The Influence of Paternal Age on Down Syndrome

Fisch, Harry; Hyun, Grace; Golden, Richard M.; Hensle, Terry W.; Olsson, Carl A.; Liberson, Gary

doi:10.1097/01.ju.0000067958.36077.d8

Cited by 117 publications

(76 citation statements)

References 17 publications

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“…Recently, many reports suggested a clear relationship between paternal age and diverse pathologies in offspring such as autism, schizophrenia and Down's syndrome [Fisch et al 2003;Malaspina et al 2001;Reichenberg et al 2006]. Others proposed a link between the age of the father and miscarriage [Kleinhaus et al 2006].…”

Section: Discussionmentioning

confidence: 99%

Spermiogenesis and DNA Repair: A Possible Etiology of Human Infertility and Genetic Disorders

Leduc¹,

Nkoma²,

Boissonneault³

2008

Systems Biology in Reproductive Medicine

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This paper reviews the possible origin of sperm DNA fragmentation and focuses on the nuclear events associated with spermiogenesis as a potential source of genetic instability and reduced fertilizing potential of the mature male gamete. Recent findings suggest a programmed DNA fragmentation and DNA damage response during the chromatin remodeling steps in spermatids. We also discuss the spermatid DNA repair mechanisms and the possible involvement of condensing proteins, such as transition proteins and protamines, in the process, as this DNA fragmentation is normally not found in late spermatids. We propose that alterations in the chromatin remodeling steps or DNA repair in elongating spermatids may lead to persistent DNA breaks. This vulnerable step of spermiogenesis may provide a clue to the etiology of sperm DNA fragmentation associated with infertility in humans. This vulnerability is further emphasized given the haploid character of spermatids that must resolve programmed double-stranded breaks by an error-prone DNA repair mechanism. Therefore, spermiogenesis has probably been overlooked as an important source of genetic instability.

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Section: Discussionmentioning

confidence: 99%

Spermiogenesis and DNA Repair: A Possible Etiology of Human Infertility and Genetic Disorders

Leduc¹,

Nkoma²,

Boissonneault³

2008

Systems Biology in Reproductive Medicine

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“…A recent evaluation of 3419 affected subjects, however, revealed that trisomy 21 and higher paternal age are only associated when mothers are aged 35 years or older. The paternal contribution to Down syndrome reached 50% when the mother was 40 or older (Fisch et al, 2003). But as only about 22% of all trisomies 21 survive to term and as the excess chromosome 21 originates from the father in only 5-10% (Hassold and Sherman, 2000), the risk for children of aged fathers still remains very low.…”

Section: Aneuploidiesmentioning

confidence: 99%

Paternal age and reproduction

Sartorius

Nieschlag

2009

Human Reproduction Update

286

210

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background: Due to various sociological factors, couples in developed countries are increasingly delaying childbearing. Besides ethical, economical and sociological issues, this trend presents us with several complex problems in reproduction. Although it is well-known that maternal age has a negative effect on fertility and increases the risk of adverse outcome during pregnancy and in offspring, the paternal influence on these outcomes is less well researched and not well-known.methods: We performed a systematic search of PubMed, and retrieved original articles and review articles to update our previous survey in this journal.results: This review highlights the link between male age and genetic abnormalities in the germ line and summarizes the knowledge about the effects of paternal age on reproductive function and outcome. Increasing paternal age can be associated with decreasing androgen levels, decreased sexual activity, alterations of testicular morphology and a deterioration of semen quality (volume, motility, morphology). Increased paternal age has an influence on DNA integrity of sperm, increases telomere length in spermatozoa and is suggested to have epigenetic effects. These changes may, at least in part, be responsible for the association of paternal age over 40 years with reduced fertility, an increase in pregnancy-associated complications and adverse outcome in the offspring. conclusion: Although higher maternal age can be an indication for intensive prenatal diagnosis, including invasive diagnostics, consideration of the available evidence suggests that paternal age itself, however, provides no rationale for invasive procedures.

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“…45 A similar influence of paternal age on the risk of having a child with Down's syndrome has also been reported, and paternal age was a factor in half of the cases of Down's syndrome when the maternal age exceeded 35 years. 46 Other investigators found that the rate of miscarriages increased with advancing paternal age when the maternal age was more than 35 years. 30 Thus, there is convincing evidence to suggest that there is an effect from paternal age alone as well as a combined effect from advancing paternal and maternal age, relating to increased risks of genetic abnormalities leading to miscarriage or disease in their children.…”

Section: Fertility Of Aging Menmentioning

confidence: 99%

The male biological clock is ticking: a review of the literature

2008

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The term biological clock is usually used by physicians and psychologists to refer to the declining fertility, increasing risk of fetal birth defects and alterations to hormone levels experienced by women as they age. Female fecundity declines slowly after the age of 30 years and more rapidly after 40 and is considered the main limiting factor in treating infertility. However, there are several scientific reports, chapters in books and review articles suggesting that men may also have a biological clock. The aim of our study was to conduct a review of the literature, based on the Medical Literature Analysis and Retrieval System Online (Medline), to evaluate the male biological clock. After adjustments for other factors, the data demonstrate that the likelihood that a fertile couple will take more than 12 months to conceive nearly doubles from 8% when the man is < 25 years old to 15% when he is > 35 years old. Thus, paternal age is a further factor to be taken into account when deciding on the prognosis for infertile couples. Also, increasing male age is associated with a significant decline in fertility (five times longer to achieve pregnancy at the age of 45 years). Patients and their physicians therefore need to understand the effects of the male biological clock on sexual and reproductive health, in that it leads to erectile dysfunction and male infertility, as well as its potential implications for important medical conditions such as diabetes and cardiovascular diseases.

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The Influence of Paternal Age on Down Syndrome

Abstract: Advanced paternal age combined with maternal age significantly influences the incidence of Down syndrome. This effect may represent a paradigm for other genetic abnormalities in children of older fathers.

Cited by 117 publications

References 17 publications

Spermiogenesis and DNA Repair: A Possible Etiology of Human Infertility and Genetic Disorders

Spermiogenesis and DNA Repair: A Possible Etiology of Human Infertility and Genetic Disorders

Paternal age and reproduction

The male biological clock is ticking: a review of the literature

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