A germ cell‐specific ageing pattern in otherwise healthy men (09/2020)

Laurentino S, Cremers JF, Horsthemke B, Tüttelmann F, Czeloth K, Zitzmann M, Pohl E, Rahmann S, Schröder C, Berres S, Redmann K, Krallmann C, Schlatt S, Kliesch S, Gromoll J

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. However, molecular patterns of ageing in germ cells and their impact on DNA integrity have not been studied in detail. 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) and evaluated a variety of end points. While sperm production and hormonal profiles were maintained at physiological levels over a period of six decades, we identified a steady increase of telomere length in sperm, a sharp increase in sperm DNA instability and sperm DNA methylation changes in 236 regions. 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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Does the FSHB c.-211G greater than T polymorphism impact Sertoli cell number and the spermatogenic potential in infertile patients? (02/2020)

Maria Schubert, Sophie Kaldewey, Lina Pérez Lanuza, Henrike Krenz, Martin Dugas, Sven Berres, Sabine Kliesch, Joachim Wistuba, Jörg Gromoll
(Schubert et al., 2020)

Our group is working on the impact  of c.-211G>T FSHB single nucleotide polymorphism (SNP) on spermatogenesis. We and others have recently shown that this SNP is strongly associated with lowered testicular volume, reduced sperm counts and decreased FSH levels in patients carrying one or two T-alleles. However it was  not clear to which extent Sertoli cell (SC) number, Sertoli cell workload (SCWL) and thereby spermatogenic potential is affected. In the current study we demonstrated that neither SC number nor SCWL is significantly different among different genotypes of the -211G>T FSHB SNP (see figure). Thus the spermatogenic potential is maintained independent of the SNP genotype.  The previously observed clinical phenotype might be caused by a hypo-stimulated spermatogenesis and not due to a decreased SC number. Our findings support the concept for a putative treatment of infertile men with FSH to stimulate spermatogenesis further.

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Stem cell–based options to preserve male fertility (03/2019)

Nina Neuhaus and Stefan Schlatt

Pediatric gonadotoxic treatments like cancer treatment can cause subfertility or even permanent infertility. While adult men can cryopreserve sperm as fertility reserve, this strategy cannot be applied for prepubertal patients. In this article Nina Neuhaus and Stefan Schlatt give a perspective on stem cell-based options to preserve male fertility.

Science  22 Mar 2019: Vol. 363, Issue 6433, pp. 1283-1284; DOI:10.1126/science.aaw6927
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The human RHOX gene cluster: target genes and functional analysis of gene variants in infertile men (11/2016)

Jennifer Borgmann, Frank Tüttelmann, Bernd Dworniczak, Albrecht Röpke, Hye-Won Song, Sabine Kliesch, Miles F Wilkinson, Sandra Laurentino, Jörg Gromoll
Location of identified mutations within the RHOX gene structure. Non-synonymous mutations are indicated in bold, the characteristic RHOX DNA-binding domain (termed homeodomain) is shown in black and the identified mutations are marked with red arrows (adapted from Borgmann et al., 2016).

"RHOX transcription factor genes are mutated in infertile men"

Infertility affects 10-15% of couples with the wish for parenthood, and nearly half of these cases can be attributed to a male factor. That means around 7 percent of all males of reproductive age have fertility problems. In a collaborative study, recently published by Human Molecular Genetics, the researchers provide evidence that mutations in the reproductive homeobox (RHOX) family of transcription factors are linked to infertile men with severely low sperm count.

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The CatSper channel mediates progesterone-induced Ca2+ influx in human sperm (03/2011)

Timo Strünker, Normann Goodwin, Christoph Brenker, Ingo Weyand, Reinhard Seifert, U. Benjamin Kaupp

How do sperm find their way to the egg? It has been proposed that chemotaxis, hyperactivation and acrosomal exocytosis of sperm is controlled by a Ca2+ signal. The underlying signalling mechanism is investigated in this study. It is shown that progesterone activates the sperm specific, pH-sensitive CatSper Ca2+ channel which in turn leads to rapid Ca2+ influx.

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