Epigenetic reprogramming aids development of human gametes in vitro

For the first time, human stem cells that were originally skin cells have been reprogrammed into early-stage sperm and egg precursors.

Published in Nature, by a team of Japanese researchers at Kyoto University, the study describes the method used to produce large quantities of early-stage sperm and egg cells from stem cells by erasing the epigenetic 'memory' that determines which genes are expressed. In future this could help people who are infertile or in same-sex couples to have a biologically-related child.

'Epigenetic reprogramming is key to making the next generation,' said developmental biologist Professor Mitinori Saitou from the Institute for the Advanced Study of Human Biology who led this research.

The team set out to bridge the gap between previous research which was able to grow mouse eggs using stem-cell-like cells generated from skin (see BioNews 1231). Crucial to the team's success was discovering that the addition of a protein called bone morphogenetic protein (BMP2) was essential to promote epigenetic reprogramming. The cells advanced one step further in their development compared to cells in cultures without added BMP2.

'The results of this research are an important milestone in clarifying the mechanism of human germ cell development and the promotion of research on the in vitro development of human germ cells,' the researchers said.

After this epigenetic reprogramming, the cells' development stopped and Professor Saitou acknowledged that there are still further steps to be taken to perfect this process. The researchers also found that in the cells the reprogramming was incomplete. This could have serious consequences if such cells were used for reproduction, highlighting the need for discussion on how to conduct this type of biomedical research safely and ethically.

'This involves many technical problems and ethical questions, and that is still a long way off. But in mice it has already been possible to fertilise an egg cell obtained in this way with a natural sperm cell,' commented Dr Arend Overeem, a stem cell biologist at the Leiden University Medical Centre who was not involved in the study (see BioNews 1104).

Understanding how eggs and sperm develop can provide researchers with insights into some causes of infertility. It also opens up possibilities for creating sperm and egg cells in a lab in future, which could significantly advance reproductive medicine and aid individuals with fertility issues.