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.
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.
Article PDF
References
ASHWOOD-SMITH M.J., EDWARDS R.G.: DNA repair by ovocytes. Mol. Hum. Reprod., 1996, 2: 46–51.
AUROUX M.: Decrease of learning capacity in offspring with increasing paternal age in the rat. Teratology, 1983, 27: 141–148.
AUROUX M.: Age paternel et descendance. Andrologie, 2000, 2: 155–165.
AUROUX M.R., DULIOUST E.M., NAWAR N.Y., YACOUB S.G., KEMPF E.H., EBEL A.B.: Cyclophosphamide in the male rat: cerebral biochemical changes in progeny. Biomed. Pharmacother., 1990, 44: 519–523.
AUROUX M., DULIOUST E., SELVA J., RINCE P.: Cyclophosphamide in the F0 male rat: physical and behavioral changes in three successive adult generations. Mutat. Res., 1990, 229, 189–200.
AUROUX M., MAYAUX M.J., GUIHARD-MOSCATO M.L., FROMATIN M., BARTHE J., SCHWARTZ D.: Paternal age and mental functions of progeny in man. Hum. Reprod., 1989, 4: 794–797.
AUROUX M., NAWAR N.N.Y., NAGUIB M., BAUD M., LAPAQUELLERIE N.: Post-pubescent to mature fathers: increase in progeny quality? Hum. Reprod., 1998, 13: 55–59.
BARTON S.C., SURANI M.A.H., NORRIS M.L.: Role of paternal and maternal genome in mouse development. Nature, 1984, 311: 374–376.
BRANDRIFF B., GORDON L., ASHWORTH L. et al.: Chromosomes of human sperm: variability among normal individuals. Hum. Genet., 1985, 7: 18–24.
BURGOYNE P.S.: Sperm phenotype and its relationship to somatic and germ line genotype: a study using mouse agregation chimeras. Dev. Biol., 1975, 44: 63–76.
CAMPBELL J.H.: Automodulation of genes: explanation for lasting effects seen in functionnal neuroteratology? 15th Intern. Summer School of Brain Research: Neurochemistry of Functionnal Neuroteratology, Amsterdam, August 31 to September 4, 1987: 33.
CAMPBELL J.H., ZIMMERMANN E.G.: Automodulation of genes: a proposed mechanism for persisting effects of drugs and hormones in mammals. Neurobehav. Toxicol. Teratol., 1982, 4: 435–439.
CECOS: THEPOT F., WACK T., SELVA J., CZYGLIK F., MAYAUX M.J.: Age paternel et issues de grossesses. Expérience des CECOS. Contracept. Fertil. Sex., 1993, 21: 388–390.
CROW J.F.: The high spontaneous mutation rate: is it a health risk? Proc. Natl. Acad. Sci. USA, 1997, 94: 8380–8386.
DRISCOLL D.J., MIGEON B.R.: Sex differences in methylation of single copy gene in human meiotic germ cells: implications for X chromosome inactivation, parental imprinting and origin of CpG mutations. Somatic. Cell Mol. Genet., 1990, 16: 267–282.
DRYJA T.P., MUKAI S., PETERSEN R., RAPPAPORT J.M., WALTON D., YANDELL D.W.: Parental origin of mutations of the retinoblastoma gene. Nature, 1989, 339: 556–558.
FRIEDMAN J.M.: Genetic desease in the offspring of older fathers. Obstet. Gynecol., 1981, 57: 745–749.
GAVRILOV L.A., GAVRILOVA N.S., KROUTKO V.N. et al.: Mutation load and human longevity. Mutat. Res., 1997, 377: 61–62.
HASSOLD T.J.: The origin of non-dysjunction in humans. Meeting of the International Human Genetics Society. Washington, October 1991. In AYME S. ed. Epidémiologie de la Trisomie 21. Les données récentes. 10ème séminaire de Diagnostic Anténatal des malformations. Paris (Necker), 1991.
HOOK E.B., REGAL R.R.: A search of a paternal-age effect upon cases of 47, + 21 in wich the extra chromosome is of paternal origin. Am. J. Hum. Genet., 1984, 36: 413–421.
HOOK E.B., SCHREINEMACHERS D.M., WILLEY A.M., CROSS P.K.: Innerited structural cytogenetic abnormalities detected incidentally in fetuses diagnosed prenatally: frequency, paternal age associations, sex-ratio trends, and comparisons with rates of mutants. Am. J. Hum. Genet., 1984, 36: 422–443.
INOUE M., KURIHARA T., YAMASHITA M., TATSUNI K.: Effects of treatment with methyl methane sulfonate during meiotic and post meiotic stages and maturation of spermatozoa in mice. Mutat. Res., 1993, 294: 179–186.
KAPLAN J., TOUTAIN A.: La maladie de Recklinghausen. In 3e Semaine de Genetique Clinique: Affections dominantes à expression variable et Conseil Génétique, Paris (Necker), 1987:42–52.
KELSO K.A., REDPATH A., NOBLE R.C., SPEAK B.K.: Lipid and antioxidant changes in spermatozoa and seminal plasma throughout the reproductive period of bulls. J. Reprod. Fertil., 1997, 109: 1–6.
KRUMLAUF R.: Hox genes and pattern formation in the branchial region of the vertebrate head. Trends Genet., 1993, 9: 106–112.
LEE I.P.: Adaptative biochemical repair responses toward germ cell DNA damage. Am. J. Int. Med., 1983, 4: 135–147.
LIAN Z.H., ZACK M.M., ERICKSON J.D.: Paternal age and the occurrence of birth defects. Am. J. Hum. Genet., 1986, 39: 648–660.
LOWE X., ESKENAZI B., NELSON D.O., KIDD S., ALME A., WYROBEK A.J.: Frequency of XY sperm increases with age in fathers of boys with Klinefelter syndrome. Am. J. Hum. Genet., 2001, 69: 1046–1054.
MARTIN R.H., BALKAN W., BURNS K., RADEMAKER A.W., LIN C.C., RUDD N.L.: The chromosome constitution of 1 000 human spermatozoa. Hum. Genet., 1983, 63: 305–309.
MARTIN R.H., RADEMAKER A.W.: The effect of age on the frequency of sperm chromosomal abnormalities in normal mem. Am. J. Hum. Genet., 1987, 41: 484–492.
MATSUNAGA E., TONOMURA E., OISHI A., KIKUCHI Y.: Reexamination of paternal age effect in Down’s syndrome. Hum. Genet., 1978, 40: 259–268.
Mc INTOSH G.C., OLSHAN A.F., BAIRD P.A.: Paternal age and the risk of birth defects in offspring. Epidemiology, 1995, 6: 282–288.
MOLONEY D.M., SLANEY S.F., OLDRIDGE M. et al.: Exclusive paternal origin of new mutations in Apert syndrome. Nat. Genet., 1996, 13: 48–53.
OAKES C.C., SMIRAGLIA D.J., PLASS C., TRASLER J.M., ROBAIRE B.: Aging results in hypermethylation of ribosomal DNA in sperm and liver of male rats. Proc. Natl. Acad. Sci. USA, 2003, 100: 1775–1780.
OLSHAN A.F., SCHNITZER P.G., BAIRD P.A.: Paternal age and the risk of congenital defects. Teratology, 1994, 50: 80–84.
PENROSE L.S.: Paternal age and mutation. Lancet, 1995, II: 312–313.
REIK W., WALTER J., GURTMANN I. et al.: Imprinting in development and disease. 9th Annual meeting of European Society of Human Reproduction and Embryology, Thessanoliki, 27–30 June 1993.
RISCH N., REICH E.W., WISHNICK M.M., McCARTHY J.G.: Spontaneous mutation and parental age in humans. Am. J. Hum. Genet., 1987, 41: 218–248.
ROTH M.P., STOLL C., TAILLEMITE J.L., GIRARD S., BOUE A.: Paternal age and Down’s syndrome diagnosed prenatally: no association in French data. Prenet. Diagn., 1983, 3: 327–335.
SAPIENZA C., PETERSON A.C., ROSSANT J., BALLING R.: Degree of methylation of transgenes is dependent on gamete of origin. Nature, 1987, 328: 251–254.
SCHOTT J.J., BENSON D.W., BASSON C.T. et al.: Congenital heart disease caused by mutations in the transcription factor NKX2-5, Science, 1998, 281: 108–111.
SCHWARTZ D., MAYAUX M.J., SPIRA A. et al.: Study of a group of 484 fertile men, Part II: Relation between age (20–59) and semen characteristics. Int. J. Androl., 1981, 4: 450–456.
SELVIN S., GARFINKE G.: Paternal age, maternal age and birth order and risk of a fetal loss. Hum. Biol., 1976, 48: 223–230.
SHERMAN S.L., TAKAESU N., FREEMAN S. et al.: Trisomy 21: association between reduced recombination and non dysjunction. Am. J. Hum. Genet., 1990, 47, A 97.
STENE J., FISCHER G., STENE E., MIKKELSEN M., PETERSEN, E.: Paternal age effect in Down’s syndrome. Ann Hum. Genet., 1977, 40: 299–306.
STYLIANOS E., ANTONARAKIS M.D.: The down syndrom collaborative group. Parental origin of the extra chromosome in trisomy 21 as indicated by analysis of DNA polymorphisms. N. Engl. J. Med., 1991, 324: 872–876.
TARIN J.J., BRINES J., CANO A.: Long term effects of delayed parenthood. Hum. Reprod., 1998, 13: 2371–2376.
VOGEL F., RATHENBERG R.: Spontaneous mutation in man. Adv. Hum. Genet., 1975, 5: 223–318.
WALLACE D.C.: Mitochondrial genetics: a paradigm for aging and degenerative diseases? Sciences, 1992, 256: 628–632.
WALTER C.A., INTANO G.W., McCARREY J.R., McMAHAN C.A., WALTER R.B.: Mutation frequency declines during spermatogenesis in young mice but increases in old mice. Proc. Natl. Acad. Sci. USA, 1998, 95: 10015–10019.
Author information
Authors and Affiliations
Additional information
Communication au XXo Congrès de la Société d’Andrologie de Language Française, Orléans, 11–13 décembre 2003.
Rights and permissions
About this article
Cite this article
Auroux, M. Age paternel et risques pour la descendance. Androl. 14, 52–57 (2004). https://doi.org/10.1007/BF03035468
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF03035468