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Role of epigenetics in the etiology of hypospadias through penile foreskin DNA methylation alterations

Abnormal penile foreskin development in hypospadias is the most frequent genital malformation in male children, which has increased dramatically in recent decades. A number of environmental factors have been shown to be associated with hypospadias development. The current study investigated the role...

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Autores principales: Kaefer, Martin, Rink, Richard, Misseri, Rosalia, Winchester, Paul, Proctor, Cathy, Ben Maamar, Millissia, Beck, Daniel, Nilsson, Eric, Skinner, Michael K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9834259/
https://www.ncbi.nlm.nih.gov/pubmed/36631595
http://dx.doi.org/10.1038/s41598-023-27763-5
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author Kaefer, Martin
Rink, Richard
Misseri, Rosalia
Winchester, Paul
Proctor, Cathy
Ben Maamar, Millissia
Beck, Daniel
Nilsson, Eric
Skinner, Michael K.
author_facet Kaefer, Martin
Rink, Richard
Misseri, Rosalia
Winchester, Paul
Proctor, Cathy
Ben Maamar, Millissia
Beck, Daniel
Nilsson, Eric
Skinner, Michael K.
author_sort Kaefer, Martin
collection PubMed
description Abnormal penile foreskin development in hypospadias is the most frequent genital malformation in male children, which has increased dramatically in recent decades. A number of environmental factors have been shown to be associated with hypospadias development. The current study investigated the role of epigenetics in the etiology of hypospadias and compared mild (distal), moderate (mid shaft), and severe (proximal) hypospadias. Penile foreskin samples were collected from hypospadias and non-hypospadias individuals to identify alterations in DNA methylation associated with hypospadias. Dramatic numbers of differential DNA methylation regions (DMRs) were observed in the mild hypospadias, with reduced numbers in moderate and low numbers in severe hypospadias. Atresia (cell loss) of the principal foreskin fibroblast is suspected to be a component of the disease etiology. A genome-wide (> 95%) epigenetic analysis was used and the genomic features of the DMRs identified. The DMR associated genes identified a number of novel hypospadias associated genes and pathways, as well as genes and networks known to be involved in hypospadias etiology. Observations demonstrate altered DNA methylation sites in penile foreskin is a component of hypospadias etiology. In addition, a potential role of environmental epigenetics and epigenetic inheritance in hypospadias disease etiology is suggested.
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spelling pubmed-98342592023-01-13 Role of epigenetics in the etiology of hypospadias through penile foreskin DNA methylation alterations Kaefer, Martin Rink, Richard Misseri, Rosalia Winchester, Paul Proctor, Cathy Ben Maamar, Millissia Beck, Daniel Nilsson, Eric Skinner, Michael K. Sci Rep Article Abnormal penile foreskin development in hypospadias is the most frequent genital malformation in male children, which has increased dramatically in recent decades. A number of environmental factors have been shown to be associated with hypospadias development. The current study investigated the role of epigenetics in the etiology of hypospadias and compared mild (distal), moderate (mid shaft), and severe (proximal) hypospadias. Penile foreskin samples were collected from hypospadias and non-hypospadias individuals to identify alterations in DNA methylation associated with hypospadias. Dramatic numbers of differential DNA methylation regions (DMRs) were observed in the mild hypospadias, with reduced numbers in moderate and low numbers in severe hypospadias. Atresia (cell loss) of the principal foreskin fibroblast is suspected to be a component of the disease etiology. A genome-wide (> 95%) epigenetic analysis was used and the genomic features of the DMRs identified. The DMR associated genes identified a number of novel hypospadias associated genes and pathways, as well as genes and networks known to be involved in hypospadias etiology. Observations demonstrate altered DNA methylation sites in penile foreskin is a component of hypospadias etiology. In addition, a potential role of environmental epigenetics and epigenetic inheritance in hypospadias disease etiology is suggested. Nature Publishing Group UK 2023-01-11 /pmc/articles/PMC9834259/ /pubmed/36631595 http://dx.doi.org/10.1038/s41598-023-27763-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This 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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Kaefer, Martin
Rink, Richard
Misseri, Rosalia
Winchester, Paul
Proctor, Cathy
Ben Maamar, Millissia
Beck, Daniel
Nilsson, Eric
Skinner, Michael K.
Role of epigenetics in the etiology of hypospadias through penile foreskin DNA methylation alterations
title Role of epigenetics in the etiology of hypospadias through penile foreskin DNA methylation alterations
title_full Role of epigenetics in the etiology of hypospadias through penile foreskin DNA methylation alterations
title_fullStr Role of epigenetics in the etiology of hypospadias through penile foreskin DNA methylation alterations
title_full_unstemmed Role of epigenetics in the etiology of hypospadias through penile foreskin DNA methylation alterations
title_short Role of epigenetics in the etiology of hypospadias through penile foreskin DNA methylation alterations
title_sort role of epigenetics in the etiology of hypospadias through penile foreskin dna methylation alterations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9834259/
https://www.ncbi.nlm.nih.gov/pubmed/36631595
http://dx.doi.org/10.1038/s41598-023-27763-5
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