Mice without a mother: scientists have grown healthy mice from two spermatozoa

The scientific world has officially crossed another biological boundary. Researchers from the Centre for Reproductive Medicine at Shanghai Jiao Tong University have created mice that were born... from two males. No eggs, no mothers. Just two sperm cells, a little bit of genetic magic and a lot of patience.

What is known

The main obstacle to such "daddy's offspring" was the mechanism of genomic imprinting - epigenetic chemical marks in DNA that turn genes on or off depending on whether they are inherited from the father or the mother. Without the right combination of these marks, the embryo usually does not survive. In "scientific" terms, the main problem is that there are special "marks" in DNA that tell genes when to work and when to be silent - and it depends on whether the genes came from mum or dad. If these marks are missing or wrong, the embryo simply cannot develop and dies.

The team, led by Professor Yanchang Wei, solved this problem by targeted methylation editing in seven critical genomic regions - the so-called ICRs (Imprinting Control Regions). For this purpose, two CRISPR-based systems were used: one for removing methylation marks (dCas9-Tet1) and the other for adding them (dCpf1-Dnmt3).

The methodology was as follows: the nucleus was removed from the egg, and the heads of two spermatozoa were injected instead - one from a C57BL/6 laboratory mouse and the other from a wild-type CAST mouse. Then, the epigenetic marks were chemically reprogrammed, making one of the DNA copies behave as if it were the "mother's".

And the result?

Out of 587 embryos created, only 3 reached the birth stage, and two of them survived to adulthood. They were completely healthy, had normal weight and size, and - most importantly - were fertile, i.e. capable of reproduction.

One male eventually gave birth to 9 mice, and the other - to 6.

However, the success was partial: most of the embryos died during intrauterine development. The reason is the extreme difficulty of simultaneously reprogramming seven key DNA regions at once.

What does this mean for science?

• This is the world's first successful creation of viable and fertile mice exclusively from male DNA.
• It has been confirmed that imprinting is the barrier to same-sex reproduction in mammals, not something else.
• Although the application of this approach to humans (or at least to large animals) is still a long way off, the study opens the door to a deeper understanding of epigenetics, imprinting, and even potential future therapies for infertility.

Source: PNAS (Journal of the National Academy of Sciences of the USA)