syncytins

Syncytins are fusogenic envelope proteins encoded by endogenous retroviral genes that have been domesticated by mammalian genomes for use in placental development. In humans, the best characterized examples are Syncytin-1, encoded by the HERV-W–derived ERVWE1, and Syncytin-2, encoded by the HERV-FRD–derived ERVFRD-1. Across mammals, multiple other syncytin genes have been identified, each arising from a different ancestral retrovirus.

These proteins mediate cell fusion between trophoblasts to form the syncytiotrophoblast, a multinucleated layer that lines placental villi and facilitates nutrient transfer and barrier functions between mother and fetus. Expression of syncytins is largely placental-restricted and tightly regulated by host transcription factors and epigenetic mechanisms. The fusogenic activity is intrinsic to the envelope proteins, and some studies also suggest immunomodulatory properties that may contribute to maternal immune tolerance at the interface.

The existence of syncytins is often cited as an example of exaptation, where viral genetic material has been repurposed for a physiological function. In humans, abnormal syncytin expression has been associated with placental pathologies such as preeclampsia and fetal growth restriction, though causal relationships remain under investigation. The diversity of syncytin genes across species underscores the convergent evolution of this placental fusion mechanism.