Recently,Researchers at the University of Yamanashi in Japan have completed the world's first experiment cloning a female from a male. Using CRISPR gene-editing technology, scientists successfully transformed male mouse embryos into females for the first time, breeding fertile female cloned mice.
This achievement was published in a Nature subsidiary journal and is regarded by the academic community as a milestone breakthrough in mammalian reproductive biology. Monica Ward, a reproductive biologist at the University of Hawaii, commented: "No one has ever done this before."
The core of this technology lies in the precise removal of the Y chromosome. The research team extracted nuclei from male mouse somatic cells and used the CRISPR system to target and cut key sequences on the Y chromosome, causing it to be naturally lost during cell division.
Subsequently, these cells containing only the X chromosome were implanted into enucleated oocytes, and embryos were constructed using somatic cell nuclear transfer technology.
Due to the cellular sex determination mechanism, the absence of the Y chromosome triggers embryonic differentiation towards the female direction, ultimately developing into female individuals with an XX karyotype.
This process is not simply about "removing" the sex-determining gene. Researchers stated that, in addition to the SRY gene, the Y chromosome contains multiple regulatory elements affecting spermatogenesis and metabolism.
Simply knocking out SRY can induce sex reversal but cannot guarantee the normal development of the reproductive system. Therefore, the team adopted a whole-chromosome elimination strategy to ensure that the embryo obtains a complete female genetic background early in development.
Genetic sequencing confirmed that no residual Y chromosome sequences were detected in any of the cloned mice. Furthermore, their ovarian structure, hormone levels, and ability to produce offspring through natural mating were indistinguishable from those of normal female mice.
Scientists pointed out that there is a common preconception that most species require both females and males to reproduce. However, this study suggests that this traditional view may need to be revised.