Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783597987877879808 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7576283 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT laurentinosandra agermcellspecificageingpatterninotherwisehealthymen AT cremersjannfrederik agermcellspecificageingpatterninotherwisehealthymen AT horsthemkebernhard agermcellspecificageingpatterninotherwisehealthymen AT tuttelmannfrank agermcellspecificageingpatterninotherwisehealthymen AT czelothkaren agermcellspecificageingpatterninotherwisehealthymen AT zitzmannmichael agermcellspecificageingpatterninotherwisehealthymen AT pohleva agermcellspecificageingpatterninotherwisehealthymen AT rahmannsven agermcellspecificageingpatterninotherwisehealthymen AT schroderchristopher agermcellspecificageingpatterninotherwisehealthymen AT berressven agermcellspecificageingpatterninotherwisehealthymen AT redmannklaus agermcellspecificageingpatterninotherwisehealthymen AT krallmannclaudia agermcellspecificageingpatterninotherwisehealthymen AT schlattstefan agermcellspecificageingpatterninotherwisehealthymen AT klieschsabine agermcellspecificageingpatterninotherwisehealthymen AT gromolljorg agermcellspecificageingpatterninotherwisehealthymen AT laurentinosandra germcellspecificageingpatterninotherwisehealthymen AT cremersjannfrederik germcellspecificageingpatterninotherwisehealthymen AT horsthemkebernhard germcellspecificageingpatterninotherwisehealthymen AT tuttelmannfrank germcellspecificageingpatterninotherwisehealthymen AT czelothkaren germcellspecificageingpatterninotherwisehealthymen AT zitzmannmichael germcellspecificageingpatterninotherwisehealthymen AT pohleva germcellspecificageingpatterninotherwisehealthymen AT rahmannsven germcellspecificageingpatterninotherwisehealthymen AT schroderchristopher germcellspecificageingpatterninotherwisehealthymen AT berressven germcellspecificageingpatterninotherwisehealthymen AT redmannklaus germcellspecificageingpatterninotherwisehealthymen AT krallmannclaudia germcellspecificageingpatterninotherwisehealthymen AT schlattstefan germcellspecificageingpatterninotherwisehealthymen AT klieschsabine germcellspecificageingpatterninotherwisehealthymen AT gromolljorg germcellspecificageingpatterninotherwisehealthymen |