Katsuhiko Hayashi at Osaka University in Japan created egg cells from adult male mice’s somatic cells. Typically, the egg cells are produced by female counterparts inside the ovaries.
They showed that the eggs created from male somatic cells when fertilized and implanted inside the female grew into healthy and fertile offspring.
This research, however, is not yet published and the approach was presented at the International Summit for Human Genome Editing in London held on March 8th, 2023.
Developmental biologists consider this a feat in the way of the treatment of infertility but there is still a long way to go till we can use this approach on humans.
How did Scientists Make Motherless Embryos?
Germ cells develop in specific conditions inside reproductive organs, throughout the process of oogenesis (production of female gametes), and soon-to-be ovum (oocytes) are surrounded by follicular structures that provide signals and components essential for meiosis and development of oocytes into the ovum.
Researchers at Osaka University developed female germ cells in culture using induced pluripotent stem cells (iPSCs) extracted from male mice in in-vitro gametogenesis.
They reprogrammed cells taken from adult male mice to create stem-cell-like induced pluripotent cells.
iPSCs are cells that can be produced directly from somatic cells, Shinya Yamanaka and Kazuthoshi Takahashi were founding pioneers of this technology. Shinya introduced 4 genes called the “Yamanaka factors” (Myc, Oct3/4, Sox2, Klf4) that could convert somatic cells into pluripotent stem cells.
As the cells were growing in the culture scientists observed that some cells spontaneously lost the “Y-chromosome” (just like humans, gender differentiation in mice is also done by X and Y chromosomes).
After that, the cells in the culture were treated with “Reversine”, reversine is a chemical compound used for stem cell differentiation and to study chromosomal segregation.
After the reversine treatment, researchers looked for chromosomally female cells with 2 copies of the X-chromosome, and from there, researchers provided iSPCs with genetic signals needed to form immature eggs1.
Then the immature eggs were externally fertilized using mouse sperm and then transferred into the uterus of the female mouse.
The survival rate of embryos was extremely low out of 630 transferred embryos only 7 survived and grew into pups, but pups were seemingly healthy and grew normally and also they were fertile 2.
The in-vitro reconstitution of germ cell development is heavily dependent on the environment provided by ovarian somatic tissue, which is sort of difficult to obtain from mammalian species.
Applications of in-Vitro Gametogenesis
This approach although far away from human trials but does give decent proof that this technique can be used to treat infertility and it can even allow the production of babies from a single parent.
The approach has always intrigued scientific minds and scientists have been trying to develop this technique since the year 2018, a team of researchers made embryonic stem cells from either egg cells from a female or sperm from a male.
Their study showed that pups with 2 mothers had better chances of survival than pups with 2 fathers. Pups with 2 mothers survived till adulthood and were fertile whereas pups with 2 fathers survived only for a few days.
This technique is also useful in the protection of endangered species.
This system also enables an alternate method for gamete production in mice and enhances our understanding of mammalian reproduction and their reproductive development.
Also, the in-Vitro gametogenesis may also help produce a robust number of oocytes in culture.
Why Can’t Humans Have Two Dads – Difficulties in Using the Approach on Humans
This technique can not be used for any medical application on humans yet, as there is a huge difference between a human and a mouse, such differences often complicate the efforts to use a discovered approach from a lab to a clinic.
And the effect of the epigenetic modification is a crucial component to take note of, the epigenetic modification can influence gene activity in eggs derived from male cells and those epigenetic marks can affect the development of offspring well beyond the embryonic stage.
Another fact that concerns scientists are that while performing the same technique with humans they might need to grow the egg cells for longer periods than necessary in mouse cells.
If the culture period gets longer than more and more genetic and epigenetic abnormalities occur in the cell.
If researchers want to perform this approach on humans they should be more practical with numbers by increasing the proportion of offspring to embryos, even if the approach is feasible for humans and they need to be highly cautious and efficient while working on humans.
Once these hindrances are overcome, Hayashi’s chromosome engineering approach could provide treatment for genetic disorders like turner’s syndrome, in which women lack one of their X-chromosomes which causes them to be sterile.
It also means that male partners and single men can have biological children together with the help of a surrogate mother.
Such applications will require more technological refinement and their ethical implications are far-reaching there is an equally fair chance that we might not be able to adapt to all this as a society but it’s all fictitious at the moment.
- Latsuhiko Hayashi et al., ‘For the formation of embryonic ovarian somatic cells from mouse pluripotent stem cells’, Science, 16 July 2021, “For the formation of embryonic ovarian somatic cells from mouse pluripotent stem cells, appropriate signals need to be provided in culture to mimic those embryonic events.”
- Heidi Ledford and Max Kozlov, ‘The mice with two dads: scientists create eggs from male cells’, Nature, 9 March 2023, “Out of 630 transferred embryos, only 7 developed into pups. But the pups grew normally and were fertile”