Somatic cell haploidization: an update

Abstract

Oocyte donation is the only method of treating female sterility caused by complete absence of oocytes, with the loss of genetic motherhood. Genetic fatherhood of males with complete absence of spermatozoa can only be restored by assisted reproduction treatment if sperm precursor cells belonging to the male germline can still be recovered from the testis. Otherwise, sperm donation is the only available solution. Somatic nucleus haploidization after injection into previously enucleated donor oocytes (diploid-to-haploid reduction) might enable the reconstruction of new oocytes carrying the complete nuclear genome of female patients lacking their own oocytes. Such newly formed oocytes could subsequently be fertilized by spermatozoa from the patient's husband. In cases of male infertility with complete absence of the germline, the patient's somatic cell nuclei could be injected into the oocytes without previous enucleation, and somatic nucleus haploidization would occur in the presence of the original female nucleus (triploid-to-diploid reduction), hopefully leading to the formation of a diploid embryo. Both interventions differ substantially from cloning because embryos are formed by syngamy with the male and female genomes originating from the two genetic parents, as in natural fertilization. Ultrastructural remodelling of mouse somatic cell nucleoli can be achieved in enucleated metaphase II mouse oocytes. Haploidization has also been attempted with Sertoli cells and with fibroblasts, both of which are also available in male patients. Experiments are currently under way to assess the regularity of chromatid segregation during somatic nucleus haploidization.