Same-sex mice have babies By James Gallagher Health and science correspondent, BBC News Published 11 October 2018 image copyright Leyun Wang image caption This adult mouse has two mums and no dad, was healthy and able to have healthy pups of her own Baby mice have been made with two mums and no dad, say researchers at the Chinese Academy of Sciences. It took a substantial feat of genetic engineering to break the rules of reproduction. The scientists said the "bimaternal" (two mammas) animals were healthy and went on to have pups of their own. But there was bad news on the all-male front. Mice with double-dads were attempted, but died within days of being born. Why even try? The researchers were trying to answer fundamental questions about why we have sex. Mammals, including us, can make babies only through sexual reproduction - aka you need an egg from mum and a sperm from dad. But the rest of the natural world doesn't play by the same rules; some female fish, reptiles, amphibians and birds can go it alone. Welcome to the bizarre world of virgin births known officially as parthenogenesis. image copyright Getty Images image caption The Komodo dragon is one of many species able to reproduce through parthenogenesis The aim of the Chinese researchers was to work out which rules of reproduction they needed to break to make baby mice from same-sex parents. That in turn helps understand why the rules are so important. "It's an interesting paper... they're trying to work out what you would have to do to turn us into turkeys," said Prof Robin Lovell-Badge at the Francis Crick Institute. (Yes, your Christmas dinner can reproduce without having sex too.) Go on then, how did they do it? In short, with a lot of cutting-edge science. It was easier with double mums. The researchers took an egg from one mouse and a special type of cell - a haploid embryonic stem cell - from another. Both contained only half the required genetic instructions or DNA, but just bringing them together wasn't enough. The researchers had to use a technology called gene editing to delete three sets of genetic instructions to make them compatible (more on that later). The double-dad approach was slightly more complicated. It took a sperm, a male haploid embryonic stem cell, an egg that had all of its own genetic information removed and the deletion of seven genes to make it all work. image copyright Leyun Wang image caption The double dad, or bipaternal, mice died within 48 hours of being born So they broke the rules, what did they learn? The reason we need to have sex is because our DNA - our genetic code - behaves differently depending on whether it comes from mum or dad, the study in Cell Stem Cell suggests. And without a female copy and a male copy our whole development gets thrown out of whack. It's called genomic imprinting with parts of the DNA in sperm and parts of the DNA in eggs getting different "stamps" that alter how they work. Errors in genomic imprinting have been implicated in some diseases such as Angelman syndrome. The bits of DNA carrying these stamps were the ones the researchers had to delete in order to make the baby mice viable. Dr Wei Li, who conducted the experiments, said: "This research shows us what's possible. "We saw that the defects in bimaternal mice can be eliminated and that bipaternal reproduction barriers in mammals can also be crossed." So can I have a baby with my same-sex partner? Unless you're a mouse reading this, and a female one at that, then the answer is not any time soon. Dr Teresa Holm, from the University of Auckland, thinks there is a chance in the long run. "[The research] may even lead to the development of ways for same-sex couples to reproduce healthy children of their own," she says. But she points out there are "significant ethical and safety concerns that would need to be overcome". It would not be allowed to happen until scientists could be sure any resultant children would grow up mentally and physically normal. Some people have doubts that the mice were completely OK. Dr Lovell-Badge told the BBC: "Even with two mothers I'm not convinced they're normal and the success rate is pretty low. "It is not something I'd hope anyone would contemplate." So is sex about to disappear? "Not yet, no," he says. Follow James on Twitter. More on this story Virgin-born sawfish found in Florida Published 1 June 2015 'Virgin births' for giant lizards Published 20 December 2006<doc-sep>Healthy mice with two mothers have been born for the first time in a study that pushes the boundaries of reproductive science. Mice with two fathers were also born, but only survived a couple of days, the Chinese team behind the work reported. There is no imminent prospect of the techniques being used clinically in people, but the findings demonstrate that the biological barriers to same-sex reproduction can, technically, be overcome. “This shows us what’s possible,” said Wei Li, of the Chinese Academy of Sciences and a senior author of the paper. Scientists have previously managed to produce baby mice with same-sex parents, but the offspring had serious abnormalities and the methods used often required convoluted sequences of genetic manipulations, sometimes involving several generations of mice. The work explores a long-standing question in biology: that of why in mammals, equal genetic contributions from both a mother and a father are necessary. Elsewhere in the animal kingdom – in hammerhead sharks and komodo dragons, for instance – no genetic contribution from a father is required. A major barrier in mammals is a phenomenon known as “imprinting”, where for 100 or so genes only the copy that came from the mother or only the copy that came from the father are ever switched on. In the genome, maternal and paternal contributions are all jumbled together but these genes carry a chemical tag, labelling which parent the gene originated from in the first place. Without the right pattern of male and female imprinting, a viable embryo cannot be produced. The latest paper demonstrates how this apparent barrier could be overcome. For the mice with two mothers, the scientists started off with embryonic stem cells from a female mouse. Using the gene-editing tool Crispr-Cas9, they were able to remove maternal imprinting from three crucial regions of DNA by snipping out a single letter of the genetic code where the chemical tag was attached. This effectively made the genetic material appear more “male” in terms of its imprinting pattern. When the modified stem cells were injected into the unfertilised egg of a second female mouse, the genetic material from the two female mice combined to form an embryo. They produced 29 live mice from 210 embryos. The mice were normal, lived to adulthood and had babies of their own. Q&A What is Crispr? Show Crispr, or to give it its full name, Crispr-Cas9, allows scientists to precisely target and edit pieces of the genome. Crispr is a guide molecule made of RNA, that allows a specific site of interest on the DNA double helix to be targeted. The RNA molecule is attached to a bacterial enzyme called Cas9 that works like a pair of 'molecular scissors' to cut the DNA at the exact point required. This allows scientists to cut, paste and delete individual letters of genetic code. In October 2020, Emmanuelle Charpentier and Jennifer A Doudna were awarded the Nobel chemistry prize for their work on it – the first time that two women have shared the prize. Was this helpful? Thank you for your feedback. A similar experiment was performed using sperm and genetically modified stem cells from a male mouse, which were injected into a female egg that had been stripped of its own genetic material. These embryos were transferred to surrogate mothers, who carried them to term. But the pups only survived 48 hours after birth. There is good evidence that imprinting plays a similar role in human reproduction, although involving some different genes. However, there is no prospect of this strategy being applied in the clinic as there would be serious concerns about the side-effects of modifying genes which are known to be crucial for basic development. “It is unthinkable to generate a human baby that way,” said Christophe Galichet, senior scientist, at The Francis Crick Institute in London. “The authors have made an extremely important step forward in understanding why mammals can only reproduce sexually,” he added. Prof Azim Surani, director of germline and epigenomics research at the Gurdon Institute, University of Cambridge, said: “The comprehensive nature of the manipulations involved rules out – at least for now – any such attempts to generate bi-maternal human embryos. The bi-paternal embryos in this experiment, in any case, did not survive for long”.<doc-sep>
Scientists have been able to breed mice with same-sex parents using a breakthrough technique involving stem cells and gene editing. Researchers at the Chinese Academy of Sciences have produced healthy mice with two mothers, who were then able to go on to reproduce themselves. Mice with two fathers were also born during the study, but only survived for a matter of hours. Using female same-sex parents, the scientists were able to produce a total of 29 live mice from 210 embryos. All these offspring were normal, lived to adulthood, and were able to give birth to offspring of their own. The study, published in scientific journal Cell Stem Cell, examined why same-sex mammals are not typically able to reproduce, suggesting stem cells and targeted gene editing can make the process easier. “We were interested in the question of why mammals can only undergo sexual reproduction,” the study’s co-senior author Dr Qi Zhou said. “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 embryonic stem cells with gene deletions.” While some species of reptiles, amphibians and fish can change gender in order to reproduce or exist as both male and female at the same time, same-sex reproduction for mammals is a more difficult proposition, Dr Zhou said. He said in mammals, certain maternal or paternal genes are shut off during the development of sperm and egg cells, meaning offspring that do not receive genetic material from both a mother and father might experience developmental abnormalities. Almost 30 healthy babies were produced by same-sex mice parents during the study (SWNS) By deleting imprinted genes from immature eggs, researchers have in the past been able to produce mice with two mothers, although most still displayed genetic defects. To produce healthy bi-maternal mice, Dr Zhou, his co-senior authors Dr Baoyang Hu and Dr Wei Li, and their colleagues used haploid embryonic stem cells (ESCs), containing half the normal number of chromosomes and DNA from each parent. “We found in this study that haploid ESCs were more similar to primordial germ cells, the precursors of eggs and sperm,” Dr Hu said. “The genomic imprinting that's found in gametes was ‘erased’.” Alongside the 29 healthy mice produced by same-sex female parents, a dozen mice were also born to two male parents during the course of the study. ✕ US: Device allows scientists to control the BRAINS of mice However, the process of creating mice from same-sex male parents, which involves modifying a larger amounts of genes and inserting fertilised embryos into surrogate mothers, is more complicated. All offspring from two males born during the study died after less than 48 hours, although scientists believe they can improve the process in future tests. “This research shows us what's possible,” Dr Li said. “We saw that the defects in bi-maternal mice can be eliminated and that bi-paternal 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 mice with same-sex parents, which are also interesting for studying genomic imprinting and animal cloning.” Additional reporting by agencies