Parental Diabetes: The Akita Mouse as a Model of the Effects of Maternal and Paternal Hyperglycemia in Wildtype Offspring

AIM/HYPOTHESIS: Maternal diabetes and high-fat feeding during pregnancy have been linked to later life outcomes in offspring. To investigate the effects of both maternal and paternal hyperglycemia on offspring phenotypes, we utilized an autosomal dominant mouse model of diabetes (hypoinsulinemic hyp...

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Autores principales: Grasemann, Corinna, Devlin, Maureen J., Rzeczkowska, Paulina A., Herrmann, Ralf, Horsthemke, Bernhard, Hauffa, Berthold P., Grynpas, Marc, Alm, Christina, Bouxsein, Mary L., Palmert, Mark R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509145/
https://www.ncbi.nlm.nih.gov/pubmed/23209676
http://dx.doi.org/10.1371/journal.pone.0050210
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author Grasemann, Corinna
Devlin, Maureen J.
Rzeczkowska, Paulina A.
Herrmann, Ralf
Horsthemke, Bernhard
Hauffa, Berthold P.
Grynpas, Marc
Alm, Christina
Bouxsein, Mary L.
Palmert, Mark R.
author_facet Grasemann, Corinna
Devlin, Maureen J.
Rzeczkowska, Paulina A.
Herrmann, Ralf
Horsthemke, Bernhard
Hauffa, Berthold P.
Grynpas, Marc
Alm, Christina
Bouxsein, Mary L.
Palmert, Mark R.
author_sort Grasemann, Corinna
collection PubMed
description AIM/HYPOTHESIS: Maternal diabetes and high-fat feeding during pregnancy have been linked to later life outcomes in offspring. To investigate the effects of both maternal and paternal hyperglycemia on offspring phenotypes, we utilized an autosomal dominant mouse model of diabetes (hypoinsulinemic hyperglycemia in Akita mice). We determined metabolic and skeletal phenotypes in wildtype offspring of Akita mothers and fathers. RESULTS: Both maternal and paternal diabetes resulted in phenotypic changes in wildtype offspring. Phenotypic changes were more pronounced in male offspring than in female offspring. Maternal hyperglycemia resulted in metabolic and skeletal phenotypes in male wildtype offspring. Decreased bodyweight and impaired glucose tolerance were observed as were reduced whole body bone mineral density and reduced trabecular bone mass. Phenotypic changes in offspring of diabetic fathers differed in effect size from changes in offspring of diabetic mothers. Male wildtype offspring developed a milder metabolic phenotype, but a more severe skeletal phenotype. Female wildtype offspring of diabetic fathers were least affected. CONCLUSIONS: Both maternal and paternal diabetes led to the development of metabolic and skeletal changes in wildtype offspring, with a greater effect of maternal diabetes on metabolic parameters and of paternal diabetes on skeletal development. The observed changes are unlikely to derive from Mendelian inheritance, since the investigated offspring did not inherit the Akita mutation. While fetal programming may explain the phenotypic changes in offspring exposed to maternal diabetes in-utero, the mechanism underlying the effect of paternal diabetes on wildtype offspring is unclear.
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spelling pubmed-35091452012-12-03 Parental Diabetes: The Akita Mouse as a Model of the Effects of Maternal and Paternal Hyperglycemia in Wildtype Offspring Grasemann, Corinna Devlin, Maureen J. Rzeczkowska, Paulina A. Herrmann, Ralf Horsthemke, Bernhard Hauffa, Berthold P. Grynpas, Marc Alm, Christina Bouxsein, Mary L. Palmert, Mark R. PLoS One Research Article AIM/HYPOTHESIS: Maternal diabetes and high-fat feeding during pregnancy have been linked to later life outcomes in offspring. To investigate the effects of both maternal and paternal hyperglycemia on offspring phenotypes, we utilized an autosomal dominant mouse model of diabetes (hypoinsulinemic hyperglycemia in Akita mice). We determined metabolic and skeletal phenotypes in wildtype offspring of Akita mothers and fathers. RESULTS: Both maternal and paternal diabetes resulted in phenotypic changes in wildtype offspring. Phenotypic changes were more pronounced in male offspring than in female offspring. Maternal hyperglycemia resulted in metabolic and skeletal phenotypes in male wildtype offspring. Decreased bodyweight and impaired glucose tolerance were observed as were reduced whole body bone mineral density and reduced trabecular bone mass. Phenotypic changes in offspring of diabetic fathers differed in effect size from changes in offspring of diabetic mothers. Male wildtype offspring developed a milder metabolic phenotype, but a more severe skeletal phenotype. Female wildtype offspring of diabetic fathers were least affected. CONCLUSIONS: Both maternal and paternal diabetes led to the development of metabolic and skeletal changes in wildtype offspring, with a greater effect of maternal diabetes on metabolic parameters and of paternal diabetes on skeletal development. The observed changes are unlikely to derive from Mendelian inheritance, since the investigated offspring did not inherit the Akita mutation. While fetal programming may explain the phenotypic changes in offspring exposed to maternal diabetes in-utero, the mechanism underlying the effect of paternal diabetes on wildtype offspring is unclear. Public Library of Science 2012-11-28 /pmc/articles/PMC3509145/ /pubmed/23209676 http://dx.doi.org/10.1371/journal.pone.0050210 Text en © 2012 Grasemann 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, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Grasemann, Corinna
Devlin, Maureen J.
Rzeczkowska, Paulina A.
Herrmann, Ralf
Horsthemke, Bernhard
Hauffa, Berthold P.
Grynpas, Marc
Alm, Christina
Bouxsein, Mary L.
Palmert, Mark R.
Parental Diabetes: The Akita Mouse as a Model of the Effects of Maternal and Paternal Hyperglycemia in Wildtype Offspring
title Parental Diabetes: The Akita Mouse as a Model of the Effects of Maternal and Paternal Hyperglycemia in Wildtype Offspring
title_full Parental Diabetes: The Akita Mouse as a Model of the Effects of Maternal and Paternal Hyperglycemia in Wildtype Offspring
title_fullStr Parental Diabetes: The Akita Mouse as a Model of the Effects of Maternal and Paternal Hyperglycemia in Wildtype Offspring
title_full_unstemmed Parental Diabetes: The Akita Mouse as a Model of the Effects of Maternal and Paternal Hyperglycemia in Wildtype Offspring
title_short Parental Diabetes: The Akita Mouse as a Model of the Effects of Maternal and Paternal Hyperglycemia in Wildtype Offspring
title_sort parental diabetes: the akita mouse as a model of the effects of maternal and paternal hyperglycemia in wildtype offspring
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3509145/
https://www.ncbi.nlm.nih.gov/pubmed/23209676
http://dx.doi.org/10.1371/journal.pone.0050210
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