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Paternal Exercise Improves the Metabolic Health of Offspring via Epigenetic Modulation of the Germline

Background/Aims: Epigenetic regulation is considered the main molecular mechanism underlying the developmental origin of health and disease’s (DOHAD) hypothesis. Previous studies that have investigated the role of paternal exercise on the metabolic health of the offspring did not control for the amo...

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Autores principales: Costa-Júnior, José Maria, Ferreira, Sandra Mara, Kurauti, Mirian Ayumi, Bernstein, Diana L., Ruano, Elena G., Kameswaran, Vasumathi, Schug, Jonathan, Freitas-Dias, Ricardo, Zoppi, Claudio C., Boschero, Antonio C., de Oliveira, Camila A. M., Santos, Gustavo J., Carneiro, Everardo M., Kaestner, Klaus H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8744992/
https://www.ncbi.nlm.nih.gov/pubmed/35008427
http://dx.doi.org/10.3390/ijms23010001
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author Costa-Júnior, José Maria
Ferreira, Sandra Mara
Kurauti, Mirian Ayumi
Bernstein, Diana L.
Ruano, Elena G.
Kameswaran, Vasumathi
Schug, Jonathan
Freitas-Dias, Ricardo
Zoppi, Claudio C.
Boschero, Antonio C.
de Oliveira, Camila A. M.
Santos, Gustavo J.
Carneiro, Everardo M.
Kaestner, Klaus H.
author_facet Costa-Júnior, José Maria
Ferreira, Sandra Mara
Kurauti, Mirian Ayumi
Bernstein, Diana L.
Ruano, Elena G.
Kameswaran, Vasumathi
Schug, Jonathan
Freitas-Dias, Ricardo
Zoppi, Claudio C.
Boschero, Antonio C.
de Oliveira, Camila A. M.
Santos, Gustavo J.
Carneiro, Everardo M.
Kaestner, Klaus H.
author_sort Costa-Júnior, José Maria
collection PubMed
description Background/Aims: Epigenetic regulation is considered the main molecular mechanism underlying the developmental origin of health and disease’s (DOHAD) hypothesis. Previous studies that have investigated the role of paternal exercise on the metabolic health of the offspring did not control for the amount and intensity of the training or possible effects of adaptation to exercise and produced conflicting results regarding the benefits of parental exercise to the next generation. We employed a precisely regulated exercise regimen to study the transgenerational inheritance of improved metabolic health. Methods: We subjected male mice to a well-controlled exercise -training program to investigate the effects of paternal exercise on glucose tolerance and insulin sensitivity in their adult progeny. To investigate the molecular mechanisms of epigenetic inheritance, we determined chromatin markers in the skeletal muscle of the offspring and the paternal sperm. Results: Offspring of trained male mice exhibited improved glucose homeostasis and insulin sensitivity. Paternal exercise modulated the DNA methylation profile of PI3Kca and the imprinted H19/Igf2 locus at specific differentially methylated regions (DMRs) in the skeletal muscle of the offspring, which affected their gene expression. Remarkably, a similar DNA methylation profile at the PI3Kca, H19, and Igf2 genes was present in the progenitor sperm indicating that exercise-induced epigenetic changes that occurred during germ cell development contributed to transgenerational transmission. Conclusion: Paternal exercise might be considered as a strategy that could promote metabolic health in the offspring as the benefits can be inherited transgenerationally.
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spelling pubmed-87449922022-01-11 Paternal Exercise Improves the Metabolic Health of Offspring via Epigenetic Modulation of the Germline Costa-Júnior, José Maria Ferreira, Sandra Mara Kurauti, Mirian Ayumi Bernstein, Diana L. Ruano, Elena G. Kameswaran, Vasumathi Schug, Jonathan Freitas-Dias, Ricardo Zoppi, Claudio C. Boschero, Antonio C. de Oliveira, Camila A. M. Santos, Gustavo J. Carneiro, Everardo M. Kaestner, Klaus H. Int J Mol Sci Article Background/Aims: Epigenetic regulation is considered the main molecular mechanism underlying the developmental origin of health and disease’s (DOHAD) hypothesis. Previous studies that have investigated the role of paternal exercise on the metabolic health of the offspring did not control for the amount and intensity of the training or possible effects of adaptation to exercise and produced conflicting results regarding the benefits of parental exercise to the next generation. We employed a precisely regulated exercise regimen to study the transgenerational inheritance of improved metabolic health. Methods: We subjected male mice to a well-controlled exercise -training program to investigate the effects of paternal exercise on glucose tolerance and insulin sensitivity in their adult progeny. To investigate the molecular mechanisms of epigenetic inheritance, we determined chromatin markers in the skeletal muscle of the offspring and the paternal sperm. Results: Offspring of trained male mice exhibited improved glucose homeostasis and insulin sensitivity. Paternal exercise modulated the DNA methylation profile of PI3Kca and the imprinted H19/Igf2 locus at specific differentially methylated regions (DMRs) in the skeletal muscle of the offspring, which affected their gene expression. Remarkably, a similar DNA methylation profile at the PI3Kca, H19, and Igf2 genes was present in the progenitor sperm indicating that exercise-induced epigenetic changes that occurred during germ cell development contributed to transgenerational transmission. Conclusion: Paternal exercise might be considered as a strategy that could promote metabolic health in the offspring as the benefits can be inherited transgenerationally. MDPI 2021-12-21 /pmc/articles/PMC8744992/ /pubmed/35008427 http://dx.doi.org/10.3390/ijms23010001 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/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/).
spellingShingle Article
Costa-Júnior, José Maria
Ferreira, Sandra Mara
Kurauti, Mirian Ayumi
Bernstein, Diana L.
Ruano, Elena G.
Kameswaran, Vasumathi
Schug, Jonathan
Freitas-Dias, Ricardo
Zoppi, Claudio C.
Boschero, Antonio C.
de Oliveira, Camila A. M.
Santos, Gustavo J.
Carneiro, Everardo M.
Kaestner, Klaus H.
Paternal Exercise Improves the Metabolic Health of Offspring via Epigenetic Modulation of the Germline
title Paternal Exercise Improves the Metabolic Health of Offspring via Epigenetic Modulation of the Germline
title_full Paternal Exercise Improves the Metabolic Health of Offspring via Epigenetic Modulation of the Germline
title_fullStr Paternal Exercise Improves the Metabolic Health of Offspring via Epigenetic Modulation of the Germline
title_full_unstemmed Paternal Exercise Improves the Metabolic Health of Offspring via Epigenetic Modulation of the Germline
title_short Paternal Exercise Improves the Metabolic Health of Offspring via Epigenetic Modulation of the Germline
title_sort paternal exercise improves the metabolic health of offspring via epigenetic modulation of the germline
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8744992/
https://www.ncbi.nlm.nih.gov/pubmed/35008427
http://dx.doi.org/10.3390/ijms23010001
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