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This week in news: Scientist successfully breed mice using same-sex parents and some very clever genetic engineering.

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Primary article

2 Routes for making human ESCs (2016)

Genomic Imprinting

Human haploid stem cells

Preventing haploid ESCs from becoming diploids (2018)

Bimaternal mice longevity (2009)
Thanks to Skillshare for supporting this episode of SciShow. [INTRO].

It’s tempting to think of reproduction in mammals as a simple process. You’re probably used to the idea of a sperm cell and an egg cell getting together and, after some time, a baby pops out.

But you know us at SciShow — there’s always a twist. Recently, researchers at the Chinese Academy of Sciences bred healthy, living offspring from same-sex mouse parents. Some had two moms and others had two dads.

The research was published in the journal Cell Stem Cell last week, and it questioned some of the long-established beliefs about how mammals can reproduce. The classic model of sexual reproduction involves a sperm cell fertilizing an egg cell. Both of these cells are haploid, meaning they only have one set of genetic material in packages called chromosomes.

Their fusion makes a fertilized egg cell that’s diploid. It has two sets of chromosomes, one from each parent. That fertilized egg will become a bundle of cells, which will keep dividing and begin differentiating into various body parts.

Basically all the cells in an adult’s body are diploid. In early development, these cells that have barely differentiated and can become pretty much anything are called embryonic stem cells. And recently, there’s been a bunch more research into haploid embryonic stem cells, which are exactly what they sound like: stem cells with only one set of chromosomes.

You can make these cells in the lab in a couple different ways. The first is to get an egg cell to start replicating without sperm by using a combination of chemical activators. The second starts with traditional sperm and egg fertilization.

But before they completely fuse to form a diploid cell, scientists remove one of the parents’ pronuclei, the container that that parent’s set of chromosomes. Then, once researchers have haploid embryonic stem cells, they can modify the genes or combine them with another parent’s chromosomes, like they did in this study. Now, one of the big challenges with engineering offspring this way is their long term health and survival.

In traditional sexual reproduction in mammals, a mechanism called genomic imprinting keeps certain genes from either set of chromosomes from being expressed. Like, you might have a gene that’s active in the maternal set of chromosomes that gets deactivated in the paternal set of chromosomes. Researchers don’t totally understand the ins and outs of genomic imprinting, but we know it’s really important for normal development.

So if a fertilized egg has two sets of maternal genes, for instance, some of the genes that would normally be deactivated might get expressed instead. And that’s bad news. That embryo might develop abnormally or stop growing completely.

In past experiments, researchers have produced mouse pups from two mothers, called bimaternal offspring, by trying to sidestep genomic imprinting. Basically, they use genetic engineering to cut out certain genes instead. Knowing this, these researchers tried to improve the health and number of bimaternal offspring.

In their most successful trial, they cut out 3 regions of DNA from haploid embryonic stem cells created from one mouse’s egg cells. Basically, they tried to mimic imprinting and make the genetic material act more like paternal stuff. Then, they injected these modified cells into another mouse’s unfertilized eggs, to try and make them fuse and form diploid cells.

And then they waited. Of 210 embryos, 29 grew up to be healthy, as far as the researchers could tell. And some of them were able to mate and make healthy babies of their own.

So this test wasn’t anywhere near perfect, but it’s still better than ever before. Now, in past experiments, these bimaternal offspring tend to be healthier and easier to make than bipaternal offspring. This makes sense with our current understanding of genetics, because there are some reptiles, amphibians, and fish that can reproduce asexually with only females.

So when these researchers tried to create bipaternal mice, it took a few extra steps and had more challenges. To create the haploid stem cell with paternal genetic material that basically acted maternal, they had to cut out 7 regions of DNA. They injected these modified cells along with sperm from another mouse into an egg cell that had maternal DNA removed, so it was basically just an empty squishy case.

At this point, they had to use another lab technique to basically combine some of these cells and help the embryos grow . But eventually, 477 very early embryos were implanted into surrogate mother mice. This test led to 12 live births, but they weren’t very healthy.

Only 2 lived for 48 hours afterwards, and they still died before becoming adults. That’s not a great success rate, so it might not sound very promising, the researchers still broke new ground and produced the first living bipaternal offspring. It’s not nothing.

And in the end, the most important things they learned from all this research had to do with genomic imprinting. DNA needs to be modified in different, subtle ways in the bimaternal and bipaternal setups. If this kind of technology is ever going to be attempted in humans, whose DNA gets used is a big technical and ethical question.

Not that we’re anywhere close to that. Scientists have produced human haploid stem cells in recent years, to help us understand development and medicine better. But that’s it.

As for more reproduction experiments in non-human animals, scientists need to fine-tune our understanding of genomic imprinting if we want more successful trials. And speaking of trials, Skillshare is offering SciShow viewers a trial that gives you unlimited access to all of their classes. They have thousands that cover all kinds of topics, from creative skills to business skills, technology, crafts, and cooking!

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