Somatic cell nuclear transfer (SCNT) enables the direct reprogramming of somatic cells into functional oocytes, albeit with a diploid genome. To address ploidy reduction, we investigated an experimental reductive cell division process, termed mitomeiosis, wherein non-replicated somatic genomes are prematurely forced to divide following transplantation into the metaphase cytoplasm of enucleated human oocytes.
However, despite fertilization with sperm, SCNT oocytes remained arrested at the metaphase stage, indicating activation failure. Artificial activation using a selective cyclin-dependent kinase inhibitor successfully bypassed this arrest, inducing the segregation of somatic chromosomes into a zygotic pronucleus and a polar body.
Comprehensive chromosome tracing via sequencing revealed that homologous chromosome segregation occurred randomly and without crossover recombination. Nonetheless, an average of 23 somatic chromosomes were retained within the zygote, demonstrating the feasibility of experimentally halving the diploid chromosome set.
Fertilized human SCNT oocytes progressed through normal embryonic cell divisions, ultimately developing into embryos with integrated somatic and sperm-derived chromosomes. While our study demonstrates the potential of mitomeiosis for in vitro gametogenesis, at this stage it remains just a proof of concept and further research is required to ensure efficacy and safety before future clinical applications.
Somatic cell nuclear transfer (SCNT) has enabled the direct reprogramming of somatic cells into functional oocytes. However, despite advances in SCNT technology, achieving diploid oocytes with normal ploidy remains a significant challenge.
To address this issue, we have investigated an experimental reductive cell division process called mitomeiosis, which involves non-replicated somatic genomes being prematurely forced to divide following transplantation into the metaphase cytoplasm of enucleated human oocytes.
Our results show that artificial activation using a selective cyclin-dependent kinase inhibitor successfully bypassed the activation failure and induced the segregation of somatic chromosomes into a zygotic pronucleus and a polar body.
Comprehensive chromosome tracing via sequencing revealed that homologous chromosome segregation occurred randomly and without crossover recombination, but an average of 23 somatic chromosomes were retained within the zygote.
Fertilized human SCNT oocytes progressed through normal embryonic cell divisions and developed into embryos with integrated somatic and sperm-derived chromosomes.
However, while our study demonstrates the potential of mitomeiosis for in vitro gametogenesis, further research is required to ensure efficacy and safety before future clinical applications.
The development of this technology has significant implications for the treatment of infertility and the creation of genetically related children using donor gametes.
However, further studies are needed to optimize the process and minimize potential complications.
Source: https://www.nature.com/articles/s41467-025-63454-7