Mobile genetic elements in the pathogenesis of human reproductive disorders

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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