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Updated: Apr 2, 2026
Use of Bisection to Reduce Mitochondrial DNA in the Bovine Oocyte
Published on: July 6, 2022
Preimplantation death of xenomitochondrial mouse embryo harbouring bovine mitochondria
Manabu Kawahara1, Shiori Koyama1, Satomi Iimura1
1Laboratory of Animal Breeding and Reproduction, Research Faculty of Agriculture, Hokkaido University, Kita-ku Kita 9 Nishi 9, Sapporo 060-8589, Japan.
Abstract:
Mitochondria, cellular organelles playing essential roles in eukaryotic cell metabolism, are thought to have evolved from bacteria. The organization of mtDNA is remarkably uniform across species, reflecting its vital and conserved role in oxidative phosphorylation (OXPHOS). Our objectives were to evaluate the compatibility of xenogeneic mitochondria in the development of preimplantation embryos in mammals. Mouse embryos harbouring bovine mitochondria (mtB-M embryos) were prepared by the cell-fusion technique employing the haemagglutinating virus of Japan (HVJ). The mtB-M embryos showed developmental delay at embryonic days (E) 3.5 after insemination. Furthermore, none of the mtB-M embryos could implant into the maternal uterus after embryo transfer, whereas control mouse embryos into which mitochondria from another mouse had been transferred developed as well as did non-manipulated embryos. When we performed quantitative PCR (qPCR) of mouse and bovine ND5, we found that the mtB-M embryos contained 8.3% of bovine mitochondria at the blastocyst stage. Thus, contamination with mitochondria from another species induces embryonic lethality prior to implantation into the maternal uterus. The heteroplasmic state of these xenogeneic mitochondria could have detrimental effects on preimplantation development, leading to preservation of species-specific mitochondrial integrity in mammals.
Insights
Introducing foreign mitochondria into mouse embryos halted their development before implantation. This suggests species-specific mitochondrial integrity is crucial for early mammalian embryonic development.
Area of Science:
- Cell Biology
- Developmental Biology
- Genetics
Background:
- Mitochondria, essential for eukaryotic cell metabolism, are believed to originate from bacteria.
- Mitochondrial DNA (mtDNA) organization is highly conserved across species, vital for oxidative phosphorylation (OXPHOS).
Purpose of the Study:
- To investigate the compatibility of xenogeneic (foreign) mitochondria in mammalian preimplantation embryo development.
- To determine the impact of interspecies mitochondrial transfer on embryonic viability.
Main Methods:
- Mouse embryos were fused with bovine cells using the haemagglutinating virus of Japan (HVJ) to create xenogeneic mitochondrial embryos (mtB-M embryos).
- Embryo development was monitored, and implantation rates were assessed after transfer into surrogate mothers.
- Quantitative PCR (qPCR) was used to measure the proportion of bovine mitochondrial DNA (mtDNA) in mouse embryos.
Main Results:
- mtB-M embryos exhibited developmental delays at embryonic day 3.5.
- No mtB-M embryos successfully implanted into the maternal uterus.
- Control embryos with intraspecies mitochondria or no manipulation developed normally.
- Bovine mtDNA constituted 8.3% of total mtDNA in blastocyst-stage mtB-M embryos.
Conclusions:
- Contamination with xenogeneic mitochondria leads to embryonic lethality before implantation in mammals.
- The heteroplasmic state of foreign mitochondria may disrupt preimplantation development.
- This finding underscores the importance of species-specific mitochondrial integrity for successful mammalian reproduction.
