Gene editing and stem cell research have provided alternative reproduction of rodents
Baby-making science has exceeded a new threshold, at least in rodents. A team of scientists in China has succeeded in creating a small number of apparently healthy mouse pups of female parents of the same sex. The researchers also produced offspring from two mouse fathers, but these puppies all died shortly after birth, underlining the fact that the new technique is still faced with serious obstacles.
The team's approach, based on stem cell science and CRISPR-Cas9 gene processing, is a "new way to produce offspring from same-sex mammals," says senior author Qi Zhou, who works on stem cells and reproductive biology at the Chinese Academy of Sciences.
If the process can be greatly improved and it works well with larger mammals, it can eventually offer hope to same-sex couples who want to have children who are biologically related to both parents. Yet that scenario remains far away and may not be scientifically feasible at all. "The amount of work needed to convince us that this will not do any harm to people is huge and is very important to us," says Fyodor Urnov, deputy director of the Altius Institute for Biomedical Sciences at Seattle, who is not involved. in the investigation. In addition, it would remain extremely controversial – partly because offspring of two women would have no Y chromosomes and thus could only be female.
Other researchers had previously derived offspring from two female mice, but the rodents developed various health problems and the process was more cumbersome, says Zhou. Scientists in the US had also previously produced offspring of two male mice, but that work used a completely different technique to create an intermediate & # 39; mother & # 39; that means that one of the fathers got the ability to form eggs. That two-paternal process would not apply to people (at least with current technologies) because it builds on a genetic anomaly that could cause human infertility, says Richard Behringer, a professor of genetics at the MD Anderson Cancer Center of the University of Texas the former two fathers work. The research by Zhou and colleagues, he says, is "a technical masterpiece." The team's findings were reported Thursday in a study published in Cell stem cell.
To get mice that were biologically related to two mothers, Zhou and his colleagues exposed immature eggs to chemicals that caused the eggs to behave as if they were fertilized and begin to divide. From those eggs, the scientists were then able to harvest stem cells that were haploid, meaning that each contained only half the typical number of chromosomes, instead of a complete set of two parents.
The researchers then "removed" the remaining instructions from the haploid stem cells to behave like eggs. They have achieved this by using CRISPR to remove three essential regions of DNA that determine which switches are switched on and off along the genome to express the genes of a specific parent (a phenomenon that is imprinting called). Then they had to coax the same cells to respond more to sperm, so they deleted other important DNA sequences that controlled which genes were switched on or off. The researchers then injected each artificial sperm cell into another egg, resulting in a bi-maternal embryo. Eventually the embryo was implanted in the womb of a third mouse that functioned as a surrogate mother. In this way, the team ended with 29 live mice of 210 embryos – a success rate of about 14 percent. These puppies grew up and got offspring of themselves, conceived by male mice.
Trying to produce mice with two fathers was even more complicated and much less successful. The first steps were similar: starting with reproductive cells (this time sperm) and using laboratory techniques to induce haploid stem cells. Then the researchers deleted seven DNA regions, regions that control the imprinting, from each of those cells. Then they injected each of those modified sperm stem cells – along with the semen of a second father – into a de-nucleated egg (the core of which had been removed, so it had no biological instructions of its own). For this two-headed system to work, they still needed a placenta, which feeds a fetus during pregnancy. So they then had to perform a difficult process to obtain placenta-forming material from a completely separate, non-viable embryo, and then incorporate that external contribution into the paternal embryo. Eventually that compressed embryo was implanted in a surrogate mother. Less than 2 percent of the mice made in this way were born alive and those who died shortly after birth.
"The rapid death of the offspring revealed that there were still a number of unknown reproductive / development barriers to cross during the production of bi-paternal mice," notes Baoyang Hu, a lead author of the new study, . "In nature bi-maternal reproduction – or parthenogenesis – is fairly common in vertebrates such as amphibians, reptiles and fish, but successful reproduction of two males is very rare and can only be found in specific fish under specific experimental conditions." means that the production of two-paternal mice "might have to bridge more barriers than the bi-maternal mice."
Yi Zhang, a professor of genetics at Harvard Medical School who was not involved in the work, says that the main benefit of these new findings lies in addressing some basic scientific questions, and in the way in which the scientific boundaries of reproduction and epigenetics test. "From a scientific point of view, this is very difficult even for mice," he says. "And for primates and people it will be 10 times harder."