Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Keyhan, Sanaz, Burke, Emily, Schrott, Rose, Huang, Zhiqing, Grenier, Carole, Price, Thomas, Raburn, Doug, Corcoran, David L., Soubry, Adelheid, Hoyo, Catherine, Murphy, Susan K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
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
_version_ 1783641585314955264
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
work_keys_str_mv AT keyhansanaz maleobesityimpactsdnamethylationreprogramminginsperm
AT burkeemily maleobesityimpactsdnamethylationreprogramminginsperm
AT schrottrose maleobesityimpactsdnamethylationreprogramminginsperm
AT huangzhiqing maleobesityimpactsdnamethylationreprogramminginsperm
AT greniercarole maleobesityimpactsdnamethylationreprogramminginsperm
AT pricethomas maleobesityimpactsdnamethylationreprogramminginsperm
AT raburndoug maleobesityimpactsdnamethylationreprogramminginsperm
AT corcorandavidl maleobesityimpactsdnamethylationreprogramminginsperm
AT soubryadelheid maleobesityimpactsdnamethylationreprogramminginsperm
AT hoyocatherine maleobesityimpactsdnamethylationreprogramminginsperm
AT murphysusank maleobesityimpactsdnamethylationreprogramminginsperm