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A germ cell‐specific ageing pattern in otherwise healthy men

Life‐long sperm production leads to the assumption that male fecundity remains unchanged throughout life. However, recently it was shown that paternal age has profound consequences for male fertility and offspring health. Paternal age effects are caused by an accumulation of germ cell mutations over...

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Autores principales: Laurentino, Sandra, Cremers, Jann‐Frederik, Horsthemke, Bernhard, Tüttelmann, Frank, Czeloth, Karen, Zitzmann, Michael, Pohl, Eva, Rahmann, Sven, Schröder, Christopher, Berres, Sven, Redmann, Klaus, Krallmann, Claudia, Schlatt, Stefan, Kliesch, Sabine, Gromoll, Jörg
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576283/
https://www.ncbi.nlm.nih.gov/pubmed/32951333
http://dx.doi.org/10.1111/acel.13242
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author Laurentino, Sandra
Cremers, Jann‐Frederik
Horsthemke, Bernhard
Tüttelmann, Frank
Czeloth, Karen
Zitzmann, Michael
Pohl, Eva
Rahmann, Sven
Schröder, Christopher
Berres, Sven
Redmann, Klaus
Krallmann, Claudia
Schlatt, Stefan
Kliesch, Sabine
Gromoll, Jörg
author_facet Laurentino, Sandra
Cremers, Jann‐Frederik
Horsthemke, Bernhard
Tüttelmann, Frank
Czeloth, Karen
Zitzmann, Michael
Pohl, Eva
Rahmann, Sven
Schröder, Christopher
Berres, Sven
Redmann, Klaus
Krallmann, Claudia
Schlatt, Stefan
Kliesch, Sabine
Gromoll, Jörg
author_sort Laurentino, Sandra
collection PubMed
description Life‐long sperm production leads to the assumption that male fecundity remains unchanged throughout life. However, recently it was shown that paternal age has profound consequences for male fertility and offspring health. Paternal age effects are caused by an accumulation of germ cell mutations over time, causing severe congenital diseases. Apart from these well‐described cases, molecular patterns of ageing in germ cells and their impact on DNA integrity have not been studied in detail. In this study, we aimed to assess the effects of ‘pure’ ageing on male reproductive health and germ cell quality. We assembled a cohort of 198 healthy men (18–84 years) for which end points such as semen and hormone profiles, sexual health and well‐being, and sperm DNA parameters were evaluated. Sperm production and hormonal profiles were maintained at physiological levels over a period of six decades. In contrast, we identified a germ cell‐specific ageing pattern characterized by a steady increase of telomere length in sperm and a sharp increase in sperm DNA instability, particularly after the sixth decade. Importantly, we found sperm DNA methylation changes in 236 regions, mostly nearby genes associated with neuronal development. By in silico analysis, we found that 10 of these regions are located in loci which can potentially escape the first wave of genome‐wide demethylation after fertilization. In conclusion, human male germ cells present a unique germline‐specific ageing process, which likely results in diminished fecundity in elderly men and poorer health prognosis for their offspring.
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spelling pubmed-75762832020-10-23 A germ cell‐specific ageing pattern in otherwise healthy men Laurentino, Sandra Cremers, Jann‐Frederik Horsthemke, Bernhard Tüttelmann, Frank Czeloth, Karen Zitzmann, Michael Pohl, Eva Rahmann, Sven Schröder, Christopher Berres, Sven Redmann, Klaus Krallmann, Claudia Schlatt, Stefan Kliesch, Sabine Gromoll, Jörg Aging Cell Original Articles Life‐long sperm production leads to the assumption that male fecundity remains unchanged throughout life. However, recently it was shown that paternal age has profound consequences for male fertility and offspring health. Paternal age effects are caused by an accumulation of germ cell mutations over time, causing severe congenital diseases. Apart from these well‐described cases, molecular patterns of ageing in germ cells and their impact on DNA integrity have not been studied in detail. In this study, we aimed to assess the effects of ‘pure’ ageing on male reproductive health and germ cell quality. We assembled a cohort of 198 healthy men (18–84 years) for which end points such as semen and hormone profiles, sexual health and well‐being, and sperm DNA parameters were evaluated. Sperm production and hormonal profiles were maintained at physiological levels over a period of six decades. In contrast, we identified a germ cell‐specific ageing pattern characterized by a steady increase of telomere length in sperm and a sharp increase in sperm DNA instability, particularly after the sixth decade. Importantly, we found sperm DNA methylation changes in 236 regions, mostly nearby genes associated with neuronal development. By in silico analysis, we found that 10 of these regions are located in loci which can potentially escape the first wave of genome‐wide demethylation after fertilization. In conclusion, human male germ cells present a unique germline‐specific ageing process, which likely results in diminished fecundity in elderly men and poorer health prognosis for their offspring. John Wiley and Sons Inc. 2020-09-20 2020-10 /pmc/articles/PMC7576283/ /pubmed/32951333 http://dx.doi.org/10.1111/acel.13242 Text en © 2020 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Laurentino, Sandra
Cremers, Jann‐Frederik
Horsthemke, Bernhard
Tüttelmann, Frank
Czeloth, Karen
Zitzmann, Michael
Pohl, Eva
Rahmann, Sven
Schröder, Christopher
Berres, Sven
Redmann, Klaus
Krallmann, Claudia
Schlatt, Stefan
Kliesch, Sabine
Gromoll, Jörg
A germ cell‐specific ageing pattern in otherwise healthy men
title A germ cell‐specific ageing pattern in otherwise healthy men
title_full A germ cell‐specific ageing pattern in otherwise healthy men
title_fullStr A germ cell‐specific ageing pattern in otherwise healthy men
title_full_unstemmed A germ cell‐specific ageing pattern in otherwise healthy men
title_short A germ cell‐specific ageing pattern in otherwise healthy men
title_sort germ cell‐specific ageing pattern in otherwise healthy men
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576283/
https://www.ncbi.nlm.nih.gov/pubmed/32951333
http://dx.doi.org/10.1111/acel.13242
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