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Male obesity impacts DNA methylation reprogramming in sperm
BACKGROUND: Male obesity has profound effects on morbidity and mortality, but relatively little is known about the impact of obesity on gametes and the potential for adverse effects of male obesity to be passed to the next generation. DNA methylation contributes to gene regulation and is erased and...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831195/ https://www.ncbi.nlm.nih.gov/pubmed/33494820 http://dx.doi.org/10.1186/s13148-020-00997-0 |
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author | Keyhan, Sanaz Burke, Emily Schrott, Rose Huang, Zhiqing Grenier, Carole Price, Thomas Raburn, Doug Corcoran, David L. Soubry, Adelheid Hoyo, Catherine Murphy, Susan K. |
author_facet | Keyhan, Sanaz Burke, Emily Schrott, Rose Huang, Zhiqing Grenier, Carole Price, Thomas Raburn, Doug Corcoran, David L. Soubry, Adelheid Hoyo, Catherine Murphy, Susan K. |
author_sort | Keyhan, Sanaz |
collection | PubMed |
description | BACKGROUND: Male obesity has profound effects on morbidity and mortality, but relatively little is known about the impact of obesity on gametes and the potential for adverse effects of male obesity to be passed to the next generation. DNA methylation contributes to gene regulation and is erased and re-established during gametogenesis. Throughout post-pubertal spermatogenesis, there are continual needs to both maintain established methylation and complete DNA methylation programming, even during epididymal maturation. This dynamic epigenetic landscape may confer increased vulnerability to environmental influences, including the obesogenic environment, that could disrupt reprogramming fidelity. Here we conducted an exploratory analysis that showed that overweight/obesity (n = 20) is associated with differences in mature spermatozoa DNA methylation profiles relative to controls with normal BMI (n = 47). RESULTS: We identified 3264 CpG sites in human sperm that are significantly associated with BMI (p < 0.05) using Infinium HumanMethylation450 BeadChips. These CpG sites were significantly overrepresented among genes involved in transcriptional regulation and misregulation in cancer, nervous system development, and stem cell pluripotency. Analysis of individual sperm using bisulfite sequencing of cloned alleles revealed that the methylation differences are present in a subset of sperm rather than being randomly distributed across all sperm. CONCLUSIONS: Male obesity is associated with altered sperm DNA methylation profiles that appear to affect reprogramming fidelity in a subset of sperm, suggestive of an influence on the spermatogonia. Further work is required to determine the potential heritability of these DNA methylation alterations. If heritable, these changes have the potential to impede normal development. |
format | Online Article Text |
id | pubmed-7831195 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-78311952021-01-26 Male obesity impacts DNA methylation reprogramming in sperm Keyhan, Sanaz Burke, Emily Schrott, Rose Huang, Zhiqing Grenier, Carole Price, Thomas Raburn, Doug Corcoran, David L. Soubry, Adelheid Hoyo, Catherine Murphy, Susan K. Clin Epigenetics Research BACKGROUND: Male obesity has profound effects on morbidity and mortality, but relatively little is known about the impact of obesity on gametes and the potential for adverse effects of male obesity to be passed to the next generation. DNA methylation contributes to gene regulation and is erased and re-established during gametogenesis. Throughout post-pubertal spermatogenesis, there are continual needs to both maintain established methylation and complete DNA methylation programming, even during epididymal maturation. This dynamic epigenetic landscape may confer increased vulnerability to environmental influences, including the obesogenic environment, that could disrupt reprogramming fidelity. Here we conducted an exploratory analysis that showed that overweight/obesity (n = 20) is associated with differences in mature spermatozoa DNA methylation profiles relative to controls with normal BMI (n = 47). RESULTS: We identified 3264 CpG sites in human sperm that are significantly associated with BMI (p < 0.05) using Infinium HumanMethylation450 BeadChips. These CpG sites were significantly overrepresented among genes involved in transcriptional regulation and misregulation in cancer, nervous system development, and stem cell pluripotency. Analysis of individual sperm using bisulfite sequencing of cloned alleles revealed that the methylation differences are present in a subset of sperm rather than being randomly distributed across all sperm. CONCLUSIONS: Male obesity is associated with altered sperm DNA methylation profiles that appear to affect reprogramming fidelity in a subset of sperm, suggestive of an influence on the spermatogonia. Further work is required to determine the potential heritability of these DNA methylation alterations. If heritable, these changes have the potential to impede normal development. BioMed Central 2021-01-25 /pmc/articles/PMC7831195/ /pubmed/33494820 http://dx.doi.org/10.1186/s13148-020-00997-0 Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Keyhan, Sanaz Burke, Emily Schrott, Rose Huang, Zhiqing Grenier, Carole Price, Thomas Raburn, Doug Corcoran, David L. Soubry, Adelheid Hoyo, Catherine Murphy, Susan K. Male obesity impacts DNA methylation reprogramming in sperm |
title | Male obesity impacts DNA methylation reprogramming in sperm |
title_full | Male obesity impacts DNA methylation reprogramming in sperm |
title_fullStr | Male obesity impacts DNA methylation reprogramming in sperm |
title_full_unstemmed | Male obesity impacts DNA methylation reprogramming in sperm |
title_short | Male obesity impacts DNA methylation reprogramming in sperm |
title_sort | male obesity impacts dna methylation reprogramming in sperm |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7831195/ https://www.ncbi.nlm.nih.gov/pubmed/33494820 http://dx.doi.org/10.1186/s13148-020-00997-0 |
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