Mouse pups with same-sex parents born in China using stem cells and gene editing

October 11, 2018, Cell Press
A bipaternal mouse pup (born to two fathers). Credit: Leyun Wang

Researchers at the Chinese Academy of Sciences were able to produce healthy mice with two mothers that went on to have normal offspring of their own. Mice from two dads were also born but only survived for a couple of days. The work, presented October 11 in the journal Cell Stem Cell, looks at what makes it so challenging for animals of the same sex to produce offspring and suggests that some of these barriers can be overcome using stem cells and targeted gene editing.

"We were interested in the question of why mammals can only undergo sexual reproduction. We have made several findings in the past by combining reproduction and regeneration, so we tried to find out whether more normal mice with two female parents, or even mice with two male parents, could be produced using haploid with gene deletions," says co-senior author Qi Zhou.

While some reptiles, amphibians, and fish can reproduce with one parent of the same sex, it's challenging for mammals to do the same even with the help of fertilization technology. In mammals, because certain maternal or paternal genes are shut off during germline development by a mechanism called , offspring that don't receive genetic material from both a mother and a father might experience developmental abnormalities or might not be viable. By deleting these imprinted genes from immature eggs, researchers have produced bimaternal mice—mice with two mothers—in the past. "However, the generated mice still showed defective features, and the method itself is very impractical and hard to use," says Zhou.

A healthy adult bimaternal mouse (born to two mothers) with offspring of her own. Credit: Leyun Wang

To produce their healthy bimaternal mice, Zhou, co-senior author Baoyang Hu, co-senior author Wei Li, and their colleagues used haploid embryonic stem cells (ESCs), which contain half the normal number of chromosomes and DNA from only one parent and which the researchers believe were the key to their success. The researchers created the mice with two mothers by deleting three imprinting regions of the genome from haploid ESCs containing a female parent's DNA and injected them into eggs from another female mouse. They produced 29 live mice from 210 embryos. The mice were normal, lived to adulthood, and had babies of their own.

One advantage of using haploid ESCs is that even before the problematic genes are knocked out, they contain less of the imprinting programming that ultimately causes maternal- or paternal-specific genes to be expressed. "We found in this study that haploid ESCs were more similar to primordial germ cells, the precursors of eggs and sperm. The genomic imprinting that's found in gametes was 'erased,'" says Hu.

Twelve live, full-term mice with two genetic fathers were produced using a similar but more complicated procedure. Haploid ESCs containing only a male parent's DNA were modified to delete seven key imprinted regions. The edited haploid ESCs were then injected—along with sperm from another male mouse—into an egg cell that had its nucleus, and therefore its female genetic material, removed. This created an embryo containing only genomic DNA from the two male parents. These embryos were transferred along with placental material to surrogate mothers, who carried them to term.

A healthy adult bimaternal mouse (born to two mothers) with offspring of her own. Credit: Leyun Wang

These pups survived 48 hours after birth, but the researchers are planning to improve the process so that the bipaternal mice live to adulthood. Similar results were achieved in 2011 but using a method that relied on a female intermediary produced from the first father's stem to mate with the second father. That method sidestepped the problem of genomic imprinting but presents ethical and practical hurdles if this technology were to ever be considered for humans.

Li notes that there are still obstacles to using these methods in other mammals, including the need to identify problematic imprinted that are unique to each species and concerns for the offspring that don't survive or that experience severe abnormalities. They do hope, however, to explore these techniques in other research animals in the future.

"This research shows us what's possible," he says. "We saw that the defects in bimaternal mice can be eliminated and that bipaternal reproduction barriers in mammals can also be crossed through imprinting modification. We also revealed some of the most important imprinted regions that hinder the development of with same sex parents, which are also interesting for studying genomic imprinting and animal cloning."

Explore further: First 'haploid' human stem cells could change the face of medical research

More information: Cell Stem Cell, Li et al.: "Generation of Bimaternal and Bipaternal Mice from Hypomethylated Haploid ESCs with Imprinting Region Deletions" www.cell.com/cell-stem-cell/fu … 1934-5909(18)30441-7

Jian Min Deng et al, Generation of Viable Male and Female Mice from Two Fathers1, Biology of Reproduction (2010). DOI: 10.1095/biolreprod.110.088831

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betterexists
1 / 5 (1) Oct 11, 2018
There are Various kinds of Mammals.
Only way to improve this field fast is to start working similarly on SEVERAL Mammalian Species.
Surveillance_Egg_Unit
1.7 / 5 (6) Oct 11, 2018
Should have been done on jonesdave's ancestors.

But what is the purpose in all this tomfoolery of unnatural procreation? Surely, these 'scientists' don't really think that two women can impregnate each other sexually. Nor can two males.
So what's the point and what is the gain?

Ot is it their goal to please and assuage the LBGTQRSWXYZ popularions of Earth? Does China's President Xi know about this? And would he approve this procedure to be done on humans?
rrwillsj
3.7 / 5 (3) Oct 11, 2018
Well segue, considering the deep level of ignorance of our own dearly bought and sold Bogus POTUS?

Why ever would you afflict the scientific and medical fields of any nation with interference from those most incompetent to claim a false authority to meddle in matters for which they have no training?
Surveillance_Egg_Unit
2.6 / 5 (5) Oct 11, 2018
Well, you see, rrwilliejoe - the nation of my origin is already quite a bit in the throes of Socialistic ideology and madness, running toward the cliff of unstoppable immigration from war-torn countries of the Middle East and Africa, much like lemmings in a mad dash toward eventual destruction. Western Europe and the UK are doing it wrong, much to the chagrin of their own White populations who really have no desire to host the cultures of rape, paedophilia, pederasty, and eventual "religion of peace (Muslim) forced upon the native white Europeans and gentle Englishmen.
I have far more respect and admiration for your American President than I have for either Theresa May or Angela Merkel. At least I know that I am relatively safe here in the States, unless your anti-US Constitution Democrat Party and its insane constituents gain enough power to turn the US into an eventual "shlthole" that has been well described by those with great foresight.
Surveillance_Egg_Unit
2 / 5 (4) Oct 12, 2018
-contd-
But you may get what you wish for, rrwilliejoe, as the news has been of late, that American White males, at an increasing level, have been found to have diminished sperm counts, thereby having a lesser chance of procreating in the normal heterosexual process. I am unsure if the same problem is occurring amongst Black, Latinos and Asian men. It may be that American white males are less inclined now for fatherhood, especially with the insidious climate of the man-hating Feminazi movement in the States, of which, I am sure, you are a part of.

As President Trump is already a father of 5, his sperm count is no longer of any consequence.
But in this coming midterm election, I will vote for the first time and be glad that I have more options than I had at home.

rrwillsj
1 / 5 (1) Oct 12, 2018
aegue, as trumpenella's offspring are notoriously sub-intelligent criminals. Maybe your belief in the anti-science of eugenics finds validity ib America's First Crime Family.

As for your inferiority-complex driven cowardice with women, coloreds and and anyone who doesn't need to use all their fingers and toes to count to twenty? It's way past time for you to grow a backbone.

All that ideological baggage of political correctness that burdens your shriveled soul? That's your problem to deal with. Or at least, come to terms with if you have any capacity for self-awareness.
Thorium Boy
3 / 5 (2) Oct 13, 2018
Nothing was wrong with eugenics, there is nothing worse than forcing a (will be miserable) life onto a sub-standard individual. If Hitler hadn't been born and tainted the science, they'd still be sterilizing imbeciles in the West just like they used to.
ShotmanMaslo
1 / 5 (1) Oct 13, 2018
But what is the purpose in all this tomfoolery of unnatural procreation? Surely, these 'scientists' don't really think that two women can impregnate each other sexually. Nor can two males.


You dont know that, if this research progresses then maybe it will be possible in humans, too. Anyway, basic research is more than enough purpose on its own.
rrwillsj
1 / 5 (1) Oct 13, 2018
To understand the consequences of the pseudo-science if eugenics, one should consider the disastrous effect upon racehorses & housepets.

The foolish attempt to breed speed and form to an official licensed standard based on the Stud Book set by racist dolts? Resulted in sickly, fragile offspring.

Only the adoption of Modern Genetic practices has salvaged the racehorse industry. With forceful encouragement from the gambling industry who saw the threat to their golden goose.

As for dogs, cats & other housepets? Many of the so-called breeds are less than two centuries in existence. Bred solely based on crude, external physical appearance & popularity. To appeal to ignorant buyers who wanted the latest status symbol or fashion statement.

For all those pet owners who will complain that I am exaggerating their lack of competency to choose their purchases?

Collect & total all the veterinarian bills you have paid or still owing over the years of owning pets.
Surveillance_Egg_Unit
1 / 5 (3) Oct 13, 2018
But what is the purpose in all this tomfoolery of unnatural procreation? Surely, these 'scientists' don't really think that two women can impregnate each other sexually. Nor can two males.


You dont know that, if this research progresses then maybe it will be possible in humans, too.
says shotman maslo

Well, we all know that some scientists are always trying the impossible. Perhaps they expect funding from those who perform unnatural sex on each other and would have much to gain from such experiments. It is still an abomination, even without biblical verses.

LOL You seem to be of the opinion that unnatural sexual procreation is the ultimate goal to look forward to from science. If it had been the best of all possible methods, it would have already been made a natural method millions of Earth years ago at the beginning of Evolution. But it hadn't, and there are good reasons for such an unnatural way to procreate to have been discarded by Nature.
Surveillance_Egg_Unit
1 / 5 (3) Oct 13, 2018
aegue, as trumpenella's offspring are notoriously sub-intelligent criminals. Maybe your belief in the anti-science of eugenics finds validity ib America's First Crime Family.

As for your inferiority-complex driven cowardice with women, coloreds and and anyone who doesn't need to use all their fingers and toes to count to twenty? It's way past time for you to grow a backbone.

All that ideological baggage of political correctness that burdens your shriveled soul? That's your problem to deal with. Or at least, come to terms with if you have any capacity for self-awareness.
says rrwilliejoe

R0FLMAO

= )
rrwillsj
1 / 5 (1) Oct 14, 2018
Oh, segue. I am pleased that you can finally comprehend what a dunderhead you have been all your life. And through humor, maybe what little is left of your humanity can be salvaged?
Surveillance_Egg_Unit
1 / 5 (2) Oct 14, 2018
Oh, segue. I am pleased that you can finally comprehend what a dunderhead you have been all your life. And through humor, maybe what little is left of your humanity can be salvaged?

says rrwilliejoe

Williejoe, the only humour that I find in this particular forum and in so many others, is in your comments. It is so hard to not be amused. There are others whom I find hilarious also when they make their stupid comments that make no sense, such as: your old friend, SpookyOtto and Captain Chickenshit and all of their sox; Ojorf is also amusing in a weird sort of way - only because he is an arse-kisser on the previous two.

My "humanity" rests only in my human host, who is extremely cooperative and has allowed me to use his human form for my purposes, for he too, sees the futility in the rest of mankind.
Salvaging mankind is not what we do. It is up to mankind to salvage themselves. We just remove what it was that made them make such evil choices.

So, williejoe, take care
Anonym518498
2.7 / 5 (3) Oct 14, 2018
Women want this stopped, they don't want mice or humans with 2 fathers, they want mice and humans with ZERO fathers, goal of the feminist movement
rrwillsj
1 / 5 (1) Oct 15, 2018
annoyingmousie, since you have evidently spent your entire life in hiding. Cowering away from any communication with females.

How would you know what any women, including feminists, might want.

Though I would guess they are pleased to have fortuitously avoided your inbred, defective genetic contribution.

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