Relics of ancient viral infections are scattered throughout the genomes of many organisms, including humans. The DNA that a virus leaves behind can disrupt genes or cause cancer, but sometimes it does a body good. Take the case of the sheep's placenta: Without a gene from the endogenous Jaagsiekte sheep retrovirus (enJSRV), the organ doesn't develop properly and pregnancies fail, according to a new study. The findings indicate that such viruses may have played an important role in the evolution of the placenta.
The placenta forms when cells in the outermost layer of the embryo fuse with those lining the walls of the uterus. In many mammals, the placenta is loaded with certain viral envelope proteins, leading scientists to suspect that these proteins may be essential for its development. Indeed, experiments done with human and mouse cells in culture show that these proteins can make cells fuse with each other, suggesting that they may be responsible for the fusion of cells in the developing placenta.
To test the theory in live animals, embryologist Thomas Spencer of Texas A&M University in College Station and colleagues lowered the expression of the enJSRV envelope protein in pregnant sheep. The team injected fragments of DNA specifically designed to block the creation of the enJSRV envelope protein into sheep uteruses 8 days after fertilization--6 to 8 days before the placenta begins to form. By the 16th day after fertilization, the treated embryos were already smaller and more fragile than controls that were treated with random DNA fragments. None of the five treated embryos' placentas formed properly, and all but one died by day 20.
"This is the first study done within animals that strongly supports the idea that endogenous retroviruses have become essential for placental development and thus successful reproduction of some mammals," says Spencer, whose team reports its work online this week in the Proceedings of the National Academy of Sciences (PNAS). Because similar viruses are present in the placentas of a wide range of mammals, including humans, the placenta might have evolved multiple times during evolution with different viruses playing a role, says study author and veterinary pathologist Massimo Palmarini of the University of Glasgow Veterinary School in the U.K.
Until this study, there were only "correlations and suspicion" that viral gene products could be involved in the development of the placenta, but nothing had been proven, says R. Michael Roberts, a developmental biologist at the University of Missouri, Columbia. Spencer hopes that future studies will reveal exactly how the envelope protein regulates the growth and development of the placenta.