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HUMAN
REPRODUCTION
Sperm aneuploidy rates in younger and older men
Luetjens CM, Rolf C, Gassner P, Werny JE, Nieschlag E
From the Institute of Reproductive Medicine, Westphalian Wilhelms-University,
Muenster, Germany
Hum Reprod. 2002; 17:1826-32
- Background:
In order to assess the possible risk of chromosomal abnormalities in
offspring from older fathers, we investigated the effects of age on
the frequency of chromosomal aneuploidy rates of human sperm.
- Methods
and Results:
Semen samples were collected from 15 men aged <30 years (24.8 +/-
2.4 years) and from eight men aged >60 years (65.3 +/- 3.9 years)
from the general population. No significant differences in ejaculate
volume, sperm concentration and sperm morphology were found, whereas
sperm motility was significantly lower in older men (P=0.002). For the
hormone values, only FSH was significantly elevated in the older men
(P=0.004). Multicolor fluorescence in-situ hybridization was used to
determine the aneuploidy frequencies of two autosomes (9 and 18); and
of both sex chromosomes using directly labeled satellite DNA probes
on decondensed sperm nuclei. A minimum of 8000 sperm per donor and >330
000 sperm in total were evaluated. The disomy rates per analyzed chromosomes
were 0.1-2.3% in younger men and 0.1-1.8% in older men. The aneuploidy
rate determined for both sex chromosomes and for the autosomes 9 and
18 were not significantly different between the age groups.
- Conclusions:
The results suggest that men of advanced age still wanting to become
fathers do not have a significantly higher risk of procreating offspring
with chromosomal abnormalities compared with younger men.
- Editorial
Comment
Numeric chromosomal anomalies (aneuploidy) result from nondisjunction
during a meiotic division. It is well known that these anomalies increase
with maternal age, which may be explained by oocyte aging. For example,
the risk for Down syndrome for women in their 30s is 1/952, increasing
to 1/378 at 35 years old, and 1/106 at their 40s (1). On the other hand,
the association between paternal age and chromosomal abnormalities is
not well established. Although others corroborate the findings of the
present study, few chromosomes were analyzed, and very few patients
were studied
Not only aneuploidy may be sperm-derived but also structural anomalies
and single gene defects (mutations). Contrary to the findings on paternal
age and aneuploidy, a positive relationship exists between paternal
age and the frequency of structural anomalies in sperm (2). However,
there is no evidence that this age-related association leads to an increased
frequency of offspring with structural anomalies.
Although the incidence of chromosomal disorders in children does not
appear to exhibit an paternal age-related increase, there is no question
of the association between single gene defects and advanced paternal
age. Single gene defects are the result of errors in the DNA replication
process. They can lead to an increase likelihood of autosomal dominant
diseases, such as hemophilia A, Marfan syndrome, polycystic kidney disease,
neurofibromatosis, achondroplasia, etc. It is estimated that the risk
for a father over 40 years old to have a child with an autosomal dominant
mutation equals the risk of Down syndrome for a child whose mother is
35-40 years old (3). Other anatomic birth defects, including ventricular
and atrial septal defects, and situs inversus, may be also related to
the increase in paternal age (4).
References
1. Maternal Fetal Medicine: Practice and Principles. Creasy M, Resnick
M (eds.), Philadelphia, WB Saunders, 1994, p. 71.
2. Martin RH, Rademaker AW: The effect of age on the frequency of sperm
chromosomal abnormalities in normal men. Am J Hum Genet. 1987; 41:484.
3. Friedman JM: Genetic disease in the offspring of older father. Obstet
Gynecol. 1981; 57:745.
4. Lian Z-H, Zack MM, Erickson JD: Paternal age and occurrence of birth
defects. Am J Hum Genet. 1986; 39:648.
Dr. Sandro C. Esteves
Androfert
Campinas, SP, Brazil
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