Mouse eggs made from mouse stem cells matured in vitro

An in vitro gametogenesis (IVG) breakthrough has been achieved as mouse stem cells have been used to create egg cells that have successfully developed into live mice when used in IVF.

A team led by Professor Katsuhiko Hayashi and Dr Takashi Yoshino at Kyushu University in Fukuoka, Japan, conducted the research which has allowed the development of mouse egg cells entirely in vitro. Previously the team had developed a process by which they could develop mouse egg cells from embryonic stem cells and induced pluripotent stem (iPS) cells by incubating them in ovarian follicular tissue taken from mice. This research represents the next step towards developing entirely in vitro-derived gametes. Their results, along with commentary, have been published in the journal Science.

'It's a very serious piece of work,' Professor Richard Anderson, chair of clinical reproductive science at the University of Edinburgh, who was not involved in the study told STAT News. 'This group has done a lot of impressive things leading up to this, but this latest paper really completes the in vitro gametogenesis story by doing it in a completely stem-cell-derived way.'

In mammals, the ovarian follicle is essential for the differentiation of an initial germ cell that develops inside a female fetus into a mature egg in an adult female capable of being fertilised and developing into an embryo. The initial germ cell must undergo meiosis, which is made possible by the cell signalling induced by the environment found in the ovarian follicle. It has proved particularly difficult to achieve this process in vitro, but it is essential if gametes are to be produced in the lab outside of the body.

To overcome this limitation the team placed mouse stem-cell-derived egg cells into conditions that mimicked those found in the ovarian follicle. Researchers observed that follicle-like structures were formed they named rOvaroids, in which meiosis was observed to take place in the oocyte, and when these mature eggs were used to create embryos with sperm using IVF, live births were observed for 5.2 percent of the embryos. All the live births resulted in mice that grew to adulthood.

The team is currently looking at repeating the process in marmoset monkeys. Professor Hayashi told STAT News: 'The issue is the quality of the in-vitro oocyte. That could take a long, long time to verify.'