Role of the mitochondrial genome in assisted reproductive technologies and embryonic stem cell-based therapeutic cloning
Carol A. Brenner A D E , H. Michael Kubisch B and Kenneth E. Pierce C
+ Author Affiliations
- Author Affiliations
A University of New Orleans, New Orleans, LA 70148, USA.
B Tulane National Primate Research Center, Covington, LA 70433, USA.
C Department of Biology, Brandeis University, Waltham, MA 02454, USA.
D Tulane Institute for Reproductive Medicine, Center for Excellence in Women’s Health, New Orleans, LA 70112, USA.
E To whom correspondence should be addressed. email: cbrenner@uno.edu
Reproduction, Fertility and Development 16(7) 743-751 https://doi.org/10.1071/RD04107
Submitted: 29 September 2004 Accepted: 19 October 2004 Published: 9 December 2004
Abstract
Mitochondria play a pivotal role in cellular metabolism and are important determinants of embryonic development. Mitochondrial function and biogenesis rely on an intricate coordination of regulation and expression of nuclear and mitochondrial genes. For example, several nucleus-derived transcription factors, such as mitochondrial transcription factor A, are required for mitochondrial DNA replication. Mitochondrial inheritance is strictly maternal while paternally-derived mitochondria are selectively eliminated during early embryonic cell divisions. However, there are reports from animals as well as human patients that paternal mitochondria can occasionally escape elimination, which in some cases has led to severe pathologies. The resulting existence of different mitochondrial genomes within the same cell has been termed mitochondrial heteroplasmy. The increasing use of invasive techniques in assisted reproduction in humans has raised concerns that one of the outcomes of such techniques is an increase in the incidence of mitochondrial heteroplasmy. Indeed, there is evidence that heteroplasmy is a direct consequence of ooplasm transfer, a technique that was used to ‘rescue’ oocytes from older women by injecting ooplasm from young oocytes. Mitochondria from donor and recipient were found in varying proportions in resulting children. Heteroplasmy is also a byproduct of nuclear transfer, as has been shown in studies on cloned sheep, cattle and monkeys. As therapeutic cloning will depend on nuclear transfer into oocytes and the subsequent generation of embryonic stem cells from resulting blastocysts, the prospect of mitochondrial heteroplasmy and its potential problems necessitate further studies in this area.
Extra keywords: assisted reproductive technologies, cytoplasmic transfer, embryonic stem cells, mitochondrial heteroplasmy, mitochondrial transcription factors.
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