Eggs from skin cells: a promising option for infertility?

BarcelonaThe inability of women to conceive began to be treated as a medical issue nearly two hundred years ago. However, it hasn't been until the last four decades that science has made a push to find solutions to infertility linked to age or caused by the side effects of treatments for certain diseases such as cancer. The World Health Organization (WHO) estimates that one in six people worldwide will experience this problem in their lifetime, and in the case of women, research has opened up promising avenues. One example is the study published this Tuesday in Nature Communications The team of American biologist Shoukhrat Mitalipov, a pioneer in reproductive research, has proven that, in the laboratory, human skin cells can be used to produce fertilizable eggs using an innovative technique.

Mitalipov's team at the Center for Embryonic Gene and Cell Therapy at Oregon Health & Science University in Portland specializes in somatic cell nuclear transfer, a technique that allows the nucleus of an adult cell to be reprogrammed to become another type of cell. Specifically, they introduced the nucleus of a person's skin cell into the egg of a donor whose nucleus had previously been removed. In other words, they performed a type of cellular reprogramming. What's more, the scientists have managed to induce an unprecedented response: a skin cell undergoing a nuclear division that normally only occurs in eggs and sperm.

Sexual gametes have 23 chromosomes, and this has a reproductive meaning, which is to ensure that when the egg and sperm fuse during fertilization, the resulting zygote has 46 chromosomes: 23 from the father and 23 from the mother. Since cells have 46 chromosomes, an egg created with this nucleus would have twice as many chromosomes as a normal gamete, which would prevent proper embryo development. To solve this problem and obtain a functional oocyte ready for fertilization, researchers devised a process that simulates natural egg division and eliminates excess chromosomes.

Thanks to this procedure, Mitalipov created 82 functional eggs, which were then fertilized with sperm in the laboratory. Approximately 9% of these fertilized eggs reached the blastocyst stage, the stage at which the embryo is ready to be implanted in a uterus. However, none were further cultured, as they must be implanted in a uterus after that point, and bioethical regulations prevent this. In any case, the study shows that the genetic material from skin cells can be used to generate an egg-like cell and, furthermore, that the chromosome number can be corrected for possible future fertilization.

"Exciting" proof of concept

Infertility affects millions of people worldwide—men and women in equal numbers—and is mostly caused by a dysfunction or absence of one of the two sex cells. In some cases, fertilization in vitro Conventional treatment can be ineffective, and this has led science to seek experimental treatments to propose solutions. In animal models, specifically mice, Japanese scientists have achieved goals such as producing eggs from non-reproductive stem cells or gestating a mouse with only sperm, which reached adulthood. However, in humans, a fully functional human oocyte has not yet been generated in the laboratory, since it is extremely complex to generate the real conditions of an ovary.

"This advance, called mitomyomeiosis, is an exciting proof of concept. Although it is still very early laboratory work, in the future it could transform the way we understand infertility and miscarriage, and perhaps one day open the door to the creation of similar cells as an option," says Ying Cheong, professor of reproductive medicine and honorary consultant in reproductive medicine and surgery at the University of Southampton.

The researchers admit that more research is currently needed to ensure the efficacy and safety of this technique before applying it to humans. Most of the embryos did not progress beyond fertilization, and some presented chromosomal abnormalities. "This study is of enormous importance, as it demonstrates that this process is potentially viable in human cells and opens the door to future research on this technique. However, more extensive research is necessary before considering its clinical application," Rocío Núñez Calonge, scientific director of the UR International Group and coordinator, agreed in a statement to SMC Spain.