Scientists can now create mice with two fathers

Scientists at Osaka University in Japan have just created baby mice with two dads. That’s right: these mice have two parents, and both parents are males.

How did they do it, and what might this mean for humans?

Well, as reported recently in the journal Nature, it wasn’t easy. The scientists fertilized 630 eggs to get just seven mouse pups, but all seven mouse pups appeared normal and grew into fertile adults.

Let’s dig into the process just a little bit. The research team, led by biologist Katsuhiko Hayashi, first took cells from male mice, and they had to somehow re-program the cells to create egg cells.

One thing about egg cells in mammals: they are always female. Or to be more precise, they have two copies of the X chromosome. Males have one X and one Y chromosome, and the male mouse cells in this experiment started out that way too.

Hayashi’s team first took cells from male mice and turned them into pluripotent stem cells–a special type of cell that can then be turned into many other types of cells, including eggs. Then they grew these cells in Petri dishes until some of them spontaneously lost their Y chromosomes. Now the cells had 1 copy of the X chromosome, but no Y.

That only got the scientists part of the way to where they needed to be. The team then used another genetic trick that induced some of these cells to pick up an extra X chromosome while they were replicating. At that point, they had created mouse cells with two X chromosomes: in other words, the cells were genetically female.

The next step was to convince these XX cells to turn into egg cells. They did that using additional genetic techniques to coax the pluripotent cells to divide and form egg cells, each of which had just one copy of every chromosome (as egg cells do), including the X chromosome.

Those were the hard parts. Once they had the egg cells, the scientists fertilized them with sperm from other males, and then implanted 630 fertilized eggs in female mice. It wasn’t a very efficient process, but it worked: seven of the embryos successfully matured into baby mice, which grew into normal, fertile adults. (Note that mice only take 3-6 months to reach maturity.)

You might be wondering if all mice (or other mammals) with two male parents would have to be males. Well no, not at all. Sperm cells, which come from males, have either an X or a Y chromosome. After fertilizing the eggs, which all have X, the result is either XX (female) or XY (male), depending on which chromosome the sperm carried.

The scientists who did this work emphasized that we’re still a long way from making it work in humans. Among other things, we’d have to be sure that all of the steps involved in turning the male cell into an egg didn’t create harmful mutations elsewhere.

You might also ask if this means that we can also create babies using two female parents. Well, probably yes, but not using the process described here: to create a baby from two females, we’d need to take a female cell (any cell would do) and then turn it into a sperm cell. This is possible too! As it happens, a 2021 paper from Emory University described how scientists have recently created sperm cells from pluripotent cells in rhesus macaques. If viable sperm cells can be created, then they can be used to fertilize eggs, which would give us offspring with two female parents. (In this case, all of the babies would be female.)

But at least in principle, it may soon be possible for two men to have a child where both of them are the child’s genetic father.