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Impact of exercise on oocyte quality in the POLG mitochondrial DNA mutator mouse

The mtDNA ‘mutator’ mouse, also called the ‘POLG’ mouse, is a well-characterized model frequently used for studies of progeroid aging. Harboring a mutation in the proofreading domain of the mitochondrial polymerase, polymerase-γ (Polg), POLG mice acquire mtDNA mutations at an accelerated rate. This...

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Autores principales: Faraci, Christine, Annis, Sofia, Jin, Joyce, Li, Housaiyin, Khrapko, Konstantin, Woods, Dori C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6074767/
https://www.ncbi.nlm.nih.gov/pubmed/29875308
http://dx.doi.org/10.1530/REP-18-0061
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author Faraci, Christine
Annis, Sofia
Jin, Joyce
Li, Housaiyin
Khrapko, Konstantin
Woods, Dori C
author_facet Faraci, Christine
Annis, Sofia
Jin, Joyce
Li, Housaiyin
Khrapko, Konstantin
Woods, Dori C
author_sort Faraci, Christine
collection PubMed
description The mtDNA ‘mutator’ mouse, also called the ‘POLG’ mouse, is a well-characterized model frequently used for studies of progeroid aging. Harboring a mutation in the proofreading domain of the mitochondrial polymerase, polymerase-γ (Polg), POLG mice acquire mtDNA mutations at an accelerated rate. This results in premature mitochondrial dysfunction and a systemic aging phenotype. Previous work has demonstrated that the progeroid phenotype in POLG is attenuated following endurance exercise, the only reported intervention to extend health span and lifespan of these mice. Herein, oocyte quality was evaluated in sedentary and exercised POLG mice. In mice homozygous for the Polg mutation, litter size is dramatically reduced as compared to heterozygous Polg mice. Following ovarian hyper-stimulation, oocytes were retrieved until 9 months of age in exercised and sedentary groups, with no oocytes ovulated thereafter. Although ovulated oocyte numbers were not impacted by exercise, we did find a modest improvement in both the ovarian follicle reserve and in oocyte quality based on meiotic spindle assembly, chromosomal segregation and mitochondrial distribution at 7 months of age in exercised POLG mice as compared to sedentary counterparts. Of note, analysis of mtDNA mutational load revealed no differences between exercised and sedentary groups. Collectively, these data indicate that exercise differentially influences somatic tissues of the POLG mouse as compared to oocytes, highlighting important mechanistic differences between mitochondrial regulatory mechanisms in the soma and the germline.
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spelling pubmed-60747672018-08-06 Impact of exercise on oocyte quality in the POLG mitochondrial DNA mutator mouse Faraci, Christine Annis, Sofia Jin, Joyce Li, Housaiyin Khrapko, Konstantin Woods, Dori C Reproduction Research The mtDNA ‘mutator’ mouse, also called the ‘POLG’ mouse, is a well-characterized model frequently used for studies of progeroid aging. Harboring a mutation in the proofreading domain of the mitochondrial polymerase, polymerase-γ (Polg), POLG mice acquire mtDNA mutations at an accelerated rate. This results in premature mitochondrial dysfunction and a systemic aging phenotype. Previous work has demonstrated that the progeroid phenotype in POLG is attenuated following endurance exercise, the only reported intervention to extend health span and lifespan of these mice. Herein, oocyte quality was evaluated in sedentary and exercised POLG mice. In mice homozygous for the Polg mutation, litter size is dramatically reduced as compared to heterozygous Polg mice. Following ovarian hyper-stimulation, oocytes were retrieved until 9 months of age in exercised and sedentary groups, with no oocytes ovulated thereafter. Although ovulated oocyte numbers were not impacted by exercise, we did find a modest improvement in both the ovarian follicle reserve and in oocyte quality based on meiotic spindle assembly, chromosomal segregation and mitochondrial distribution at 7 months of age in exercised POLG mice as compared to sedentary counterparts. Of note, analysis of mtDNA mutational load revealed no differences between exercised and sedentary groups. Collectively, these data indicate that exercise differentially influences somatic tissues of the POLG mouse as compared to oocytes, highlighting important mechanistic differences between mitochondrial regulatory mechanisms in the soma and the germline. Bioscientifica Ltd 2018-06-05 /pmc/articles/PMC6074767/ /pubmed/29875308 http://dx.doi.org/10.1530/REP-18-0061 Text en © 2018 The authors http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research
Faraci, Christine
Annis, Sofia
Jin, Joyce
Li, Housaiyin
Khrapko, Konstantin
Woods, Dori C
Impact of exercise on oocyte quality in the POLG mitochondrial DNA mutator mouse
title Impact of exercise on oocyte quality in the POLG mitochondrial DNA mutator mouse
title_full Impact of exercise on oocyte quality in the POLG mitochondrial DNA mutator mouse
title_fullStr Impact of exercise on oocyte quality in the POLG mitochondrial DNA mutator mouse
title_full_unstemmed Impact of exercise on oocyte quality in the POLG mitochondrial DNA mutator mouse
title_short Impact of exercise on oocyte quality in the POLG mitochondrial DNA mutator mouse
title_sort impact of exercise on oocyte quality in the polg mitochondrial dna mutator mouse
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6074767/
https://www.ncbi.nlm.nih.gov/pubmed/29875308
http://dx.doi.org/10.1530/REP-18-0061
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