The genetic identity of human egg cells can be changed in the lab
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Recent advancements in genetic research have led to the development of human embryos using eggs that have been genetically altered to incorporate DNA from adult skin cells. This innovative breakthrough, previously demonstrated in mice, opens up possibilities for same-sex couples or women experiencing fertility challenges to conceive children who share genetic materials from both parents.
While cloning techniques in animals have long been established, the desire among many couples to produce offspring with a combination of both partners’ genetic contributions necessitates the involvement of both sperm and eggs. As noted by Shoukhrat Mitalipov from Oregon Health and Science University, achieving this requires overcoming the challenge presented by eggs and sperm being haploid, each containing only a single set of chromosomes, as opposed to the usual double set found in other cells.
In natural development, female embryos form all of their eggs while still in the womb, wherein the progenitors of these egg cells undergo a complex sequence of duplication, blending, and division to reduce their count from 46 chromosomes to 23. Mitalipov theorized that this intricate process could be replicated in vitro by harnessing the natural biochemical signals that facilitate chromosomal division during the maturation of human eggs.
Following successful trials in mice, Mitalipov and his team embarked on human trials. Initially, they removed the nuclei from multiple eggs donated by healthy women, which had been precisely halted at a developmental stage conducive to chromosomal separation. Next, they introduced nuclei from fibroblast skin cells of a healthy female donor into these eggs. Microscopic observations showed that the chromosomes were aligning along spindles, the scaffold structures aiding in their segregation.
Subsequently, sperm from a healthy donor were injected into some of these eggs. This technique mirrors that used in procedures involving mitochondria from a third party, which helps mitigate the risk of certain genetic disorders in offspring. Normally, sperm injection catalyzes the finalization of the egg’s chromosomal selection process, enabling the disposal of duplicate DNA, thus preparing the egg for the infusion of genetic material provided by the sperm. However, in the skin-derived eggs utilized in this research, this separation was impeded, leading to integrations where chromosomes aligned but failed to complete their division.
To overcome this hurdle, the researchers conducted additional experiments that included applying electrical stimuli to the eggs, fostering calcium influx akin to the natural biological signals triggered upon sperm contact. Coupled with incubation using a drug that activated the eggs’ dormant state, the research team was finally able to promote successful chromosomal halving within the eggs. In their final results, approximately 9% of the fertilized eggs developed into blastocysts, the cell clusters typically prepared for implantation during in vitro fertilization (IVF). However, the team did not pursue the transfer of these blastocysts or maintain them beyond the six-day developmental mark.
Despite the progress, the genetic blend of remaining chromosomes displayed a tendency toward anomalies. Mitinori Saitou from Kyoto University expressed caution, asserting that the method remains unsuitable for clinical application at this present stage. Similarly, Katsuhiko Hayashi from the University of Osaka acknowledged the sophistication of the approach while deeming it inefficient and risky for immediate implementation. Yet, he recognized the breakthrough in achieving successful chromosome halving in human cells, suggesting that future advancements in technology may emerge from this foundational work.
Mitalipov reaffirmed the validity of the criticisms, noting that his team is focused on addressing the defect issues. “The bottom line is that we’re kind of halfway there, but still not exactly where we need to be,” he commented.
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