Current status of interspecies somatic cell nuclear transfer and meta-analysis of the effects of phylogenetic distance on embryonic and fetal development

Interspecies somatic cell nuclear transfer (iSCNT) has the capacity to rescue endangered species, ethically produce human embryonic stem cells, and allow for more specific analysis of pre-implantation embryos. However, several obstacles negatively affect iSCNT efficiency. Over 100 iSCNT studies have been published between 1999 and the spring of 2023. This review details the possible benefits of iSCNT, describes the hypothesized issues that prevented the development of some embryos and/or live offspring from developing; and analyzes the cleavage, blastocyst, pregnancy, live birth, and iSCNT efficiency rates based on published data. Embryos produced by iSCNT may help with the rescue of endangered species and the production of human embryonic stem cells with the use of oocytes from domestic species, as well as in-depth analyses of embryonic genome activation (EGA) and mRNA transcripts. But the combination of the cells of two species in a single embryo presents several challenges: lack of EGA synchronisation, presence of mitochondrial DNA (mtDNA) from both species in the embryo, requirement of cell and embryo culture optimization for each species combination, lack of embryo transfer data, and an extremely low overall efficiency in terms of producing live offspring. Additional research on the aforementioned topics is warranted to increase iSCNT efficiency. This review of interspecies somatic cell nuclear transfer (iSCNT) provides a summary and meta-analysis of 143 studies published between 1999 (when the earliest iSCNT manuscript was published) and spring of 2023. In vitro and in vivo developmental rates were compared based on oocyte species and phylogenetic distance between oocyte species and donor cell species. The production of iSCNT embryos has great potential in several areas of research - rescue of endangered species, ethical production of human embryonic stem cells, and specification of donor cell and recipient oocyte influences on iSCNT embryo development. Obstacles to development include mitochondrial heteroplasmy, phylogenetic distance between the two species, timing of embryonic genome activation, culture of donor cells and reconstructed embryos, and optimization of embryo transfer. Though live offspring have been produced in twelve studies, the overall efficiency rate based on the successful iSCNT studies is only 0.29%. We conclude that additional research is warranted to improve development rate, allowing future scientists to use iSCNT for their research goals.image