Impact of viral particles and viral proteins at the embryo-maternal interface

Human reproduction is remarkably inefficient. It is estimated that around 60% of conceptions fail during the peri-implantation stages. Although this phenomenon is largely driven by chromosomal abnormalities, we still lack a comprehensive understanding of the processes occurring at these developmental stages.

Retroviral proteins such as Syncytin-1 have been evolutionarily instrumental for placentation, and some endogenous retroviruses (ERVs) active during human embryogenesis also encode viral proteins that remain uncharacterized in this context. Remarkably, in the case of the HERVK family of ERVs, these viral proteins often assemble into viral-like particles (VLPs), which have been detected in human embryos. Although these VLPs are non-infectious, studies in cancer, aging, and neurodegeneration indicate that the presence of HERVK VLPs correlates with poorer prognoses and cellular senescence through innate immune activation and cell-to-cell communication. Conversely, endogenous retroviral proteins have also been reported to exert immunoprotective functions in the embryo, suggesting that the protein products of ERVs play critical roles in early human development. What is the function of VLPs and retroviral proteins in human peri-implantation? Are they involved in the interactions between the embryo and the viral and non-viral insults found in the uterine environment? To investigate this question, our lab takes advantage of chemical screenings and genome editing combined with models of the embryo – maternal interface which mimic the human blastocyst implantation into the uterus.  

In this research line, we aim to resolve the role of retroviral proteins in peri-implantation, thus contributing to bridging a crucial gap in our understanding of human reproduction, with implications for developmental biology, fertility, and pathology.