Scientists have demonstrated, using cutting-edge methods, the development of human embryos from somatic cells that could revolutionize fertility treatments for individuals lacking viable gametes. Mitomeiosis, in conjunction with somatic cell nuclear transfer (SCNT) in early embryos, is able to split the diploid chromosome set of human somatic cells in half and fuse them with chromosomes from sperm.
Most individuals globally suffer from infertility due to a lack of viable gametes. Age-related factors in women over their mid-thirties are one of the main causes that decrease oocyte quantity and quality. In vitro fertilization (IVF) provides no remedy for patients without functional eggs other than using donor gametes. Converting somatic cells into functional gametes, also known as in vitro gametogenesis (IVG), has become an increasingly effective approach in recent years. However, from mice to humans, it has proven extremely challenging to apply this technique to humans.
Researchers focused on SCNT, transplanting a somatic cell’s nucleus into an enucleated oocyte. By utilizing the cytoplasm of the donor oocyte, which contains vital maternal factors and mitochondria essential for totipotency, SCNT enables the direct reprogramming of the somatic genome into an oocyte-like state. Due to the possibility of triploidy, SCNT oocytes typically remain diploid, which prevents fertilization. Mitomeiosis causes non-replicated somatic genomes (2n2c) to enter metaphase rapidly after being transplanted into enucleated metaphase II (MII) human oocytes.
According to initial investigations, researchers suggested that activation failure was due to SCNT oocytes stopping at metaphase after fertilization. Next, the researchers applied electroporation in conjunction with roscovitine, a selective cyclin-dependent kinase inhibitor, for artificial activation. Somatic chromosomes were able to segregate into a polar body and a zygotic pronucleus, thereby preventing metaphase arrest. The experimental halving of the diploid set was demonstrated by the average of 23 somatic chromosomes retained in the zygote.
High-resolution sequencing and thorough chromosome tracing showed that homologous chromosomes segregated at random without crossover recombination. In contrast to traditional meiotic division, which typically involves exact homologous pairing and recombination, this process involves random segregation. However, fertilized SCNT oocytes underwent typical cell divisions to create embryos that combined chromosomes from sperm and somatic sources.
Some embryos demonstrated mosaicism, with distinct blastomeres carrying different combinations of somatic and sperm chromosomes. In contrast, other embryos maintained uniform chromosomal content across all blastomeres, as analyzed in early-stage embryos. In addition, replicated chromosomes were faithfully maintained in homogeneous embryos, and mitomeiosis did not interfere with subsequent mitotic cycles.
Although the study demonstrates that experimental ploidy reduction and integration of sperm and somatic genomes are feasible, scientists caution that this remains only a proof-of-concept. Significant research is required before clinical applications, including safety, genomic stability, and long-term developmental potential, can be confirmed. The technique does not yet guarantee fully normal chromosomal segregation or complete recombination.
For patients who are infertile because their oocytes are not functioning, the results offer a possible way forward. The study represents an important step towards human in vitro gametogenesis by demonstrating that human somatic cells can be partially reprogrammed to produce embryos alongside sperm chromosomes. Future research may focus on enhancing chromosome segregation, reducing mosaicism, and ensuring the long-term viability of embryos produced using this method.
The promise of SCNT and mitomeiosis expands fertility options and broadens our understanding of human reproductive biology, as highlighted by this groundbreaking study.
References: Gutierrez MN, Mikhalchenko A, Shishimorova M, et al. Induction of experimental cell division to generate cells with reduced chromosome ploidy. Nat Commun. 2025;16:8340. doi:10.1038/s41467-025-63454-7
