The important biological roles of Syncytin-1 of human endogenous retrovirus W (HERV-W) and Syncytin-2 of HERV-FRD in the human placenta development

Background: Human endogenous retroviruses (HERVs) entered the germ line by retroviral infection from a distant ancestor over 30 million years ago and constitute 8% of the human genome. The majorities of HERVs are non-protein coding and lack function because of the accumulation of mutations, insertions, deletions, and/or truncations. However, a small number of HERV genes carried ORFs with beneficial functions for the host. Methods & results: In this review, we summarize the structural and important biological roles of two HERV gene products termed Syncytin-1 and Syncytin-2 in human placenta development. Indeed, two retroviral gene products that have important roles in mammalian development, Syncytin-1 (HERV-W) and Syncytin-2 (HERV-FRD), are prime examples encoded by env genes and expressed in the placental trophoblasts. Several pivotal studies revealed that Syncytins are fundamental genes implicated in regulating trophoblast fusion and placenta morphogenesis. Conclusion: Interestingly, it has been suggested that syncytins may also be implicated in non-fusogenic activities leading to apoptosis, proliferation, and immunosuppressive activities.