from the how-do-you-like-your-eggs?-unfertilized dept.
In an advance that could lead to new fertility treatments, researchers have coaxed immature human egg cells to fully develop in the lab for the first time. Still unclear is whether the resulting eggs, which reached maturity in just 22 days, compared with 5 months in the body, are normal and whether they can combine with sperm to make a healthy embryo.
The feat nonetheless is "extraordinarily important," says Kyle Orwig, a stem cell biologist at the Magee-Womens Research Institute at the University of Pittsburgh in Pennsylvania who was not involved in the new work. "It has real potential for application," he adds. "We already have the patients."
Those patients include women who have gone through chemotherapy, which can damage eggs and cause infertility. Girls with cancer who haven't hit puberty don't yet produce mature eggs that can be frozen, so some choose to preserve a small piece of ovarian tissue, which can later be placed back in the body to start making eggs. But that's a risky choice in some cases, because the transplant could reintroduce the cancer with the cells. If the new process is perfected, these women could instead rely on the tissue they saved as girls to generate eggs for in vitro fertilization.
[...] In the new work, Telfer and her collaborators completed the whole developmental cycle. They took small samples from the ovaries of 10 women undergoing elective caesarian sections, and isolated 87 follicles, which they let develop in a soup of nutrients. Then came a new step: They carefully extracted the fragile, immature eggs and some surrounding cells from the follicles, and allowed them to further mature on a special membrane in the presence of more growth-supporting proteins. In the end, just nine of these eggs passed the final test for maturity [open, DOI: 10.1093/molehr/gay002] [DX]—they were able to divide and halve their chromosomes so they were ready to join with sperm during fertilization, the researchers reported online 30 January in Molecular Human Reproduction.
The next step would be to create the primordial follicles from stem cells or skin cells.
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Eggs can be 'tricked' into developing into an embryo without fertilisation, but the resulting embryos, called parthenogenotes, die after a few days because key developmental processes requiring input from sperm don't happen.
However, scientists from the Department of Biology & Biochemistry at the University of Bath have developed a method of injecting mouse parthenogenotes with sperm that allows them to become healthy baby mice with a success rate of up to 24 per cent. This compares to a rate of zero per cent for parthenogenotes or about two per cent for nuclear transfer cloning.
[...] The baby mice born as a result of the technique seem completely healthy, but their DNA started out with different epigenetic marks compared with normal fertilisation. This suggests that different epigenetic pathways can lead to the same developmental destination, something not previously shown.
The discovery has ethical implications for recent suggestions that human parthenogenotes could be used as a source of embryonic stem cells because they were considered inviable. It also hints that in the long-term future it could be possible to breed animals using non-egg cells and sperm. Although this is still only an idea, it could have potential future applications in human fertility treatment and for breeding endangered species.
Mice produced by mitotic reprogramming of sperm injected into haploid parthenogenotes (open, DOI: 10.1038/ncomms12676) (DX)
Scientists have coaxed mouse egg precursor cells, created from stem cells, into producing fertile egg cells. The egg cells were created in ovaries outside of a living mouse, but the "lab-based ovaries" were small cell clusters taken from existing fetal mouse ovaries:
In work that raises the prospect of new infertility treatments and designer babies, researchers have used stem cells to grow fertile mouse egg cells for the first time entirely in a lab dish. The eggs gave rise to pups after being fertilized and implanted into rodent foster mothers. The method—which sometimes produced defective eggs and had a success rate of less than 1%—won't be producing human egg cells any time soon, but the technique could help researchers identify key genes involved in egg development and maturation. The work is a "stunning achievement," says George Daley of Harvard Medical School in Boston, who was not involved in the project.
Egg cells are uniquely powerful, containing the instructions needed to start the development of a new organism. Deriving such cells in the lab has long been a goal for researchers who want study their development in more detail. It also raises a futuristic possibility: being able to make human eggs in the lab from skin or other donor cells—and even being able to make genetically altered egg cells. However, any application to human cells is a very long way off, says Katsuhiko Hayashi, a stem cell biologist at Kyoto University in Japan, who led the new mouse egg studies.
[...] The work published today combines the insights gained from that study with the earlier techniques for turning ES and iPS cells into egg precursor cells. First, the scientists used ES and iPS cells to make immature egg precursor cells. Then they inserted those precursors into clusters of cells taken from fetal mouse ovaries. They carefully cultured those cell clusters for more than a month. [emphasis mine]
The team's lab-based ovaries produced more than 50 mature egg cells each, the scientists report. The labmade eggs had higher rates of chromosome abnormalities than is usually observed in eggs in normal mouse ovaries, but more than 75% had the correct number of chromosomes. The scientists mixed some of those eggs with mouse sperm, producing more than 300 two-cell embryos, which researchers then implanted into foster mothers. However, only 11 of those embryos—or 3%—grew into full-term pups, compared with 62% for eggs taken from adult mice and fertilized in vitro. The reasons for that are still unclear, Hayashi says. The pups that did survive grew into apparently healthy, fertile adults. The researchers also showed that they could derive new ES cell lines from embryos generated from the labmade eggs. That recreates, they note, a full cycle of female germ cell development in the lab.
If scientists can develop suitable lab-grown ovaries and artificial wombs, it won't matter if the success rate is in the single digits (and the technique will probably be improved over time), and human embryos could be grown as desired without requiring human participants. There would be no need to "exclude a risk of having a baby with a serious disease" as one of the authors warns, if the purpose is experimentation rather than fertility treatment.
Reconstitution in vitro of the entire cycle of the mouse female germ line (DOI: 10.1038/nature20104) (DX)