Aging and Male Fertility

In 1912, Weinberg noted that the skeletal disorder achondroplasia was prominent in younger rather than older siblings; he was the first to suggest the possible link between paternal age and genetic diseases in offspring [4]. Thus, despite the ability of men to father children well into old age, there appears to be a positive relationship between paternal age and genetic disease in their offspring [50]. Older men have greater difficulties in achieving full-term pregnancy with their partners; increasing paternal age is associated with a reduction in the quality of spermatozoa, i.e., decline in sperm motility and morphology [51] and a higher incidence of DNA fragmentation [52]; there are inconsistent reports as to whether, in man, there is a decline in sperm production rate with advancing age [53]. However, fathers over 40 have both a greater difficulty to conceive [54-56] and their partners have a higher miscarriage rate [57]. With respect to genetic diseases, increased incidences of disorders such as Apert syndrome [58], Marfan syndrome, and achondroplasia [50, 59] have been linked to paternal aging. In addition, several other diseases of complex etiology have been associated with a paternal age effect; these include schizophrenia [60], Alzheimer's disease [61], autism [62], and cardiac defects [63], which all have increased relative risk in children born to older fathers. Spontaneous mutation frequency in pachytene spermatocytes, round spermatids, and caudal spermatozoa is elevated in aged mice, and 80% of these mutations are characterized as single base substitutions [64]. There is an increased rate of basal sperm chromatin damage and a decreased ability to respond to external oxidative stress as rats age [65] . Thus, there appears to be an accumulation of DNA damage and/or mutations in the germ line as men age and this affects the health and wellbeing of their offspring. Studies using mouse and rat animal models have further substantiated the link between paternal age and adverse effects on progeny outcome.

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100 Pregnancy Tips

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