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Impact of estrogen deficiency on diaphragm and leg muscle contractile function in female mdx mice
Female carriers of Duchenne muscular dystrophy (DMD) presenting with DMD symptomology similar to males with DMD, such as skeletal muscle weakness and cardiomyopathy, are termed manifesting carriers. There is phenotypic variability among manifesting carriers including the age of onset, which can rang...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011782/ https://www.ncbi.nlm.nih.gov/pubmed/33788896 http://dx.doi.org/10.1371/journal.pone.0249472 |
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author | Vang, Pangdra Baumann, Cory W. Barok, Rebecca Larson, Alexie A. Dougherty, Brendan J. Lowe, Dawn A. |
author_facet | Vang, Pangdra Baumann, Cory W. Barok, Rebecca Larson, Alexie A. Dougherty, Brendan J. Lowe, Dawn A. |
author_sort | Vang, Pangdra |
collection | PubMed |
description | Female carriers of Duchenne muscular dystrophy (DMD) presenting with DMD symptomology similar to males with DMD, such as skeletal muscle weakness and cardiomyopathy, are termed manifesting carriers. There is phenotypic variability among manifesting carriers including the age of onset, which can range from the first to fourth decade of life. In females, estrogen levels typically begin to decline during the fourth decade of life and estrogen deficiency contributes to loss of muscle strength and recovery of strength following injury. Thus, we questioned whether the decline of estrogen impacts the development of DMD symptoms in females. To address this question, we studied 6–8 month-old homozygous mdx female mice randomly assigned to a sham or ovariectomy (OVX) surgical group. In vivo whole-body plethysmography assessed ventilatory function and diaphragm muscle strength was measured in vitro before and after fatigue. Anterior crural muscles were analyzed in vivo for contractile function, fatigue, and in response to eccentric contraction (ECC)-induced injury. For the latter, 50 maximal ECCs were performed by the anterior crural muscles to induce injury. Body mass, uterine mass, hypoxia-hypercapnia ventilatory response, and fatigue index were analyzed by a pooled unpaired t-test. A two-way ANOVA was used to analyze ventilatory measurements. Fatigue and ECC-injury recovery experiments were analyzed by a two-way repeated-measures ANOVA. Results show no differences between sham and OVX mdx mice in ventilatory function, strength, or recovery of strength after fatigue in the diaphragm muscle or anterior crural muscles (p ≥ 0.078). However, OVX mice had significantly greater eccentric torque loss and blunted recovery of strength after ECC-induced injury compared to sham mice (p ≤ 0.019). Although the results show that loss of estrogen has minimal impact on skeletal muscle contractile function in female mdx mice, a key finding suggests that estrogen is important in muscle recovery in female mdx mice after injury. |
format | Online Article Text |
id | pubmed-8011782 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-80117822021-04-07 Impact of estrogen deficiency on diaphragm and leg muscle contractile function in female mdx mice Vang, Pangdra Baumann, Cory W. Barok, Rebecca Larson, Alexie A. Dougherty, Brendan J. Lowe, Dawn A. PLoS One Research Article Female carriers of Duchenne muscular dystrophy (DMD) presenting with DMD symptomology similar to males with DMD, such as skeletal muscle weakness and cardiomyopathy, are termed manifesting carriers. There is phenotypic variability among manifesting carriers including the age of onset, which can range from the first to fourth decade of life. In females, estrogen levels typically begin to decline during the fourth decade of life and estrogen deficiency contributes to loss of muscle strength and recovery of strength following injury. Thus, we questioned whether the decline of estrogen impacts the development of DMD symptoms in females. To address this question, we studied 6–8 month-old homozygous mdx female mice randomly assigned to a sham or ovariectomy (OVX) surgical group. In vivo whole-body plethysmography assessed ventilatory function and diaphragm muscle strength was measured in vitro before and after fatigue. Anterior crural muscles were analyzed in vivo for contractile function, fatigue, and in response to eccentric contraction (ECC)-induced injury. For the latter, 50 maximal ECCs were performed by the anterior crural muscles to induce injury. Body mass, uterine mass, hypoxia-hypercapnia ventilatory response, and fatigue index were analyzed by a pooled unpaired t-test. A two-way ANOVA was used to analyze ventilatory measurements. Fatigue and ECC-injury recovery experiments were analyzed by a two-way repeated-measures ANOVA. Results show no differences between sham and OVX mdx mice in ventilatory function, strength, or recovery of strength after fatigue in the diaphragm muscle or anterior crural muscles (p ≥ 0.078). However, OVX mice had significantly greater eccentric torque loss and blunted recovery of strength after ECC-induced injury compared to sham mice (p ≤ 0.019). Although the results show that loss of estrogen has minimal impact on skeletal muscle contractile function in female mdx mice, a key finding suggests that estrogen is important in muscle recovery in female mdx mice after injury. Public Library of Science 2021-03-31 /pmc/articles/PMC8011782/ /pubmed/33788896 http://dx.doi.org/10.1371/journal.pone.0249472 Text en © 2021 Vang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Article Vang, Pangdra Baumann, Cory W. Barok, Rebecca Larson, Alexie A. Dougherty, Brendan J. Lowe, Dawn A. Impact of estrogen deficiency on diaphragm and leg muscle contractile function in female mdx mice |
title | Impact of estrogen deficiency on diaphragm and leg muscle contractile function in female mdx mice |
title_full | Impact of estrogen deficiency on diaphragm and leg muscle contractile function in female mdx mice |
title_fullStr | Impact of estrogen deficiency on diaphragm and leg muscle contractile function in female mdx mice |
title_full_unstemmed | Impact of estrogen deficiency on diaphragm and leg muscle contractile function in female mdx mice |
title_short | Impact of estrogen deficiency on diaphragm and leg muscle contractile function in female mdx mice |
title_sort | impact of estrogen deficiency on diaphragm and leg muscle contractile function in female mdx mice |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8011782/ https://www.ncbi.nlm.nih.gov/pubmed/33788896 http://dx.doi.org/10.1371/journal.pone.0249472 |
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