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Paternal obesity induces placental hypoxia and sex-specific impairments in placental vascularization and offspring metabolism(†)
Paternal obesity predisposes offspring to metabolic dysfunction, but the underlying mechanisms remain unclear. We investigated whether this metabolic dysfunction is associated with changes in placental vascular development and is fueled by endoplasmic reticulum (ER) stress-mediated changes in fetal...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9382389/ https://www.ncbi.nlm.nih.gov/pubmed/35377412 http://dx.doi.org/10.1093/biolre/ioac066 |
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author | Jazwiec, Patrycja A Patterson, Violet S Ribeiro, Tatiane A Yeo, Erica Kennedy, Katherine M Mathias, Paulo C F Petrik, Jim J Sloboda, Deborah M |
author_facet | Jazwiec, Patrycja A Patterson, Violet S Ribeiro, Tatiane A Yeo, Erica Kennedy, Katherine M Mathias, Paulo C F Petrik, Jim J Sloboda, Deborah M |
author_sort | Jazwiec, Patrycja A |
collection | PubMed |
description | Paternal obesity predisposes offspring to metabolic dysfunction, but the underlying mechanisms remain unclear. We investigated whether this metabolic dysfunction is associated with changes in placental vascular development and is fueled by endoplasmic reticulum (ER) stress-mediated changes in fetal hepatic development. We also determined whether paternal obesity indirectly affects the in utero environment by disrupting maternal metabolic adaptations to pregnancy. Male mice fed a standard chow or high fat diet (60%kcal fat) for 8–10 weeks were time-mated with female mice to generate pregnancies and offspring. Glucose tolerance was evaluated in dams at mid-gestation (embryonic day (E) 14.5) and late gestation (E18.5). Hypoxia, angiogenesis, endocrine function, macronutrient transport, and ER stress markers were evaluated in E14.5 and E18.5 placentae and/or fetal livers. Maternal glucose tolerance was assessed at E14.5 and E18.5. Metabolic parameters were assessed in offspring at ~60 days of age. Paternal obesity did not alter maternal glucose tolerance but induced placental hypoxia and altered placental angiogenic markers, with the most pronounced effects in female placentae. Paternal obesity increased ER stress-related protein levels (ATF6 and PERK) in the fetal liver and altered hepatic expression of gluconeogenic factors at E18.5. Offspring of obese fathers were glucose intolerant and had impaired whole-body energy metabolism, with more pronounced effects in female offspring. Metabolic deficits in offspring due to paternal obesity may be mediated by sex-specific changes in placental vessel structure and integrity that contribute to placental hypoxia and may lead to poor fetal oxygenation and impairments in fetal metabolic signaling pathways in the liver. |
format | Online Article Text |
id | pubmed-9382389 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-93823892022-08-18 Paternal obesity induces placental hypoxia and sex-specific impairments in placental vascularization and offspring metabolism(†) Jazwiec, Patrycja A Patterson, Violet S Ribeiro, Tatiane A Yeo, Erica Kennedy, Katherine M Mathias, Paulo C F Petrik, Jim J Sloboda, Deborah M Biol Reprod Research Article Paternal obesity predisposes offspring to metabolic dysfunction, but the underlying mechanisms remain unclear. We investigated whether this metabolic dysfunction is associated with changes in placental vascular development and is fueled by endoplasmic reticulum (ER) stress-mediated changes in fetal hepatic development. We also determined whether paternal obesity indirectly affects the in utero environment by disrupting maternal metabolic adaptations to pregnancy. Male mice fed a standard chow or high fat diet (60%kcal fat) for 8–10 weeks were time-mated with female mice to generate pregnancies and offspring. Glucose tolerance was evaluated in dams at mid-gestation (embryonic day (E) 14.5) and late gestation (E18.5). Hypoxia, angiogenesis, endocrine function, macronutrient transport, and ER stress markers were evaluated in E14.5 and E18.5 placentae and/or fetal livers. Maternal glucose tolerance was assessed at E14.5 and E18.5. Metabolic parameters were assessed in offspring at ~60 days of age. Paternal obesity did not alter maternal glucose tolerance but induced placental hypoxia and altered placental angiogenic markers, with the most pronounced effects in female placentae. Paternal obesity increased ER stress-related protein levels (ATF6 and PERK) in the fetal liver and altered hepatic expression of gluconeogenic factors at E18.5. Offspring of obese fathers were glucose intolerant and had impaired whole-body energy metabolism, with more pronounced effects in female offspring. Metabolic deficits in offspring due to paternal obesity may be mediated by sex-specific changes in placental vessel structure and integrity that contribute to placental hypoxia and may lead to poor fetal oxygenation and impairments in fetal metabolic signaling pathways in the liver. Oxford University Press 2022-04-04 /pmc/articles/PMC9382389/ /pubmed/35377412 http://dx.doi.org/10.1093/biolre/ioac066 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Research Article Jazwiec, Patrycja A Patterson, Violet S Ribeiro, Tatiane A Yeo, Erica Kennedy, Katherine M Mathias, Paulo C F Petrik, Jim J Sloboda, Deborah M Paternal obesity induces placental hypoxia and sex-specific impairments in placental vascularization and offspring metabolism(†) |
title | Paternal obesity induces placental hypoxia and sex-specific impairments in placental vascularization and offspring metabolism(†) |
title_full | Paternal obesity induces placental hypoxia and sex-specific impairments in placental vascularization and offspring metabolism(†) |
title_fullStr | Paternal obesity induces placental hypoxia and sex-specific impairments in placental vascularization and offspring metabolism(†) |
title_full_unstemmed | Paternal obesity induces placental hypoxia and sex-specific impairments in placental vascularization and offspring metabolism(†) |
title_short | Paternal obesity induces placental hypoxia and sex-specific impairments in placental vascularization and offspring metabolism(†) |
title_sort | paternal obesity induces placental hypoxia and sex-specific impairments in placental vascularization and offspring metabolism(†) |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9382389/ https://www.ncbi.nlm.nih.gov/pubmed/35377412 http://dx.doi.org/10.1093/biolre/ioac066 |
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