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 basicaly 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
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