March 15, 2023

expert reaction to study attempting to generate functional mouse egg cells from male mouse stem cells

A study published in Nature looks at generating functional oocytes from male mice in vitro.

Prof Rod Mitchell, Professor of Developmental Endocrinology, MRC Centre for Reproductive Health, University of Edinburgh; and Consultant Paediatric Endocrinologist, Royal Hospital for Children and Young People, Edinburgh, said:

“Germ cells that will eventually become eggs or sperm arise from the same initial cell type.  Their early development does not depend on their sex chromosomes (XX or XY), but rather signals produced by the local environment in the ovary or testis.  In order to complete their development, the sex chromosomes become critical; XX germ cells will develop into eggs and XY germ cells into sperm.

“This elegant study used stem cells from male (XY) mice and developed a culture system which resulted in loss of the Y chromosome.  They then used a chemical that led to a second X chromosome in some of the cells, essentially creating XX stem cells.  These XX cells could be converted into germ cells and mixed with cells from an ovary to become eggs, which were able to be fertilized and generate live mouse offspring.

“This study is particularly neat because it takes advantage of errors that are known to occur during culture of XY cells, which lead to loss of the Y chromosome and subsequent gain of a second X chromosome, resulting in XX cells that are capable of generating live offspring.

“This is a very important breakthrough for the generation of eggs and sperm from stem cells.  It has potential applications in animals, including for preservation of endangered species.

“However, its potential application for humans (e.g. for same-sex couples) remains to be seen.  In the mouse study, very few of the embryos generated using mouse cells resulted in live offspring and the final steps required to convert germ cells into eggs have not been reliably reproduced using human cells.

“In addition to the technological challenges, the safety of the approach and the subsequent health of offspring would need to be robustly tested before this could ever be applied to humans.”

‘Generation of functional oocytes from male mice in vitro’ by Kenta Murakami et al. was published in Nature on Wednesday 15 March 2023.

DOI: 10.1038/s41586-023-05834-x

Declared interests

Prof Rod Mitchell: “None.”