Andrologie

, Volume 14, Issue 1, pp 52–57

Age paternel et risques pour la descendance

  • Maurice Auroux
Vieillissement et Reproduction Vieillissement et Descendance

Resume

L’âge auquel le mâle se reproduit peut influer sur la qualité de sa descendance. Chez l’homme, le vieillissement paternel peut augmenter le risque des avortements spontanés à répétition, celui des aneuploïdies qui conduisent au syndrome XXY ou, avec une plus faible probabilité, à la Trisomie 21, le risque d’apparition de syndromes autosomiques dominants (SAD) et celui de certaines mutations récessives liées au sexe. Il semble, en outre, être responsable d’une diminution de la longévité des filles. Le vieillissement du père, mais aussi son très jeune âge, s’accompagneraient d’une augmentation des risques de malformations cardiaques et nerveuses et, chez l’animal et l’homme, d’une diminution des fonctions cognitives de la progéniture.

En ce qui concerne le vieillissement, les anomalies pourraient succéder à des mutations liées à des erreurs de recopiage du message génétique lors des phases de multiplication des spermatogonies, dont le nombre précédant la formation d’un spermatozoïde augmente avec l’âge. Une moins grande efficacité des systèmes réparateurs de l’ADN et/ou des contrôles méiotiques de la spermatogenèse pourraient également être mise en cause. A côté des mutations, le vieillissement du mâle entraînerait aussi une hyperméthylation de l’ADN ribosomal des spermatozoïdes, éventuellement préjudiciable au conceptus. Les anomalies liées au très jeune âge paternel pourraient être dues à un défaut de maturation du message génétique.

Des études statistiques suggèrent que d’autres facteurs, en particulier maternels, joueraient un rôle dans la genèse de quelques unes de ces anomalies, mais la biologie moléculaire démontre l’origine essentiellement paternelle de certains SAD, tels que le rétinoblastome bilatéral et le syndrome d’Apert. Quoi qu’il en soit, l’ensemble de ces données soulèvent, en regard de celui de la maternité, le problème, pour la descendance, de l’âge optimal de la paternité.

Mots-clés

âge paternel génome du spermatozoïde mutations facteurs épigénétiques risques pour la progéniture 

Paternal age and risks for offspring

Abstract

The age at which a male procreates can affect the quality of his offspring. In man, paternal ageing can increase: a) the risk of recurrent spontaneous abortion; b) the risk of aneuploidy responsible for Klinefelter’s syndrome and, with a lower probability, Down syndrome; c) the risk of autosomal dominant mutations, about 25 of which have been identified at the present time and which cause:-various malformations, such as Apert, Marfan, Crouzon syndromes…- tumours, such as Wilms’ tumour, bilateral retinoblastoma, von Recklinghausen’s neurofibromatosis…-metabolic changes, causing retinitis pigmentosa, fibrodysplasia ossificans progressiva, Costello and Lesch-Nyhan syndromes…- neurophysiological disorders, such as athetoid dystonic cerebral palsy, and psychotic disorders, such as schizophrenia, d) certain X-linked recessive mutations, such as haemophilia A and Duchenne’s muscular dystrophy. Paternal age also appears to lower the life expectancy of daughters. Finally, the offspring of ageing men but also very young males appear to have an increased risk of heart and nervous malformation involving autosomal dominant mutations and, in man and in animals, an impaired level of cognitive functioning of the offspring.

The abnormalities related to paternal ageing could be due to mutations linked to errors of recopying of the genetic message during spermatogonia replications, especially as the number of replications preceding the formation of spermatozoa increases with age. Decreased efficacy of DNA repair systems and/or in meiotic controls of spermatogenesis could also be involved. In addition to mutations, the ageing male also presents hypermethylation of ribosomal DNA in spermatozoa, which could be harmful for the conceptus. Abnormalities linked to a very young paternal age could be due to a defect of maturation of the genetic message via epigenetic events, such as imprinting and a cytoplasmic influence.

Some statistical studies suggest that other factors, particularly maternal factors, could also play a role in the pathogenesis of some of these abnormalities. However, molecular biology demonstrates the essentially paternal origin of certain autosomal dominant mutations, such as bilateral retinoblastoma and Apert syndrome. These data raise the problem of the optimum age for fatherhood, like that of motherhood, for the offspring.

Key-Words

paternal age spermatozoon genome mutations epigenetic factors risks for offspring 

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Copyright information

© Societe D’Andrologie De Langue Francaise 2004

Authors and Affiliations

  • Maurice Auroux
    • 1
  1. 1.Andrologie et Biologie de la ProcréationCHU de BicêtreLe Kremlin-BicêtreFrance

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