Fragments of ancient viral DNA, known as human endogenous retroviruses (HERVs), play a critical role in the initial stages of human embryonic development. These remnants, which constitute approximately 8.9% of the human genome, are not merely fossilized genetic material but are actively involved in the fundamental processes of life's beginning. Research also showed that these ancient viral sequences, previously considered "junk" DNA, are activated shortly after fertilization in various mammals, including mice, cows, pigs, rabbits, and rhesus macaques.
Groundbreaking research published in the journal Nature highlights the essential regulatory function of these viral elements. The study, led by Dr. Raquel Fueyo from Stanford University, focused on a specific type of HERV called LTR5Hs. Using advanced three-dimensional stem cell models, known as blastoids, scientists observed that inhibiting these viral elements disrupted the proper formation of the blastoids. Conversely, moderate inhibition allowed for partial development, indicating that LTR5Hs act as vital enhancers, orchestrating the activity of genes necessary for the development of the epiblast, the layer that eventually forms the embryo itself.
One unique LTR5Hs element in humans has been identified as enhancing the expression of the ZNF729 gene, which is fundamental for basic cellular functions such as proliferation and metabolism. The absence of this viral element prevented the generation of blastoids, underscoring its critical importance. The research, conducted in Professor Joanna Wysocka's lab at Stanford University, suggests that these ancient viral mechanisms may also influence other areas beyond early embryogenesis, including tissue formation, the development of diseases, and human fertility.
The findings have significant implications for understanding reproductive disorders and exploring genetic variations in these viral elements across different populations. This discovery not only reshapes our understanding of human embryogenesis but also opens new avenues for therapeutic interventions, potentially targeting these ancient viral sequences for the treatment of various diseases.