Wednesday, May 02, 2007

ADVANCING PATERNAL AGE IS ASSOCIATED WITH A GRADUAL AND SIGNIFICANT INCREASE IN THE RISK OF FATHERING CHILDREN WITH VARIOUS CHROMOSOMAL DEFECTS

1: Fertil Steril. 2007 Apr 10; [Epub ahead of print] Links
Frequency of human sperm carrying structural aberrations of chromosome 1 increases with advancing age.Sloter ED, Marchetti F, Eskenazi B, Weldon RH, Nath J, Cabreros D, Wyrobek AJ.
Biosciences Directorate, Lawrence Livermore National Laboratory, Livermore, California; Genetics and Developmental Biology Program, West Virginia University, Morgantown, West Virginia; Department of Epidemiology, School of Public Health, University of California, Berkeley, California.

OBJECTIVE: To investigate the association between male age and the frequency of sperm with de novo structural chromosomal abnormalities. DESIGN: Semen specimens collected from two groups of 10 healthy, nonsmoking men, aged 22-28 and 65-80 years, were analyzed with the use of a multicolor fluorescence in situ hybridization assay for detecting breaks, segmental duplications and deletions, and aneuploidy and diploidy involving chromosome 1. SETTING: Healthy volunteer workers and retirees from a government research environment. MAIN OUTCOME MEASURE: Sperm carrying numerical and structural chromosomal abnormalities. RESULT(S): We detected significant increases in the frequency of sperm carrying breaks and segmental duplications and deletions of chromosome 1 among older men compared with younger men. Older men carried twice the frequency of sperm with segmental duplications and deletions of chromosome 1. The frequency of sperm carrying breaks within the 1q12 fragile-site region nearly doubled in older men. In contrast to female gametes, there was no effect of age on the frequency of sperm with numerical chromosomal abnormalities. CONCLUSION: Our findings suggest that advancing male age is associated with a gradual and significant increase in the risk of fathering children with various chromosomal defects such as segmental aneusomy syndromes.

PMID: 17433321 [PubMed - as supplied by publisher]




Overall, our findings suggest that the increasing trend of fathering children at older ages predicts a greater incidence of abnormal reproductive outcomes and genetic diseases of paternal origin resulting from chromosomal breaks, duplications, and deletions, assuming that sperm with these abnormalities are as likely to fertilize as normal sperm. A broad spectrum of abnormal reproductive outcomes was associated with the types of chromosomal defects that we detected in sperm, such as spontaneous abortions, neonatal death, birth defects, developmental delay, and mental retardation. Specifically, our data predict that advancing paternal age may be associated with an increased risk for offspring carrying the 1p36 deletion syndrome. Aging men are also predicted to be at increased risk for transmitting the 1p36 duplication product to offspring, although the health consequences associated with duplications are less understood than those of deletions. Our observed association of age with the frequency of sperm with a 1q12 breakage may have significant clinical implications, given the general concurrence between genomic fragile sites and de novo breakpoint locations of chromosomal rearrangements in spontaneous abortions and newborns (83).

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2 Comments:

At 10:47 AM , Anonymous Anonymous said...

Sorry this comment is non-specific to the entry, but I love your blog. I would love to follow all the updates you can get your hands on, and I hope the readership will be expanded so that more people are aware of fertility issues that may affect their future and their children's quality of life.

Some people have proposed that this information be included in basic sexual and health education in school. I agree, and I'm wondering what we can do to push issues like this to the fore, and if you intend to blog your own opinion about influencing the public sphere.

My concerns are not unfounded; my home state, NJ, requires all people to be accomodated in school, no matter what the cost of their disability. I love this about my state, but nowadays, I love it more in theory than in practice. As a particularly well-educated, career-oriented state, more couples are likely to put off family life until they have pursued the upper eschelons of academia and dominated their respective fields. It's for this reason I doubt that the exceptionally high rate of autism in NJ is merely due to better access to diagnosticians than average.

Of course, I can't help but wonder what could have been done for me and other overlooked gifted individuals if the amount being spent on intervention therapies were diverted to individualized learning programs for bright children instead.

Even if educational spending wouldn't be redirected due to a shift in priorities, the tax burden of the epidemic must be addressed immediately; as is already obvious to you, these paternal mutations are not only an issue affecting individually diagnosed children and their families. Our entire democracy will probably be forced to change dramatically to accommodate or prevent the outcome of collective scientific ignorance. What's that old saying? An ounce of prevention...

-K.A.

 
At 11:35 AM , Anonymous Anonymous said...

It is great to hear from you and what you said is so true. This is an issue as important as global warming to our country and I fear the studies done on paternal age and cognitive disorders are the tip of the iceberg as far as advancing paternal age's impact on depression, and intellectual disability. Men must be encouraged to cryobank their sperm in their 20s if they might father babies after 31 or 32. Paternal age is implicated in breast and prostate cancer, and Alzheimer’s, diabetes type 1, etc. If you have read the blog you know of the scope of what has been researched. Help by letting your friends know. If anyone teaching in a private school maybe they could add this information to the curriculum. It should be in every curriculum. My opponents are the pharmas, the psychiatrists who are psycho pharmacologists, the CDC, the NIH. They won’t allow this information in the curriculum and they have made sure people are taught that men do not have a biological clock. It has to be passed person to person at this point. http://press.psprings.co.uk/jech/october/851_ch45179.pdf

 

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