Human artificial oocytes from patients’ somatic cells: past, present and future

Abstract

The first attempts at generating functional human oocytes by using transfer of patients’ somatic cell nuclei, as DNA source, into donor enucleated oocytes date back to the early 2000s. After initial attempts, that gave rather encouraging results, the technique was abandoned because of adverse results with this technique in the mouse model. Priority was then given to the use of induced pluripotent stem (iPS) cells, based on excellent results in the mouse, where mature oocytes and live healthy offspring were achieved. However, these results could not be reproduced in humans, and oogenesis with human iPS cells did not continue beyond the stage of oogonium. These data suggest that the use of enucleated donor oocytes will be necessary to achieve fertilizable human oocytes with somatic cell-derived DNA. The main problem of all these techniques is that they have to meet with two, sometimes contradictory, requirements: the haploidisation of somatic cell-derived DNA, on the one hand, and the remodelling/reprogramming of DNA of somatic cell origin, so as to be capable of supporting all stages of preimplantation and postimplantation development and to give rise to all cell types of the future organism. Further research is needed to determine the optimal strategy to cope with these two requirements.

Haploidy in somatic cells is induced by mature oocytes in mice

“…However, there are debates for the success of chromosome segregation of somatic nucleus 2 , 20 . The first attempt of somatic haploidization was performed using the mature oocytes (MII) in human 7 .…”

“…Several studies attempted to induce somatic haploidy. However, the diploid somatic cells that transferred into enucleated oocytes to achieve the haploid nucleus resulted in limited development of the preimplantation embryos 2 . In mice, the somatic cells such as cumulus or fibroblasts were transferred to immature germinal vesicle (GV) or mature MII oocytes to induce haploid chromosomes, but the reconstructed chromosomes exhibited abnormalities in the separation and alignment processes and embryo development was not observed 3 – 6 .…”

Artificial Oocyte: Development and Potential Application

“…The differentiation of human PSCs has only been achieved up to the oogonium. Thus, the formation of artificial oocytes in humans must be performed either by haploidization of the adult somatic cells, or by transferring the oogonium nucleus obtained from PSCs to the oocytes; of course, the latter is preferable because it is cheaper, faster, and easier for the patient [ 151 ]. For example, as research by Tian et al (2019) showed, mouse granulosa cells can be converted to PSCs by chemical induction, and these cells differentiate more favorably into functional oocytes [ 87 ].…”

Haploidy of somatic cells in mouse oocyte using somatic cell nuclear transfer

“…Until now, several investigators have attempted somatic haploidization. To induce haploidization of the diploid somatic genome, somatic cells were transferred into enucleated oocytes (Tesarik et al, 2021). However, earlier studies have shown abnormal separation and alignment processes in reconstructed chromosomes and limited development of the preimplantation embryos (Fulka et al, 2002;Palermo et al, 2002;Tateno et al, 2003A;Chang et al, 2004;Tesarik et al, 2021).…”

“…To induce haploidization of the diploid somatic genome, somatic cells were transferred into enucleated oocytes (Tesarik et al, 2021). However, earlier studies have shown abnormal separation and alignment processes in reconstructed chromosomes and limited development of the preimplantation embryos (Fulka et al, 2002;Palermo et al, 2002;Tateno et al, 2003A;Chang et al, 2004;Tesarik et al, 2021). One research group Kang E, Associate professor, https://orcid.org/0000-0002-7240-7868 ABSTRACT Haploidization in somatic cells is the process of reducing the diploid somatic chromosomes to haploid.…”