Imagine a future in which the infertility caused by the lack of ovules or sperm is no longer an insurmountable obstacle. A future where two men can have a biological child together, or where A woman who has lost her ability to produce ovules For age or for a cancer treatment may have offspring with its own genetics. This future, which until now belonged to science fiction, is a little closer thanks to a revolutionary advance that has been published in Nature. Biology This advance, which seems like a science fiction, has been made by the team of researchers at Oregon Health & Science University, led by Dr. Shoukhrat Mitalipov. In this case they have managed to develop an experimental technique that forces a skin cell (somatic) to reduce your number of chromosomes in half. It is, in essence, the most crucial and complicated step in the creation of a gamete (an ovule or a sperm). A process they have called mitomeiosis. To be able to understand it, you have to know that all the cells of our body have in total 46 chromosomes in its nucleus. But there is an exception: sperm and gametes that They have 23 chromosomes. A very important number so that when an ovule and sperm merge, they have a total of 46 chromosomes. That is why it is revolutionary that they have managed to get a skin cell to have 23 chromosomes to be an ideal candidate to give offspring. The trick. The natural process to create these haploid cells (with 23 chromosomes) is called meiosis. A very complex type of cell division that has been investigating for a long time. This made it replicate in a laboratory, which is known as in vitro gametogenesis (IVG) was one of the greatest challenges of biology. Something that now reminds us of what we already saw with the Dolly sheep in the cloning process. OHSU’s team addressed the problem in an ingenious way. Using a technique similar to cloning, called nuclear somatic cell transfer (SCNT). A technique that is complex, but can be summarized in three different steps: The first thing is to take a donated human ovule and extract the genetic material. In this way, the ovule maintained all its cytoplasm with the organelles, which ultimately is like the machinery that the cell has to produce energy and carry out many processes such as meiosis. Once done, a skin cell is taken (a diploid cell with 46 chromosomes in a 2N state) and is extracted the nucleus inside. Now it only remains to introduce the core of the skin cell into the ovule that has been emptied. The result. In this case it was amazing, since the ovule cytoplasm could ‘deceive’ the skin’s core, forcing it prematurely into a state similar to the metaphase of the Meiosis. This caused its 46 chromosomes to be organized in a spindle ready to divide, despite having skipped the DNA duplication phase in the cell cycle that is before the division of the genetic material. The problem. However, here they met a wall. In nature, the entrance of the ‘active’ sperm to complete its division, being mediated by a large number of zinc. But in this case, when they tried to fertilize the SCNT ovules with sperm, the vast majority (almost 77%) remained ‘arrested’ without reacting. The natural signal was not enough for this artificial construction. The solution in this case went to develop an artificial ‘starter’ key. After sperm fertilization, they applied an assisted activation protocol an electrical pulse by electroporation to simulate the calcium entry caused by sperm to its entrance, followed by a treatment with a chemical inhibitor called Roscovitin. And it is something that ended up working. Forced activation made the modified ovules leave their arrest and complete the division. The 46 chromosomes of the cell were separated, leaving an average of 23 chromosomes within the fertilized ovum (now a zigoto) and expelling a small polar body from the rest, having achieved the long -awaited ploidy reduction that was the objective of this experiment. Progress. The embryos resulting from this experiment containing chromosomes of the skin and sperm cell, beginning to divide and even some reached the blastocyst phase (an early development of about 5-6 days), with a success rate of 8.8%. This shows that genomes can integrate and work together. It’s just a test. The authors who are still a long way forward, since for now it is a “proof of concept” by not being a perfect replica of natural meiosis. In this case, segregation is random unlike meiosis, where it is ensured that each daughter cell receives a copy of each of the 23 types of original chromosomes. In this project the separation of homologous chromosomes (the paternal and maternal) was completely random. This generates aneuploid embryos that are incompatible with life. In addition, it also lacks ‘cross -rise’ or crossovera vital mechanism in meiosis where paternal and maternal chromosomes exchange fragments creating genetic diversity. This is something that is not present in this process and that takes away a lot of variability. The future. Despite the limitations of this study, work is a fundamental milestone. It aligns with other laboratories such as the Japanese Katsuhiko Hayashi that in 2023 managed to create functional ovules From male mice skin cells, with which healthy offspring were born. In the long term, the implications of these studies give hope to those women who suffer from infertility due to lack of functional gametes and who want to have offspring with their own genetics. The same happens in same -sex couples that also open the door for a couple of men (using a skin cell to create an ovule) or women (creating sperm) can have biologically related son between both members of the couple. Although we cannot also forget that right now there is a fertility crisis that causes that in Spain, for example, there is reduced birth rate. This is also conditioned that it is … Read more
