Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/140530
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Type: | Journal article |
Title: | Dynamics of Mitochondrial DNA Copy Number and Membrane Potential in Mouse Pre-Implantation Embryos: Responses to Diverse Types of Oxidative Stress |
Author: | Winstanley, Y.E. Liu, J. Adhikari, D. Gonzalez, M.B. Russell, D.L. Carroll, J. Robker, R.L. |
Citation: | Genes, 2024; 15(3):15030367-1-15030367-18 |
Publisher: | MDPI AG |
Issue Date: | 2024 |
ISSN: | 2073-4425 2073-4425 |
Statement of Responsibility: | Yasmyn E. Winstanley, Jun Liu, Deepak Adhikari, Macarena B. Gonzalez, Darryl L. Russell, John Carroll, and Rebecca L. Robker |
Abstract: | Mitochondria undergo a myriad of changes during pre-implantation embryo development, including shifts in activity levels and mitochondrial DNA (mtDNA) replication. However, how these distinct aspects of mitochondrial function are linked and their responsiveness to diverse stressors is not well understood. Here, we show that mtDNA content increased between 8-cell embryos and the blastocyst stage, with similar copy numbers per cell in the inner cell mass (ICM) and trophectoderm (TE). In contrast, mitochondrial membrane potential (MMP) was higher in TE than ICM. Culture in ambient oxygen (20% O2 ) altered both aspects of mitochondrial function: the mtDNA copy number was upregulated in ICM, while MMP was diminished in TE. Embryos cultured in 20% O2 also exhibited delayed development kinetics, impaired implantation, and reduced mtDNA levels in E18 fetal liver. A model of oocyte mitochondrial stress using rotenone showed only a modest effect on on-time development and did not alter the mtDNA copy number in ICM; however, following embryo transfer, mtDNA was higher in the fetal heart. Lastly, endogenous mitochondrial dysfunction, induced by maternal age and obesity, altered the blastocyst mtDNA copy number, but not within the ICM. These results demonstrate that mitochondrial activity and mtDNA content exhibit cell-specific changes and are differentially responsive to diverse types of oxidative stress during pre-implantation embryogenesis. |
Keywords: | mtDNA copy number; mitochondrial membrane potential; mitochondrial dysfunction; inner cell mass |
Rights: | © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). |
DOI: | 10.3390/genes15030367 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1130364 http://purl.org/au-research/grants/nhmrc/1117976 |
Published version: | http://dx.doi.org/10.3390/genes15030367 |
Appears in Collections: | Research Outputs |
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hdl_140530.pdf | Published version | 3.43 MB | Adobe PDF | View/Open |
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