Altering this cloning technique could be game changer in fertility treatments

Scientists have created fertilizable human eggs by using material extracted from skin cells and a new technique called mitomeiosis. The newly developed method, the first of it’s kind, may open the door to new ways to help treat female infertility.“This technology would help treat age-related female infertility, or women with premature ovarian insufficiency for other reasons. It would also allow same-sex couples to have a child who is genetically related to both partners,” said Dr. Paula Amato, a professor of obstetrics and gynaecology at Oregon Health and Science University.In a paper she coauthored in Nature Communications, the researchers described using an approach that is a variation on cloning: somatic cell nuclear transfer (SCNT). But they incorporated mitomeiosis which leads to a result that is not a clone.SCNT is an established approach for creating clones used in regenerative medicine research, and in some parts of the agricultural industry. The first cloned animal, Dolly the sheep, was presented to the world in 1996. SCNT is used to create an embryo by taking an egg, removing its nucleus, and replacing that nucleus with one extracted from a somatic cell, such as a skin cell. Normally this results in a clone having only the genes and chromosomes from the skin cell, or whatever other somatic cell is used.Thus far, the technique could only be used to create clones because it results in a diploid genome, meaning it has 46 chromosomes—the same number of chromosomes from the somatic cell. But when it comes to non-clone human reproduction, one wants only half the cells: 23 from the somatic cell, and the other 23 from the oocyte or another cell. In other words, chromosomes from both parents. And this was the key point of the study: finding a way to reduce the number of chromosomes in the somatic cell nucleus once it’s inserted into a de-nucleated egg. The idea it to leave the correct number of chromosomes that can lead to reproduction once chromosomes from the other parent are also inserted into the egg.Where mitomeiosos comes inMitomeiosis is a form “of ‘reductive’ cell division. In other words, the SCNT egg, which contains a diploid number of chromosomes, ‘divides’ and in doing so extrudes half of its chromosomes into a polar body structure before combining with the chromosomes from the sperm to become diploid again,” Dr. Amato said.It is a multi-step procedure which includes use of an electrical pulse and an experimental drug, a CDK inhibitor, to trigger the nucleus in the egg to shed half of its chromosomes. After trying the technique in a series of mouse studies, the team studied the approach in human donor eggs where the oocyte nucleus was replaced by that from a skin cell. In brief, the technique successfully reduced the number of chromosomes in most of the samples, but not always by the right number. In the end, they produced 82 functional eggs. Still, it is a proof-of-concept with potentially major implications.“This work in humans is very preliminary and represents an incremental advance. It will likely take many years for IVG to reach the clinic,” Dr. Amato told the Canadian Healthcare Network.IVG, or in vitro gametogenesis is a technique whereby oocytes are created from stem cells. This new research can advance work in IVG.Earlier this year, Canadian obstetrical researcher Dr. Robert Casper published a review of what he called moonshot research. It highlighted work that contributed to transformative advances in reproductive, endocrinology, and infertility. While it was a review of advances in the past and did not include this new work on mitomeiosis, when asked about this new project, he told CHN that this work fits the bill. “This paper is definitely a breakthrough and will move the whole field of creating oocytes from somatic cells forward. Definitely a ‘moonshot’.” Dr. Casper is a professor emeritus of reproductive sciences at the University of Toronto.He explained in an email that “Creating oocytes from stem cells has been previously done but the oocyte cells formed in this way have 2N (46) chromosomes (diploid) the same as somatic cells. In order to be fertilized normally, the oocytes have to get rid of 23 chromosomes to become haploid and then when fertilized by a sperm cell (also haploid) the subsequent fertilized oocyte (called a zygote) is diploid with 46 chromosomes.”He noted that the process of oocyte maturation, or haploidization, prior to fertilization has been a problem. But the researchers managed to figure out how to use mitomeiosis to create haploid oocytes that are capable of being fertilized normally. “Even so, another technique was required to activate the oocyte so that fertilization could continue to form a zygote with a nucleus from the somatic cell chromosomes and a polar body containing 23 somatic cell chromatids. The subsequent embryos seemed to develop normally from that point onwards but it is unknown if these embryos can implant and form normal babies,” he said.

Altering this cloning technique could be game changer in fertility treatments

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