Paternal age and sperm DNA decay: discrepancy between chromomycin and aniline blue staining

Reprod Biomed Online. 2009 Aug;19(2):264-9.
Paternal age and sperm DNA decay: discrepancy between chromomycin and aniline blue staining.Belloc S, Benkhalifa M, Junca AM, Dumont M, Bacrie PC, Ménézo Y.
UNILABS, Centre d'AMP Eylau, Clinique Pierre Cherest et Clinique de la Muette, 55 Rue Saint Didier, 75116 Paris, France.

The effect of paternal age on sperm DNA fragmentation and decondensation was determined in a retrospective study involving 1769 patients. TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end labelling (TUNEL) assay was used to assess fragmentation, and DNA decondensation was measured with either chromomycin or aniline blue staining. The impact of atypical forms was also analysed. DNA fragmentation increases with age, but is independent of the percentage of atypical forms. Both staining techniques revealed a negative correlation between the quality of sperm packaging and the percentage of atypical forms. Decondensation increases with increasing age and fragmentation when measured with chromomycin; however, an inverse relationship is observed when testing is performed using aniline blue. These observations are discussed in relation to the specificity of the dyes, the deposition of protamines and the impact of age and reactive oxygen species on protamine cross-linking.

PMID: 19712565 [PubMed - in process]

Best before (34)

Best before
Posted By MARILYN LINTON, SUN MEDIA
Posted 12 hours ago
Do men have a best-before date when it comes to fathering kids? Ridiculous, most of us would answer. Just look at these celebrity old guys who became dads in their 50's, 60's, and beyond: Charlie Chaplin at 73; former Prime Minister Pierre Trudeau at 72, Pablo Picasso at 68; Larry King at 65; Warren Beatty at 63; and Dave Letterman at 56.
"Women are born with a fixed number of oocytes," says Dr. Bernard Robaire, describing the female germ cells crucial to reproduction. The McGill University researcher who is funded by the Canadian Institutes of Health Research or CIHR, says that men have no such limitation. Unlike women who, after the age of 35 find it more difficult to get pregnant, men produce 1,000 sperm a heartbeat - about 100 million sperm each day.
Theoretically speaking, then, men can go forth and multiply forever - or as long as their hearts beat. "The argument has always been that because men keep producing sperm that are fresh all the time it makes no difference whether you have sperm from an 85 year old man or a 35 year old man," says Robaire.
However, there's a growing body of research that suggests there may be limits to men's fertility, too. Recent studies have shown that men over the age of 40 have a lower chance of producing children than their younger counterparts. And they have an elevated risk of having children with autism, bipolar disease and schizophrenia.
In addition to concerns about mental illness, some studies have also shown that children born to older fathers score lower on intelligence tests. One study found that the incidence of down syndrome was related to sperm approximately 50% of the time.
"What we found was that if you put old males with young females the development of the embryos was different," says Robaire, explaining his work with lab rats. "We found a change in the weight of the embryos, but what was most striking was an increase in the post-natal death right after birth. Development was not normal.
"It seems that, as men age, the quality of their sperm changes," he explains. "The sperm's swimming ability changes, and the quality of its DNA decreases." So even though men continue to produce fresh sperm, the quality suffers because the sperm, which come from aging stem cells in the testes, accumulate oxidative damage over time.
"Fertility doesn't decline - only the quality of the sperm," he stresses. So is there a biological clock for men? "Yes, because a biological clock doesn't just refer to the number of sperm produced but also their quality." Robaire adds that there are many older men who produce children who are normal in every way. Nonetheless, studies show that the best age for perfect sperm is under 40.
With older men increasingly fathering children, the issue of sperm quality needs to be heard, says Robaire. "All our worries are about women having kids over the age of 35. But a man's sperm quality decreases with age and so therefore do the chances of his children being normal."

What will reduce the amount of autism and schizophrenia in the population?

What will reduce the amount of autism and schizophrenia in the population?
August 22, 2009 | By admin In Autism |
Alex

90 % of autism and and 85 -90 % of schizophrenia is de novo, sporadic, non-familial
Is paternal age and risk of autism plausable biologically?

RESULTS: There was a significant monotonic association between advancing paternal age and risk of ASD. Offspring of men 40 years or older were 5.75 times (95% confidence interval, 2.65-12.46; P<.001) more likely to have ASD compared with offspring of men younger than 30 years, after controlling for year of birth, socioeconomic status, and maternal age. Advancing maternal age showed no association with ASD after adjusting for paternal age. Sensitivity analyses indicated that these findings were not the result of bias due to missing data on maternal age. CONCLUSIONS: Advanced paternal age was associated with increased risk of ASD. Possible biological mechanisms include de novo mutations associated with advancing age or alterations in genetic imprinting.

Here's the Truth About The Paternal Age Effect

A Man's Shelf Life
Fertility wanes, risks increase with age.
Mark Teich Premium Health News Service
August 21, 2009

Women have long understood that general fitness and age are both critical to conceiving a healthy child. But their partners often feel absolved of such concerns; men tend to think they can drink, carouse, smoke like coal trains, and conceive whenever they want, with no impact on fertility or their future offspring. Would that it were so.

but old sperm may be contributing to increases in autism, schizophrenia and Alzheimer's.

The Pros and Cons of Being a Grandpa-Daddy RT @momlogic Share:
The Pros and Cons of Being a Grandpa-Daddy

Wednesday, August 19, 2009
filed under: pregnancy & baby logic
There are physical and emotional consequences to having kids at such a late stage of life.

Michelle Golland, Psy.D.: With the wonderful news that Celine Dion, 41, is pregnant with her second child with her husband Rene, who is 67 years old, I wanted to share the pros and cons of being a Grandpa-Daddy. I choose that title because most of the men who are conceiving children beyond their 60s are most likely on their second wife and have older kids from their first marriage who have kids of their own as well.

There are physical and emotional consequences to having children at such a late stage of life. Because Celine Dion is a relatively young woman, she will be around to raise the children if anything were to happen to Rene. Let's be honest -- another positive is the fact that these children will not be concerned for their financial future in any way, which is usually a concern when becoming a parent at the age of 67. So when this child is 18, Rene will be 85.

Cons
Old sperm: Researchers are finding that it is not just our eggs that get old and cause all the problems, but old sperm may be contributing to increases in autism, schizophrenia and Alzheimer's.


Death/lost role model: Your children won't get to see you in your middle ages and you certainly won't see them in their 30's and having children. Your kids will most likely bury you.


Social stigma: You will be mistaken for the grandpa. Your kids' friends and their parents will assume that you are grandpa due to your age -- plain and simple. This will be embarrassing for your children -- and it will be a topic they will continue to explain their whole life.

Pros
Older dads are more involved in parenting, and are typically more nurturing, affectionate and gentle. Studies have shown that this may be caused by the drop in testosterone as men age.


Older dads are three times more likely to show equality in parenting. They change diapers, feed and bathe their children more often than younger dads.


Kids of older dads usually have higher self-esteem, more confidence, greater sense of security, better ability to handle stress and are more empathic.

We found that paternal age at conception is a robust risk factor for schizophrenia, explaining perhaps a quarter of all cases.

Novartis Found Symp. 2008;289:196-203; discussion 203-7, 238-40.Links
Growth and schizophrenia: aetiology, epidemiology and epigenetics.Malaspina D, Perrin M, Kleinhaus KR, Opler M, Harlap S.
Department of Psychiatry, New York University School ofMedicine, New York, NY 10016, USA.

There is a strong genetic component for schizophrenia risk, but it is unclear how the illness is maintained in the population given the significantly reduced fertility of those with the disorder. One possibility is that new mutations occur in schizophrenia vulnerability genes. If so, then those with schizophrenia may have older fathers, since advancing paternal age is the major source of new mutations in humans. We found that paternal age at conception is a robust risk factor for schizophrenia, explaining perhaps a quarter of all cases. The predisposing genetic events appear to occur stochastically in proportion to advancing paternal age, and the possible mechanisms include de novo point mutations or defective epigenetic regulation of paternal genes. The risk might also be related to paternal toxic exposures, nutritional deficiencies, suboptimal DNA repair enzymes or other factors that influence the fidelity of genetic information in the constantly replicating male germ line. We propose that de novo genetic alterations in the paternal germline cause an independent and common variant of schizophrenia and that abnormal methylation of paternally imprinted genes could be the mechanism. These findings suggest exciting new directions for research into the aetiology of schizophrenia.

Paternal age as a risk factor for schizophrenia: How important is it?

Schizophr Res. 2009 Aug 13. [Epub ahead of print]
Paternal age as a risk factor for schizophrenia: How important is it?Torrey EF, Buka S, Cannon TD, Goldstein JM, Seidman LJ, Liu T, Hadley T, Rosso IM, Bearden C, Yolken RH.
The Stanley Medical Research Institute, 8401 Connecticut Ave., Suite 200, Chevy Chase, MD 20815, USA.

Advanced paternal age has been widely cited as a risk factor for schizophrenia among offspring and even claimed to account for one-quarter of all cases. We carried out a new study on 25,025 offspring from the Collaborative Perinatal Project (CPP), including 168 diagnosed with psychosis and 88 with narrowly defined schizophrenia. We also conducted a meta-analysis of this and nine other studies for which comparable age-cohort data were available. The mean paternal age for the CPP cases was slightly, but not significantly, higher than the matched controls (p=0.28). Meta-analyses including these new results were conducted to determine the relative risk associated with alternative definitions of advanced paternal age (35, 45 or 55years and older). These yielded pooled odds ratios and 95% confidence intervals of 1.28 (1.10, 1.48), 1.38 (0.95, 2.01) and 2.22 (1.46, 3.37), respectively. Thus, increased paternal age appears to be a risk factor for schizophrenia primarily among offspring of fathers ages 55 and over. In these 10 studies, such fathers accounted for only 0.6% of all births. Compared with other known risk factors for schizophrenia, advanced paternal age appears to be intermediate in magnitude. Advanced paternal age is also known to be a risk factor for some chromosomal and neoplastic diseases in the offspring where the cause is thought to be chromosomal aberrations and mutations of the aging germline. Similar mechanisms may account for the relationship between advanced paternal age and schizophrenia risk.

Older Paternal Age Seen as Factor in Some Birth Defects - New York Times June 6, 2006

As men get older, their sperm deteriorates, a new study has found, and it is likely that the damaged sperm of older men is a significant factor in certain specific birth defects and in increasing the risk of abnormal pregnancies.Birth rates since 1980 have increased by 40 percent in men 35 to 40 and decreased by 20 percent in men under 30, according to background information about the findings, published yesterday in The Proceedings of the National Academy of Sciences. The rising age of fathers has been associated with reproductive problems including spontaneous abortion and with genetic ...