In a first, scientists in Japan led by Professor Hayashi of the Osaka and Kyushu Universities have successfully created a litter of mice with two dads. The egg and the sperm cell came from male mice. You might be wondering – how could the male mouse possibly produce egg cells? Let’s talk about the biology, what it means for society, and what our future might possibly hold. Keeping with this article’s theme of birthing offspring, a bonus anecdote about virgin births is included at the end.

Cellular Acrobatics

Your high school biology teacher was correct – males do not produce egg cells. Phew! Let’s recollect some biology to contextualize this work. All human cells contain 23 pairs of “noodles” called chromosomes (Fig. 1 below). Of the 22 numbered pairs of noodles, we get one of each pair from mom, and one of each pair from dad. Pairs 1-22 determine you height, hair color, lactose (in)tolerance, and a whole host of other things. Pair 23 is special and determines your biological sex. If your 23rd pair is X-X, you’re born biologically female. If it’s X-Y, you’re male. We need an egg cell and a sperm cell to produce a zygote that eventually becomes a baby. So how did these scientists get male mice to produce egg cells?

Well…they didn’t. Instead, they used cellular (re-)engineering to convert skin cells from a male mouse’s tail into female egg cells. These egg cells were then fertilized by a male sperm cell, which produced a litter of mice. Let’s take a deeper dive.

Complexity and Improbability

Saying “they converted male skin cells into female egg cells and then produced mice with two dads” sounds like a simple process, but it was anything but simple. Here’s how they beat the odds:

The scientists took skin cells from the tail of a male mouse and, in a petri dish, turned them into induced pluripotent stem cells. [Aside: Cellular reprogramming was pioneered by Dr. Shinya Yamanaka, who won the Nobel Prize for his work in 2012] These stem cells are unique because they can be converted (i.e. differentiated) into any type of cell based on their growth conditions. During this cellular reprogramming, 6% of the XY cells in their petri dish spontaneously lost their Y chromosome, leaving behind only an X chromosome and yielding an XO genotype.

While replicating, a few (~2%) of the XO cells erroneously duplicated the X chromosome to produce an XX genotype. A drug called reversine boosted this percentage of XX cells further. This fraction of mouse cells with two X chromosomes that was genetically female was separated from the vast majority of XO cells using a technique called flow cytometry. Finally, the researchers converted the XX cells into germ cells, and programmed them to turn into egg cells. Once fertilized with sperm and implanted into a mouse uterus, the eggs generated live offspring (Fig. 2 below). Importantly, the litter of five mice included male and female mice. Furthermore, these mice were fertile and could produce their own offspring. The grey mouse (rightmost) in the image actually became a proud dad shortly after!

What this means for society?

Someday, Prof. Hayashi’s research could allow for the possibility that same-sex couples can have a baby who shares both parents’ genes.
Noteworthy conundrum: It will be very challenging to flip the script and instead make sperm from female cells. Sperm cells contain an X and Y chromosome – given that female cells (XX) contain no Y chromosome, somehow we will need to conjure up a Y chromosome in female cells for this to work.
This research also expands the possibilities for future fertility treatments – if one individual in a couple is infertile, it would be possible to use their cells to generate sex cells (eggs and sperm) for fertility treatments.
Finally, this might even help prevent extinction of endangered animals. For critically endangered animals, we no longer need a viable, sexually-mature male and female animal of the species to mate (a process that any zookeeper will tell you can be challenging by itself). I hope we’re establishing biobanks with genetic specimens of all known living creatures so we can try hitting the ‘Undo’ button on species that go extinct in the future.
Important context: Any biologist worth their salt will tell you that this research is decades away from application for humans. Humans are much more complex, take much longer to mature sexually, and a lot of processes used in this research haven’t been successful in humans (yet).

Ethics pause: This work raises important ethical and legal questions that we must consider. With the advent of genome engineering with CRISPR-based technologies, a lot that we chalked off as science fiction is now within reach – designer babies, embryo banks (akin to sperm banks), etc. Further, who has ownership of your genome? In an extreme case, what if your skin cells were swiped off a coffee mug and used for making a baby? The legal landscape on these new age developments is murky. Continuing conversations by bioethics leaders around the world are crucial to preventing irreversible mistakes.
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BONUS! The Fruit Fly Virgin Mary

Scientists at the University of Cambridge were able to induce virgin birth in fruit flies (species: Drosophila melanogaster), coming closer to understanding a process called parthenogenesis (Sperling, et al.)
Parthenogenesis: An asexual reproduction in which a female can produce an embryo without fertilizing an egg with sperm. In Greek, it means the virgin creation.
Furthermore, the offspring produced was viable, and could in turn also have virgin births without ever interacting with a male fly.

Important context: Virgin births occur naturally in some animal species (bees, some lizards, fish, etc.) Virgin birth has been induced in species like mice before as well. However, this is the first report where scientists isolated specific genes to make parthenogenesis a lasting and inheritable trait that is incapable of this type of reproduction. If you want to learn more, check out Reference #2 below or this useful synopsis.
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Catch you next time.

Sincerely,
Your neighborhood scientist

References:
(1) Murakami, et al. Generation of functional oocytes from male mice in vitro. 2023, Nature. 615: 900-906.
(2) Sperling, et al. A genetic basis for facultative parthenogenesis in Drosophila. 2023, Current Biology. 33 :3545–3560.