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Chinese scientists make mice with only father and no mother

via:学术经纬     time:2018/10/12 10:32:52     readed:75

This heavy research was published online today in the Cell, a cell-stem cell.

▲The three correspondents of this study are Li Wei, Zhou Qi, and Hu Baoyang (Source: Institute of Zoology, Chinese Academy of Sciences)

Can you breed more without the other half?

The combination of men and women can give birth to children, which seems to be an irrefutable truth for human beings. But if we look at the entire animal world, we can find that "two individuals with different genders" is not a necessary condition for breeding offspring. For many reptiles, amphibians, and even fish, you can produce many offspring on your own.

_Some reptiles indicate that reproduction does not require the involvement of the other half (image source: Pavelevela [CC BY-SA 4.0 (https://creativecommons.org/licenses/by-sa/4.0)], from Wikimedia Commons)

For example, in 2010, scientists discovered a female red-tailed python (Boa constrictor) Through the asexual reproduction, 22 small snakes were born. Subsequent chromosomal analysis confirmed that the birth of these offspring did not depend on male participation (the male snake's chromosome is ZZ, the female snake's chromosome is ZW, and the asexual reproduction of the offspring is a rare WW type). In this regard, in addition to shouting magic, scientists do not understand the biological mechanism behind it.

Can higher animals breed asexually?

Since reptiles can be asexually propagated, can mammals do the same? Unfortunately, under natural conditions, this seems like an impossible task. The reason for this is a phenomenon called genomic imprinting. This refers to genes provided by fathers or mothers, some of which are "closed" and inactive. Only when the genes from both parents come together can they complement each other and let the offspring develop normally.

The birth of a new life requires the participation of both parents, and there is a reason for biology (Source: Pixabay)

For example, one of the human beings is calledIGF2The genes that play a vital role in development and growth. But the interesting thing is that only from the fatherIGF2The gene is active. Despite the mother's offerIGF2Genes can be identical to the father's genes in terms of DNA sequences, but they are shut down and unable to function. Similarly, some genes can only function if they are inherited by their mothers.

This explains that in the natural environment, the birth of a mammal requires the participation of both parents. If only the father or mother provides genetic material, there will be some genes that cannot be expressed smoothly, causing defects and affecting embryonic development.

The birth of "Hui Ye Ji"

If we can change the "genomic imprint" and make the genes from the mother look like the father's genes, can we make mice with only mothers and no fathers? Using this method, a Japanese team took the lead in success in 2004 – they created a mouse with two mothers but no father. The scientists named the mouse "Hui Ye Ji", a baby born in bamboo in Japanese mythology. The mouse survived to adulthood and proliferated normally with other mice, giving birth to offspring.

"But this mouse still has some defects, and its method is difficult to apply, very unrealistic." Researcher Zhou Qi said.

This is indeed a fact. In order to successfully produce "Hui Ye Ji", the Japanese team produced a total of 460 mouse embryos, only 10 were born successfully, and only one survived to adulthood. Obviously, this technology still has a lot of room for improvement.

Breakthrough of Chinese scientists

And this is where the breakthrough of Chinese scientists lies. The team found that haploid embryonic stem cells carry fewer "genomic imprints." "We found that haploid embryonic stem cells are closer to primordial germ cells, which are precursors to eggs and sperm," said researcher Hu Baoyang. "The 'genomic imprint' found in gametes (eggs and sperm) was 'erased'. ."

▲ Graphic of this study (Source: Reference [1])

In haploid embryonic stem cells from female mice, scientists used the advanced gene editing tool CRISPR-Cas9 system to remove three hard-hit areas of “genomic imprinting”. In this way, the genetic material in these stem cells can maintain good gene expression activity.

Subsequently, the scientists injected the genetic material of these stem cells into the M2 phase oocytes to induce embryonic development and formation. The mice born in this way carry the genetic material of two mothers. The researchers eventually produced 210 embryos, 29 of which were born smoothly, many of which grew to adulthood and gave birth to their offspring. It can be seen that the success rate of this technology has to come even higher.

▲Only mothers, mice without fathers are all normal, and they have successfully produced offspring (Source: Leyun Wang, Institute of Zoology, Chinese Academy of Sciences)

If the mice that make "only the mother, no father" are complicated enough, then the mice that make "only the father, no mother" are more complicated...

Using a similar approach, scientists removed up to seven “genomic imprints” in haploid stem cells from male mice. Subsequently, they injected the genetic material with the sperm of another male mouse and injected it into an egg without a nucleus. Subsequently, this cell develops into an embryo in the body of a surrogate mouse, giving birth to new mice with only the genetic information of two fathers.

▲ Creating a mouse with only a father and no mother can be said to be a breakthrough (Source: Leyun Wang, Institute of Zoology, Chinese Academy of Sciences)

This method is much more difficult. Of the 477 embryos, only 12 were successfully born. Among them, 10 mice died 2 days after birth. The remaining 2 mice did not live to adulthood. Subsequent research found that even after experiencing so many genetic editing, some genes were not successfully expressed. This may be the reason why mice with "only father, no mother" are early.

to sum up

Many biologists point out that this groundbreaking study once again proves that "genomic imprinting" is the reason that hinders the solitary reproduction of mammals. Even large-scale genomic transformations cannot completely eliminate these imprints. This also points to the direction of the future of science.

“This study reveals various possibilities,” commented Li Wei. “We saw mice with only two mothers whose defects could be eliminated. We also saw that by modifying the 'genomic imprint', we can overcome only Reproductive disorders in two fathers. We also revealed important imprinting regions that block the parthenogenesis of mice, which makes sense for both 'genomic imprinting' and animal cloning."

It should be noted that this study is far from human application. Regardless of the technical difficulties in the mouse system, even if we can efficiently produce parthenogenetic mice, the transformation from mice to humans still has technical, ethical, and legal challenges. All of this requires scientists, bioethicists, and legal experts to work together.

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