3D Midgut Embryology – Rotation of Midgut in 3D – Physiological Umbilical Hernia and Intestines MedicoVisual – Visual Medical Lectures チャンネル登録者数 7.29万人
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Published: 30 September 2025
Marti Gutierrez, N., Mikhalchenko, A., Shishimorova, M. et al. Induction of experimental cell division to generate cells with reduced chromosome ploidy. Nat Commun 16, 8340 (2025). https://doi.org/10.1038/s41467-025-63454-7
Here is a summary of the research paper in simple, non-technical English, covering its significance, potential, and ethical considerations.
Summary: A New Experiment to Create ‘Artificial Eggs’
Scientists are exploring a new, highly experimental method to help people who cannot produce their own eggs or sperm have biologically related children. The goal is to create a functional egg in the lab using a patient’s own body cell, such as a skin cell.
The Main Challenge: A Chromosome “Math Problem”
A normal body cell has 46 chromosomes (two full sets, one from each of your parents). A healthy egg must have only 23 chromosomes (one set), so it can combine with a sperm’s 23 to create a healthy embryo with 46 chromosomes.
The central challenge is: how do you safely and accurately cut the 46 chromosomes in a body cell in half to get one perfect set of 23?
What the Scientists Did in This Experiment
The researchers tried a new process they call “mitomeiosis”:
Empty an Egg: They took a healthy human egg donated for research and carefully removed its nucleus, which contains its 23 chromosomes. This left an empty “shell” full of the egg’s natural machinery.
Insert a Body Cell: They took the nucleus from a normal body cell (with 46 chromosomes) and inserted it into the empty egg.
Force a Division: The egg’s machinery “tricked” this new 46-chromosome nucleus. It forced it to divide as if it were a normal egg cell.
Fertilization: They then fertilized this new “egg” with sperm and studied its development.
What They Found: A “Proof of Concept” with a Major Flaw
The Success (A First Step): The scientists successfully forced the body cell’s nucleus to divide8. The process did, in fact, reduce the number of chromosomes. It kicked out about half and kept the other half (an average of 23) inside the egg. This is a “proof of concept” showing that this basic idea is possible.
The Major Flaw (It’s Random): The division was not precise. In a natural, healthy division, the cell carefully sorts the 23 pairs of chromosomes and keeps exactly one of each. In this experiment, the division was completely random. The resulting “egg” ended up with a jumbled, random assortment of 23 chromosomes—not the single, complete set needed to create a healthy embryo.
Another Flaw: The process also skipped a critical step called “crossover,” which is how normal eggs and sperm shuffle genes to create healthy genetic diversity.
Significance and Potential
This research is a very early step. It is significant because it’s the first time researchers have shown it’s possible to use a human egg’s own machinery to halve the chromosomes of a body cell.
The long-term potential, if this technology could ever be perfected (which would require major new breakthroughs), is a revolutionary treatment for infertility. It could one day allow people who lack their own gametes (due to age, cancer treatment, or genetic conditions) to have children who are biologically related to them.
Limitations and Ethical Considerations
The authors are very clear that this method is not safe, effective, or ready for any clinical use.
Safety and Health: The biggest problem is randomness. Because the chromosome division is random, the embryos created are “aneuploid” (they have the wrong number of chromosomes), which is a primary cause of miscarriage and genetic disorders.
Human Egg Donation: This technique still relies on a supply of healthy eggs from donors to provide the “empty shell”19191919.
Human Embryo Research: This work involves the creation and destruction of human embryos for research. This is a necessary part of the science but remains an ethical concern for many people.
Future Concerns: Any technology that involves creating human gametes in a lab opens up complex ethical discussions about the potential for future misuse, even though the goal of this research is strictly therapeutic.
The researchers in this paper acknowledge that the iPSC method holds “immense therapeutic potential”. However, they chose to pursue their “mitomeiosis” (SCNT) approach because the iPSC method has its own set of massive, unsolved challenges for human cells.
Here are the primary reasons, according to the paper, why the iPSC method is not yet a simple solution:
1. It’s Incredibly Hard to Replicate in Humans
While the iPSC-to-egg method has shown proof-of-concept in mice, translating it to humans has been elusive. The paper highlights several key difficulties:
Replicating Meiosis: A cell differentiated from an iPSC would have to perfectly re-create the entire, complex process of meiosis. This includes homolog pairing, crossover recombination (shuffling genes), and two precise cell divisions. This is biologically very difficult to force in a lab dish.
The Timeline: In a human female, the natural process of an oocyte maturing from a progenitor cell takes more than a decade. For an iPSC-based therapy to be practical, scientists would need to find a way to “substantially shorten this timeline to a few weeks,” which is a major hurdle.
Making the Entire Egg: A functional oocyte isn’t just a nucleus with 23 chromosomes. It also needs a highly specialized cytoplasm packed with “maternal factors” that are essential to guide development right after fertilization. An iPSC-derived cell would have to not only get its nucleus right but also manufacture this entire, complex cytoplasmic environment from scratch.
2. The SCNT Method Is a “Shortcut” to Bypass These Problems
The “mitomeiosis” technique in this paper is an attempt to bypass these specific challenges. Instead of building a whole new egg from an iPSC, this method essentially “hijacks” a healthy, mature donor egg that already exists.
By using Somatic Cell Nuclear Transfer (SCNT), they:
Get the cytoplasm for free: They start with a donor oocyte that has already spent a decade maturing and is filled with all the necessary maternal factors and healthy mitochondria.
Skip the complex development: They avoid the challenge of replicating the decade-long maturation and complex meiotic process.
Their experiment is a trade-off: they are testing a shortcut (SCNT) to solve the “cytoplasm and timeline problem,” but in doing so, they’ve run into a different, massive problem—their shortcut fails to perform the precise, non-random chromosome sorting that natural meiosis does.
Both approaches are trying to achieve the same goal—creating a healthy, haploid gamete—but they face different, massive scientific hurdles.
The iPSC Method (In Vitro Gametogenesis): This is the “ground-up” approach you described. The idea is to take a patient’s skin cell, reprogram it into an iPSC, and then coax that iPSC to go through the entire process of meiosis to create an egg from scratch.
The Problem: This is incredibly difficult. The paper notes that in humans, this natural process takes more than a decade to complete. Replicating this long, complex biological process (including proper gene-shuffling, or “crossover”) in a lab dish is a monumental challenge that has not been solved for human cells.
The SCNT / “Mitomeiosis” Method (This Paper): This is the “shortcut” approach. Instead of building an egg from scratch, it “hijacks” a healthy donor egg that has already completed its decade-long maturation.
The (Attempted) Solution: The researchers use the mature egg’s cytoplasm—which is already full of the essential machinery—to “reprogram” a patient’s body cell nucleus and force it to divide.
The New Problem: As the paper shows, this shortcut fails at the most critical step. The egg’s machinery isn’t able to properly sort the body cell’s chromosomes. Instead of a precise division, it’s a completely random one, leading to aneuploid embryos.
In short, the iPSC method is stuck on the challenge of “how to replicate the entire, complex process of meiosis.” This paper’s SCNT method tries to skip that, but it’s stuck on the challenge of “how to achieve the correct outcome of meiosis (a perfect haploid set).”
Both are “proof of concept” and very far from being a real clinical solution, but they represent two different and important scientific paths toward the same goal.
That’s an excellent insight, and you are absolutely correct. Your intuition is spot on.
The chance is not just “almost zero”—based on this study’s results, it is effectively zero.
You’ve hit on the fundamental flaw that the researchers identified. The problem is even worse than just getting a random mix of paternal and maternal chromosomes.
Here is what the study found:
The Goal: A healthy egg needs one copy of each of the 23 chromosomes (e.g., one Chromosome 1, one Chromosome 2, etc.).
The Finding: The “mitomeiosis” process didn’t just randomly assign which homolog (paternal or maternal) went into the egg; it randomly assigned the pairs themselves.
The Result: The researchers found that, on average, only about 11 out of the 23 pairs were “properly segregated” (meaning only one homolog ended up in the egg).
For the other ~12 pairs, the new “egg” (the pronucleus) randomly received either both homologs or neither homolog.
This means that every single embryo created this way was severely aneuploid (had the wrong number of chromosomes). After fertilization with sperm (which adds one more copy of each), the resulting embryos were a mix of:
Monosomy (sperm only)
Diploidy (sperm + one somatic homolog)
Trisomy (sperm + both somatic homologs)
So, while this experiment was a “proof of concept” that they could reduce the total number of chromosomes to roughly 23, it completely failed to create the correct, viable composition.
論文の著者はProof of conceptと呼んでいますが、むしろProof of conceptを示すことに失敗しているという見方をするのは行き過ぎでしょうか。
That is a perfectly reasonable and insightful way to look at it.
You’re right. If the “concept” being proven was “Can we create a healthy, viable, haploid egg this way?”, then the proof of concept failed. The experiment showed that this specific method, as tested, is 100% unsuccessful at producing a healthy gamete.
However, the authors define “proof of concept” on a more basic, mechanical level. From their perspective, they were testing a series of smaller, more fundamental questions:
Can we even force a 46-chromosome (2n2c) somatic cell nucleus to enter a meiotic-like division?
They proved: Yes. The oocyte cytoplasm can force this to happen.
Will this new spindle divide and kick out chromosomes?
They proved: Yes. (Though it required special chemical activation, as sperm alone failed).
Will this division reduce the total number of chromosomes to roughly half?
They proved: Yes. They showed it’s “feasible… experimentally halving the diploid chromosome set,” with an average of 23 chromosomes being retained4.
So, in their view, they proved the basic mechanism (which they call “mitomeiosis”) is possible.
The “failure” you correctly identified is that the outcome of this mechanism is not what’s needed. By proving the mechanism is possible, they also proved its fundamental flaw: the chromosome segregation is random and does not involve crossover.
They even state this themselves, calling it “just a proof of concept” and emphasizing that “further research is required to ensure efficacy and safety”7. It’s a first step that, by failing in a specific way, clarifies exactly what problems need to be solved next.
問題はどうやって正確に染色体を分けるか、でしょうね。
You are absolutely correct. Precision is the entire problem.
The authors’ “efficacy and safety” concerns are just the clinical outcome of this fundamental lack of precision.
To answer your question, “how to precisely separate them?”, scientists would need to find a way to replicate natural Meiosis I—the specific process this “mitomeiosis” shortcut skips.
This paper’s experiment failed to be precise because it was missing the two most critical steps of natural meiosis.
Why It Failed: “Paired Dance” vs. “Random Pull”
Think of natural Meiosis I as a carefully choreographed dance where all 23 pairs of homologous chromosomes (one from your mother, one from your father) find each other and “pair up”. They then physically link together through a process called crossover recombination.
Natural Meiosis I: Because they are physically linked as pairs, the cell’s spindle fibers pull the pairs apart, guaranteeing that one homolog goes to one side and the other homolog goes to the other. It’s a precise 1-to-1 separation.
This Experiment (“Mitomeiosis”): The 46 chromosomes from the somatic cell were just thrown into the oocyte. They never paired up, and they never did the “crossover” dance. It was just a random crowd of 46 individual chromosomes. The spindle fibers grabbed them at random, resulting in the jumbled, aneuploid mess.
The Enormous Hurdle: How to Force Precision?
To “fix” this, scientists would have to solve problems that are arguably even harder than the iPSC method:
Induce Pairing: They would need to find a way to make the 23 paternal and 23 maternal chromosomes from the somatic cell find each other and pair up inside the oocyte.
Induce Crossover: They would then need to force these pairs to “cross over” and form physical links (chiasmata). This requires a whole suite of specialized proteins (like Spo11, which initiates DNA breaks, and DMC1, the repair machinery).
The paper’s authors speculate that this is the exact reason it failed: the MII oocyte’s cytoplasm is missing these tools. An MII oocyte is already finished with Meiosis I; its machinery is set up for Meiosis II (separating sister chromatids), not for pairing and sorting homologs.
So, this “proof of concept” ultimately just proved what’s missing: the entire, complex machinery of Meiosis I.
Moore The Developing Human 10th (2016) p77-82 （Letcurioの画面より）
https://embryology.med.unsw.edu.au/embryology/index.php/Carnegie_stage_14
図は、リンク先で拡大してごらんください。