From research that could stimulate the social debate around sex, gender and family, we now have a way of converting male (XY) mouse stem cells into functional female (XX) egg cells. The work published in Nature1 shows that, when fertilised, around 1% of the resulting mouse embryos produce healthy offspring.
Male and female gametes - sperm and eggs - both derive from a type of stem cells known as primordial germ cells. Differentiation of these stem cells into gametes is a function of sex chromosomes, and the nature of primordial germ cells can change in response to environmental influences.
The new research led by Katsuhiko Hayashi at Kyushu University in Japan marks the first time that stem cells from adult male mice have been turned into eggs. The process is a variation on the technique known as in-vitro gametogenesis, in which gametes are created from unspecialised cells taken from body tissue that may be manipulated into, say, blood cells or neurons.
Instead of using stem cells from female mice, Hayashi and his team discarded the Y chromosome from male mouse cells, and embedded the remnant cells in artificial ovaries also produced from stem cells. The manipulated male cells then developed into egg cells, or oocytes. Some 630 embryos were transplanted into surrogate female mice, resulting in seven healthy pups that were fertile as adults.
Do not expect the technique to be transferred easily from mouse to man, however. There are huge biological differences between mice and humans, not least the much slower development of human cells, and the challenge in deleting Y chromosomes and duplicating X chromosomes without causing adverse genetic mutations along the way. Research on monkeys is a possible first step once the ethical issues are clarified and technical processes approved.
Murakami et al., “Generation of functional oocytes from male mice in vitro”, Nature (2023); doi:10.1038/s41586-023-05834-x.