Donor-host mitochondrial compatibility improves efficiency of bovine somatic cell nuclear transfer

Abstract

BackgroundThe interaction between the karyoplast and cytoplast plays an important role in the efficiency of somatic cell nuclear transfer (SCNT), but the underlying mechanism remains unclear. It is generally accepted that in nuclear transfer embryos, the reprogramming of gene expression is induced by epigenetic mechanisms and does not involve modifications of DNA sequences. In cattle, oocytes with various mitochondrial DNA (mtDNA) haplotypes usually have different ATP content and can further affect the efficiency of in vitro production of embryos. As mtDNA comes from the recipient oocyte during SCNT and is regulated by genes in the donor nucleus, it is a perfect model to investigate the interaction between donor nuclei and host oocytes in SCNT.ResultsWe investigated whether the in vitro development of reconstructed bovine embryos produced by SCNT would be influenced by mtDNA haplotype compatibility between the oocytes and donor cells. Embryos from homotype A-A or B-B showed significantly higher developmental ability at blastocyst stages than the heterotype A-B or B-A combinations. Post-implantation development ability, pregnancy rate up to day 90 of gestation, as well as percent of term births were higher in the homotype SCNT groups than in the heterotype groups. In addition, homotype and heterotype SCNT embryos showed different methylation patterns of histone 3-lysine 9 (H3K9) genome-wide and at pluripotency-related genes (Oct-4, Sox-2, Nanog).ConclusionBoth histone and DNA methylation show that homotype SCNT blastocysts have a more successful epigenetic asymmetry pattern than heterotype SCNT blastocysts, which indicates more complete nuclear reprogramming. This may result from variability in their epigenetic patterns and responses to nuclear reprogramming. This suggests that the compatibility of mtDNA haplotypes between donor cells and host oocytes can significantly affect the developmental competence of reconstructed embryos in SCNT, and may include an epigenetic mechanism.

Comparative Proteomic Analysis of Liver Mitochondrial Proteins Derived from Cloned Adult Pigs Reconstructed with Meishan Pig Fibroblast Cells and European Pig Enucleated Oocytes

“…Previous reports provided evidence for oocyte mtDNA haplotype influences on SCNT efficiency in cattle [12,13,32]. Yan et al [14,33] demonstrated that donor-host mtDNA haplotype compatibility improved bovine SCNT efficiency; thus, homotypic SCNT blastocysts possess a more successful epigenetic symmetry pattern than heterotypic SCNT blastocysts. It is unclear in the present study whether the differential protein expression patterning was reflective of a donor-host mtDNA incompatibility.…”

“…Where heteroplasmy was observed, the majority of mitochondrial DNA (mtDNA) did originate from the recipient oocyte. Previous reports also demonstrated that the oocyte mtDNA haplotype influenced SCNT efficiency [12][13][14]. Indeed, the interaction between the cytoplasm and nuclear genomes is of critical importance in interspecies SCNT (iSCNT), as most of the mRNAs, proteins, organelles and other cytoplasmic components are contributed by the oocyte.…”

Maternal control of oocyte quality in cattle “a review”

“…An explanation for the highest developmental competence of hybrid oocytes is due to the genetic heterogeneity of the hybrid recipient cytoplasm which provides more opportunities for reprogramming and embryo development. Another possible explanation, based on our further studies, is the nuclear-mitochondrial interactions are normal because in hybrid cloned embryos, both nuclear and mitochondrial components came from same breed (due to the exclusively maternal inheritance of mitochondria) (Yang et al, 2006;Yan et al, 2010).…”

Mitochondrial DNA transmission and confounding mitochondrial influences in cloned cattle and pigs

“…Previous reports provided evidence for the influence of oocyte mtDNA haplotype on SCNT efficiency in cattle [70][71][72]. The mitochondria transmitted by nuclear transfer may affect the phenotypic changes observed in cloned animals [73].…”