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Einfluss des Diabetes mellitus auf die Fertilität des Mannes

Ein wenig untersuchter Faktor der männlichen Infertilität

The influence of diabetes mellitus on male reproductive function

A poorly investigated aspect of male infertility

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Zusammenfassung

Der Diabetes mellitus (DM) bringt zahlreiche systemische Komplikationen mit sich. Im andrologischen Arbeitsgebiet stehen die Erektionsstörung, die retrograde Ejakulation und der Hypogonadismus im Vordergrund. Die Störung der männlichen Infertilität im Zusammenhang mit dem DM ist als solche nicht bekannt. Aufgrund der unzureichenden und teilweise nicht stimmigen Datenlage hinsichtlich der Auswirkungen dieser Erkrankung auf die Spermienqualität erachten nur wenige Fertilitätsspezialisten sie als relevant. Folglich gibt es nur wenige Informationen über ihre Prävalenz bei infertilen Männern. Aufgrund von neuen Studienergebnissen, die zeigten, dass Diabetes minimale molekulare Veränderungen induziert, die für die Spermienfunktion und -qualität wichtig sind, muss diese Einschätzung überdacht werden. Diabetische Männer weisen einen signifikant höheren Anteil von Spermien mit Kern-DNA-Schädigung (nDNA) auf, ein Faktor, der mit einer Einschränkung der Fertilität und erhöhten Fehlgeburtsraten einhergeht. Der Mechanismus, durch den diese diabetogene Spermien-nDNA-Schädigung ausgelöst wird, ist unbekannt. Die Feststellung hoher Spiegel nichtenzymatisch glykosylierter Proteine bzw. Lipide als irreversible Endprodukte („advanced glycation end products“, AGE) und ihres Rezeptors (RAGE) im ganzen männlichen Reproduktionstrakt im Zusammenhang mit Veränderungen der testikulären Metabolitenspiegel und Spermatogenese-Genexpression lassen vermuten, dass die Glykosylierung eine integrale Rolle beim oxidativen Stress spielt, der wiederum eine Spermien-nDNA-Schädigung verursacht. Da die Glykosylierung eine normale Auswirkung des Lebens ist und in die DNA-Fragmentierung verschiedener scheinbar nicht verbundener Bedingungen involviert ist, könnte sie ein allgemeiner Mechanismus für die an Spermien-DNA zu beobachtende Schädigung sein.

Abstract

Whilst diabetes mellitus is known to have many systemic complications, male infertility, beyond impotence, retrograde ejaculation and hypogonadism, has not been widely recognised to be one of them. Due to the paucity of studies and inconsistencies regarding the condition’s impact on semen quality, few fertility specialists consider the condition noteworthy. As a consequence little information exists as to its prevalence amongst infertile men. Recently the prevailing view has been challenged by findings showing that diabetes induces subtle molecular changes that are important for sperm quality and function. Diabetic men have been found to have a significantly higher percentage of sperm with nuclear DNA damage, a factor known to be associated with compromised fertility and increased miscarriage rates. The mechanism by which this diabetes-related sperm nDNA damage occurs remains unknown. The identification of high levels of advanced glycation end products (AGEs) and their receptor (RAGE) throughout the male reproductive tract coupled to changes in testicular metabolite levels and spermatogenic gene expression suggest that glycation may play an integral role in oxidative stress which in turn causes sperm nDNA damage. As glycation is a normal consequence of life and has been implicated in DNA fragmentation in a variety of seemingly unconnected conditions, it may constitute a common mechanism for the damage seen in sperm DNA.

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Authors and Affiliations

  1. Centrum für Reproduktionsmedizin und Andrologie, Universität Münster, Domagkstraße 11, 48149, Münster, Deutschland

    C. Mallidis & S. Kliesch

  2. Regional Fertility Centre, Royal Maternity Hospital, Belfast, UK

    I. Agbaje & N. McClure

  3. Obstetrics and Gynaecology, Queen’s University Belfast, Belfast, UK

    N. McClure

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  1. C. Mallidis
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  2. I. Agbaje
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  3. N. McClure
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  4. S. Kliesch
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Correspondence to C. Mallidis.

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Mallidis, C., Agbaje, I., McClure, N. et al. Einfluss des Diabetes mellitus auf die Fertilität des Mannes. Urologe 50, 33–37 (2011). https://doi.org/10.1007/s00120-010-2440-3

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