Mice with two fathers and no mother have now had offspring of their own. The study is a breakthrough in androgenesis – that is, asexual reproduction using only genetic material from male animals.
We’ve seen androgenesis in mice work in the lab before: earlier this year, researchers were able to produce mice from genetic material from two males, by fertilizing eggs missing the mother’s genetic material. However, the resulting offspring were infertile and unable to reproduce.
In this latest study, led by a team from Shanghai Jiao Tong University in China, that’s changed – though a lot of the techniques used were similar to the earlier experiments. They focused on editing specific imprinting control regions (ICRs), sequences of DNA that act as gene control switches.
The standard mix of male and female genes provides a healthy balance of ICR coding – but if only mom or dad genes are used, this coding goes haywire. That results in severe embryo issues and death, so scientists have been trying to reprogram these ICRs with precise gene editing techniques.
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“We attempted to improve the development of androgenetic embryos by restoring the epigenetic status of these ICRs,” write the researchers in their published paper.
“Our efforts enabled us to generate androgenetic mice that can develop to adulthood and are fertile, using the genetic materials derived from two sperm cells.”
Sperm from two male mice was injected into mouse eggs, with the nucleus removed – the part holding the female DNA. The researchers then edited seven specific ICRs, abnormalities in which had previously been found to have the most severe consequences. These eggs were then implanted in other female mice.
This process produced three live mouse births from 259 implanted blastocysts (early embryos), and only two survived to adulthood. That might not sound like a particularly impressive success rate, but it’s above zero – and the two survivors then went on to reproduce normally and have healthy mouse pups.
While there’s obviously lots of room for improvement in terms of how many mice are born and live to see adulthood, and how exact the ICR editing techniques can be, it shows that this approach to imprint editing can work.
This is something that’s easier to do when there are two mothers involved, by the way: the edits required are fewer and easier to carry out. That the researchers were able to get it to work with two fathers adds to the importance of the study.
Now we shouldn’t get ahead of ourselves: this is still a very difficult process in mice, which fails a lot of the time, and it’s going to be a long while before scientists can think about whether the same techniques could be used for human embryos.
Even then, there will be a host of ethical and philosophical questions to address, but eventually this research could drive improvements in fertility treatments and our understanding of congenital disorders.
“Although the efficiency is low at present, this finding may be an important step toward achieving mammalian androgenesis,” write the researchers.
The research has been published in PNAS.
