Transposable elements as key regulators of placental development

   Transposable elements (TEs), comprising over one-third of the human genome, play a crucial role in its evolution, serving as a significant source of regulatory sequences. Under normal circumstances, their activity is tightly controlled by DNA methylation mechanisms; however, the effectiveness of this suppression varies substantially across tissues. The placenta, characterized by global hypomethylation, represents a unique environment where retroviruses and retrotransposons, typically silenced in somatic cells, gain the opportunity for activation. This distinct epigenetic landscape of the placenta allows transposons to participate in the regulation of genomic activity, influencing processes ranging from early embryogenesis to postnatal development. DNA hypomethylation in the placenta not only promotes TE mobilization, but also opens the possibility of using their components as independent genes and regulatory elements – promoters, enhancers, and other functional modules. These elements are involved in key aspects of placental development, including syncytiotrophoblast formation, extravillous trophoblast invasion, spiral artery remodeling, and endometrial decidualization. Importantly, TEs can serve as sources of alternative promoters for neighboring genes, and ancient mammalian transposons contain multiple transcription factor binding sites, enabling coordinated regulation of genes sharing a common function. Despite the growing interest in the role of transposable elements in placental development and function, many questions remain unanswered. In particular, the mechanisms of non-long terminal repeat (non-LTR) retrotransposon function during pregnancy remain poorly understood. A deep understanding of these processes is necessary to elucidate regulatory disorders in the placenta associated with major obstetric syndromes. This review examines the contribution of transposable elements to the functioning of the human genome, particularly their impact on gene expression, in the context of pregnancy and placental development.

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