The captured retroviral envelope syncytin-A and syncytin-B genes are conserved in the Spalacidae together with hemotrichorial placentation

Syncytins are fusogenic envelope (env) genes of retroviral origin that have been captured for a function in placentation. Multiple independent events of syncytin gene capture were found to have occurred in primates, rodents, lagomorphs, carnivores, and ruminants. In the mouse, two syncytin-A and -B genes are present, which trigger the formation of the two-layered placental syncytiotrophoblast at the maternal-fetal interface, a structure classified as hemotrichorial. Here, we identified syncytin-A and -B orthologous genes in the genome of all Muroidea species analyzed, thus dating their capture back to about at least 40 million years ago, with evidence that they evolved under strong purifying selection. We further show, in the divergent Spalacidae lineage (blind mole rats [Spalax]), that both syncytins have conserved placenta-specific expression, as revealed by RT-PCR analysis of a panel of Spalax galili tissues, and display fusogenic activity, using ex vivo cell-cell fusion assays. Refined analysis of the placental architecture and ultrastructure revealed that the Spalax placenta displays a hemotrichorial organization of the interhemal membranes, as similarly observed for other Muroidea species, yet with only one trophoblastic cell layer being clearly syncytialized. In situ hybridization experiments further localized syncytin transcripts at the level of these differentiated interhemal membranes. These findings argue for a role of syncytin gene capture in the establishment of the original hemotrichorial placenta of Muroidea, and more generally in the diversity of placental structures among mammals.