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Blastocyst. The mammalian embryo is a hollow sphere, the circumference of which is formed by the cells of the trophoblast. They will participate in the formation of the placenta. The cells that will organize the embryo constitute a modest cell mass, shaped like a “button” © Medical Graphics, CC BY-NC-ND
The embryonic button will make up all of the organs of the embryo, while the peripheral trophoblast cells will be responsible for building extraembryonic structures like the placenta. Part of the trophoblast, called a syncytiotrophoblast, forms a layer of fused cells. When several cells merge, a giant cell is formed. Possessing several nuclei, this structure is called syncytium. These fused cells “attack” the maternal tissues, puncture them and allow anchoring (called implantation) of the embryo.
The fusion of trophoblast cells is an essential step for the implantation of the embryo in the uterus and for the proper course of development. It is provided by specific proteins: syncytins. Syncytin-like proteins are expressed in the placentas of almost all mammals. The simultaneous loss of the two types of syncytins expressed in mice prevents the development of a placenta and causes the early death of embryos, emphasizing their crucial role in development.
Retroviral nudges: exhilarating exaptation
The viral origin of syncytines has been demonstrated by paleovirologists, who are able to detect in a genome “fossil viruses” or sequences resulting from the integration, in the past, of viral genetic material. This viral origin provides an amazing example of the phenomenon called exaptation.
By the term exaptation, Stephen J. Gould and Elizabeth Vrba illustrated how complex functions can arise from simple structures or elements. For example, selected because they ensured temperature regulation, the feathers would then have allowed adaptation to flight.
The genes called Env , which belong to a family of genes encoding proteins forming the viral envelope, provide another example of exaptation. At the retrovirus , the proteins Env , encoded by these genes, are envelope proteins by which viral particles fuse their membranes with those of target cells. This fusion allows infection of the cell by bypassing the host’s immune system. Integrated and transmitted to progeny in mammals, these Env genes have evolved into syncytin-like proteins.
Is the appearance of the placenta a unique event?
It is astonishing to note that the domestication of these genes was not done only once, but derives from at least ten independent infections by different retroviruses, during the evolution of mammals. The acquisition of a placenta would therefore be a convergent development. The oldest known type of syncytin has been identified in carnivores. Integration of the conserved syncytin-1 gene in humans is believed to have occurred 30 million years ago, while syncytin genes integrated in mice more than 25 million years ago.
Different retroviral infections have therefore repeatedly favored cell fusion mechanisms leading to the formation of syncytium at the interface between fetal and maternal tissues and contributing to the development of original intrauterine development, thanks to the formation of a “retroviral envelope”. The cell fusion and immunosuppressive properties of syncytins would have favored the maintenance and development of this new structure.