Open AccessA germ cell‐specific ageing pattern in otherwise healthy men
Author(s) -
Laurentino Sandra,
Cremers JannFrederik,
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
Publication year - 2020
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.13242
Subject(s) - biology , ageing , germ cell , sperm , fecundity , germline , offspring , fertility , dna methylation , andrology , somatic cell , genetics , male infertility , spermatogenesis , epigenetics , physiology , infertility , gene , endocrinology , pregnancy , gene expression , population , demography , medicine , sociology
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.