и аутоиммунных заболеваниях. Цель настоящего обзора – систематический анализ современных представлений о роли мобильных генетических элементов, в частности ретротранспозонов LINE-1, Alu и HERV, в развитии заболеваний репродуктивной системы человека, также включая заболевания, связанные с патологией плаценты, область которых остается недостаточно изученной, несмотря на растущий объем данных.

Mobile genetic elements (MGEs), or transposons, are autonomous DNA sequences capable of moving and proliferating within the genome. Long considered “selfish” or “junk” DNA, MGEs are now recognized as key components involved in genome evolution, the regulation of gene expression, and the pathogenesis of various diseases. In humans, MGEs are divided into two main classes: retrotransposons (Class I), which replicate via an RNA intermediate through a “copy-and-paste” mechanism, and DNA transposons (Class II), which move via a “cut-and-paste” mechanism without an RNA intermediate. According to the Human Genome Project, retrotransposons constitute the majority (approximately 42 %) of the MGE fraction within the human genome. The most abundant are the non-long terminal repeat (non-LTR) retrotransposons, dominated by autonomous LINE-1 elements. Although approximately 500,000 LINE-1 copies are present in the genome, the vast majority are defective, and only a small fraction (<100) retain the capacity for transposition in modern humans. The second most prevalent group (about 10.6 %) within the retrotransposon family is the short interspersed nuclear elements (SINEs), specifically Alu elements, which are non-autonomous and hijack the LINE-1 molecular machinery for their mobilization and integration. MGE activity is a tightly regulated process in somatic tissues. Epigenetic mechanisms, particularly DNA methylation, normally effectively suppress MGE expression and mobility. Disruption of this control is associated with a wide range of pathologies. For instance, hypomethylation and reactivation of retrotransposons, notably LINE-1, have been demonstrated in various cancers, as well as in neurodegenerative and autoimmune diseases. The aim of this review is to provide a systematic analysis of the current understanding of the role of mobile genetic elements, particularly LINE-1, Alu, and HERV retrotransposons, in the development of human reproductive system disorders. This also includes diseases associated with placental pathology, an area that remains insufficiently studied to date, despite a growing body of data.

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