Russian Journal of GeneticsRussian Journal of GeneticsГенетика0016-67583034-5103The Russian Academy of Sciences66720910.31857/S0016675824080015bgelptОБЗОРНЫЕ И ТЕОРЕТИЧЕСКИЕ СТАТЬИReview ArticleGenome-Wide Analysis in the Study of the Fetal Growth Restriction PathogeneticsПолногеномный анализ в изучении патогенетики задержки роста плодаGavrilenkoM. M.ГавриленкоМ. М.
Russian Federation
maria.gavrilenko@medgenetics.ruTrifonovaE. A.ТрифоноваЕ. А.
Russian Federation
maria.gavrilenko@medgenetics.ruStepanovV. A.СтепановВ. А.
Russian Federation
maria.gavrilenko@medgenetics.ruResearch Institute of Medical Genetics, Tomsk National Research Medical CenterНаучно-исследовательский институт медицинской генетики Томского национального исследовательского медицинского центра Российской академии наук1508202460831726022025Copyright ©; 2024, Russian Academy of SciencesCopyright ©; 2024, Российская академия наук2024Russian Academy of SciencesРоссийская академия наукhttps://transsyst.ru/0016-6758/article/view/667209

Fetal growth restriction is a complication of pregnancy that defined as the inability of the fetus to realize its genetically determined growth potential. Despite the high social and medical significance of this problem the exact pathogenesis of fetal growth restriction is not known by now. Therefore, the analysis of the molecular genetics mechanisms of this pathology within the framework of approaches using modern high-performance technologies of next generation sequencing is of undoubted interest. In this review we focused on the analysis of data obtained in studies of the fetal growth restriction genetics component. The authors of these researches used next generation sequencing technologies and carried out whole transcriptome profiling. The results of the genes expression genome-wide analysis in placental tissue allow us to identify 1430 differentially expressed genes between fetal growth restriction and normal pregnancy, of which only 1% were found in at least two studies. These differentially expressed genes are involved in the Wnt/β-catenin signaling pathway that plays an important role in cell migration, neural pattern formation and organogenesis during embryonic development. Common genes are associated with both obstetric and gynecological diseases, as well as with various somatic conditions from the groups of neurodegenerative, cardiovascular diseases and mental disorders, which probably reflects their involvement in the development of postnatal consequences of fetal growth restriction. The results of our work don‘t point only to potential molecular mechanisms and key genes underlying fetal growth restriction, but also indicate the important role of gene-gene communications in this pathology implementation: about 30% of all identified differentially expressed genes products interact with each other within the same gene network. In general, genome-wide RNA sequencing combined with the analysis of protein-protein interactions represents a promising direction in research on the development and functioning of the placenta, as well as the identification of placental insufficiency diseases genetics mechanisms, including fetal growth restriction.

Задержка роста плода – осложнение беременности, определяемое как неспособность плода реализовать свой генетически обусловленный потенциал роста. Несмотря на высокую социальную и медицинскую значимость этой проблемы, к настоящему времени точный патогенез задержки роста плода не известен, поэтому несомненный интерес представляет анализ молекулярно-генетических механизмов данной патологии в рамках подходов, использующих современные высокопроизводительные технологии массового параллельного секвенирования. В настоящем обзоре мы сконцентрировались на анализе данных, полученных в исследованиях генетической компоненты задержки роста плода, авторами которых использованы технологии массового параллельного секвенирования и осуществлено полнотранскриптомное профилирование. Результаты полногеномного анализа экспрессии генов плацентарной ткани позволяют выделить 1430 дифференциально экспрессирующихся при задержке роста плода и физиологической беременности генов, из которых только 1% найден хотя бы в двух работах. Эти дифференциально экспрессирующиеся гены вовлечены в сигнальный путь Wnt/β-катенина, который играет важную роль в миграции клеток, формировании нейронных паттернов и органогенезе во время эмбрионального развития. Общие гены ассоциированы как с акушерскими и гинекологическими заболеваниями, так и с различными соматическими состояниями из групп нейродегенеративных, сердечно-сосудистых заболеваний, психических расстройств, что, вероятно, отражает их вовлеченность в развитие постнатальных последствий задержки роста плода. Результаты нашей работы не только указывают на потенциальные молекулярные механизмы и ключевые гены, лежащие в основе задержки роста плода, но также свидетельствует о важной роли ген-генных коммуникаций в механизмах реализации этой патологии: около 30% продуктов всех идентифицированных дифференциально экспрессирующихся генов взаимодействуют между собой в рамках одной генной сети. В целом, полногеномное секвенирование РНК в совокупности с анализом белок-белковых взаимосвязей, представляет собой перспективное направление в исследованиях развития и функционирования плаценты, а также идентификации молекулярно-генетических механизмов заболеваний, связанных с плацентарной недостаточностью, в том числе с задержкой роста плода.

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