If preimplantation XCI in mice fails for any reason, it results in cell and embryo death.
Due to the difficulties of investigating XCI in human embryos (because of the shortage of embryos available for research), no one knew how XCI worked in humans and, in fact, it was thought that this initial inactivation of the X chromosome before implantation did not happen at all, and that only the random XCI after implantation occurred.
However, Ms van den Berg and her colleagues have now found the first evidence that XCI does occur in pre-implantation embryos, indicating that this mechanism of compensating for gene dosages has remained basically unchanged throughout evolution and is probably the same in all mammals that have their young attached to a placenta in the womb from mice to humans.
The researchers looked at human embryos that had been donated for scientific research by couples undergoing fertility treatment. They studied them at three stages of their development: after the embryo had divided into eight cells, the morula stage (a solid cluster of approximately 16 cells) and the blastocyst stage (about five days after fertilisation when the embryo's cells have started to differentiate into different cell layers).
They used probes designed for detecting a gene called XIST (X chromosome Inactive Specific Transcript), which is only expressed on an inactive X chromosome and is transcribed (or copied) into RNA. Other probes were used to detect the sex and chromosomal status of each embryo.
Ms van den Berg found that while the male embryos showed hardly any signs of XIST, the female embryos started to show signs of XIST at the eight-cell stage, and the XIST signal grew stronger at the morula and blastocyst stages.
"Our results are the first to show that, contrary to what was previously published, human embryos do inactivate a single
|Contact: Mary Rice|
European Society for Human Reproduction and Embryology