Transposable elements (TEs) are mobile DNA sequences that have extensively colonized mammalian genomes, representing up to half of the DNA content. Far from being passive passengers, they are powerful agents of change: over evolutionary timescales, TEs have been repeatedly co-opted to fuel innovation and adaptation. Yet in the short term, they pose a constant threat, as uncontrolled activity undermines genome integrity and cellular function. Indeed, unrestrained TE reactivation is linked to a wide spectrum of pathological states—including infertility, ageing, cancer, and neurological disorders—through both transposition-dependent and -independent mechanisms. Understanding the interplay between host genomes and their TE residents is therefore a central question with profound implications for development, evolution, and disease. Our research focuses on the multilayered surveillance strategies deployed by mammalian cells to restrain—and occasionally domesticate—TEs, and their regulation and requirements in reproduction.
Indeed, reproductive cells represent a critical battlefield for this host–TE interplay. For TEs, germ cells are the gateway to immortality: only insertions in this lineage ensure vertical inheritance and propagation. For the host, however, unchecked germline TE activity is catastrophic, introducing heritable mutations that can compromise reproduction and species fitness. Paradoxically, mammalian germline development involves a programmed phase of epigenetic reprogramming during which DNA methylation—the primary defense against TEs—is erased genome-wide. This transient relaxation permits TE transcription, yet genomic invasion does not occur. If, however, this permissive window extends beyond its natural boundaries, meiosis is compromised, leading to germ cell collapse and infertility.
The HOTIMAGE project seeks to unravel the molecular mechanisms that integrate TEs into the mammalian germline program and to assess their impact on fertility, using the mouse as a model. We aim to elucidate how TEs are distinguished from genes and how the successive phases of spermatogenesis are protected from their deleterious effects. Ultimately, this work will provide a new conceptual framework for the role of TEs in shaping male gamete production, with far-reaching implications for the etiology of fertility disorders.
