It is my great pleasure to be here to share some news from biology today with you. So, your life and mine start with this: the union of sperm and egg. The fertilization involves sperm from the father and egg from the mother. They meet in the usual way and...

the egg acquires the potential to give rise to individuals like you and me. If you trace back your generation, you are derived from your parents, and your parents are derived from your grandparents, and so on in the distant past. This perpetuity can only be achieved through what biologists like me call...

germ cell lineage. These are the only cells that are immortal among more than 200 types of cells in your body. The let die is you. So, these immortal germ cells are called gametes. They are very important, and we call them germline in our society. This unbroken line...

is under threat. The present generations are having children later and later, and the older germ cells are less likely to result in successful fertilization, which leads to the declining birth rate. It's not just a people continuous decrease in the reproductive rate of large livestock has...

resulted in huge economical losses. Setting aside human needs, there are endangered animals down to few individuals. How can we preserve them? That is where the assisted reproductive technology offered hope. Since Robert Edwards successfully combined human gametes in the dish, more than 12 million babies...

have been born through this technology called in-vitro fertilization. However, current assisted reproductive technology can only be applied if sperm and egg can be obtained from the body. If not, there are no options available. But I would ask now, can we create a gamete in the dish so this...

is a question so let's start with how the germ cells formed in the body after fertilization. Fertilize the egg undergo cell divisions and differentiate into the different cell types as it further developed. The original cell of eventual sperm and egg known as a primordial germ cell

emerge, then these primordial germ cells then differentiate into the primary egg known as oocyte in the female or spermatogonia, the precursor of sperm in the male. These egg and sperm mature over time, which is associated with the sexual maturation of

individuals. Now imagine if this entire process were to occur outside the body. So my team and I have been focusing on replicating this entire process in the dish, known as invitro gametogenesis. The key to generating the gametes in the dish is

a type of cells called pluripotent stem cells because they each have the ability to differentiate into any cell type in the body. Martin Evans showed that such a pluripotent stem cell could be derived from pre-implantation embryos in mice and James Thomson showed it could be done in humans.

Based on these breakthroughs, Shinya Yamanaka showed that any kind of cell in the body could be turned into pluripotent stem cells simply by expressing a specific set of proteins. These are called induced pluripotent stem cells and they possess the same

potential as those derived from the embryos. By using these pluripotent stem cells, we can hijack the germline during normal development. Cells receive a signal that guide their differentiation into the different types. By mimicking the right signals, pluripotent stem cells can be

directed along the pathway to differentiate into the egg or sperm. This has been successfully demonstrated in our laboratory by using mouse pluripotent stem cells. By providing appropriate signals, we were able to generate mature eggs from mouse pluripotent stem cells. Also to

achieve this, we created a mini ovary from pluripotent stem cells, allowing the oocytes to mature outside the body. Importantly, eggs produced in a dish are capable of fertilization and giving rise to yet more mice. Like this, these look the same as any other mice. They grow up,

they eat the food, they breed, and live. But in this case, the genetic makeup of this mice is the pluripotent stem cells growing in the dish. With this in-vitro genesis, the process of creating eggs requires only skin cells or other easily collectible cells from the body, even cells in urine. So this means

actually this kind of technology can be applied to various mammal species including humans, livestock, or even endangered animals. Several research groups have successfully produced the primordial germ cells from pluripotent stem cells. In all these cases, notably our laboratory is actively involved in depopulation efforts for the

northern white rhino. Sadly, there are only two females who remain on this planet. We have generated the egg precursors from the northern white rhino in these pluripotent stem cells and then currently creating a mini ovary system to mature these precursors into the

eggs. But we can go further than that. By using this technology, we can skip the sex-dependent reproduction. Today, gametes have different shapes and different functions based on the sex. This difference is genetically made by the sex chromosome. In humans, males have an X and a Y

chromosome and the female have two X chromosomes. From a genetic viewpoint, this is the only difference between male and female. But in addition to this, we can eliminate this difference. So our laboratory succeeded in switching from the XY chromosome to the XX chromosome. How did we

do that? Well, we took this cell from the male mice and then made induced pluripotent stem cells, which have X and Y chromosomes of course. Then we made a lot of these cells. In some of the population, unequal segregation of sex chromosomes occur during cell division, which means some XY

chromosome become one X chromosome, that then doubles and become two X chromosomes. We picked up a very rare population of these cells that have about two X chromosomes and we made the egg. The egg derived from sex-converted induced pluripotent stem cells behave exactly like eggs from

traditional females. We then fertilized the sex-converted egg with the sperm and this gave rise to typical healthy mice like this. They grow up, they eat the food, uh they mate and live long just like a conventional breed of mice. The only difference is these are derived from

that. Looking at the history of reproductive technology, like this technology is developed in the experimental animal like this, can eventually be applied to the human and other animals. Today, the production of eggs in the dish even from traditional male cells opens a new possibility for the

reproduction in the future. We can create a gamete in the dish and they can come from two fathers, two mothers, or perhaps other combinations. Thank you.

A Mouse With Two Dads — and a New Frontier for Biology | Katsuhiko Hayashi | TED

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