De novo apparently balanced translocations in man are predominantly paternal in origin and associated with a significant increase in paternal age

: J Med Genet. 2009 Jul 27. [Epub ahead of print]
De novo apparently balanced translocations in man are predominantly paternal in origin and associated with a significant increase in paternal age.Thomas NS, Morris JK, Baptista J, Ng BL, Crolla JA, Jacobs PA.
Salisbury District Hospital, United Kingdom.

BACKGROUND: Congenital chromosome abnormalities are relatively common in our species and among structural abnormalities the most common class is balanced reciprocal translocations. Determining the parental origin of de novo balanced translocations may provide insights into how and when they arise. While there is a general paternal bias in the origin of non-recurrent unbalanced rearrangements, there are few data on parental origin of non-recurrent balanced rearrangements. METHODS: The parental origin of a series of de novo balanced reciprocal translocations was determined using DNA from flow sorted derivative chromosomes and linkage analysis. RESULTS: Of 27 translocations, we found 26 to be of paternal origin and only one of maternal origin. We also found the paternally derived translocations to be associated with a significantly increased paternal age (p<0.008). CONCLUSION: Our results suggest there is a very marked paternal bias in the origin of all non-recurrent reciprocal translocations and that they may arise during one of the numerous mitotic divisions that occur in the spermatogonial germ cells prior to meiosis.

PMID: 19638350 [PubMed - as supplied by publisher]

Data Converges About Older Fathers

Tuesday, July 14, 2009
Data Converges About Older Fathers
A recent post in the New York Times presents some evidence that men who become fathers at a later age have unhealthier children. It is well recognized that men retain their reproductive potential longer, and lose it in a more gradual manner, than do women. Whereas women's fertility declines sharply after age 35 or so, men retain their ability to father children, albeit to a diminished degree, for several decades longer. Recently, some evidence has been presented in the scientific literature that suggests that children conceived with sperm from an older male may have cognitive or psychological challenges compared to those fathered by younger males. A recent study performed by Australian scientists concluded that older dads have children with slightly lower IQs. Others have shown increased rates of schizophrenia, bipolar disorder, and autism in children fathered by older vs. younger men. This evidence suggests that men are susceptible to age-related effects on reproductive ability. This should not surprise anyone. However, the effects of reproductive ageing appear to be expressed differently in males than in females. Dr. Dolores Malaspina, a professor of psychiatry at New York University Medical Center, puts it this way: “It turns out the optimal age for being a mother is the same as the optimal age for being a father.”
posted by Kathleen, Contributing Editor at 1:00 PM

PLoS Genet. 2009 Jul;5(7):e1000558. Epub 2009 Jul 10.
The ups and downs of mutation frequencies during aging can account for the apert syndrome paternal age effect.Yoon SR, Qin J, Glaser RL, Wang Jabs E, Wexler NS, Sokol R, Arnheim N, Calabrese P.
Molecular and Computational Biology Program, University of Southern California, Los Angeles, California, United States of America.

Apert syndrome is almost always caused by a spontaneous mutation of paternal origin in one of two nucleotides in the fibroblast growth factor receptor 2 gene (FGFR2). The incidence of this disease increases with the age of the father (paternal age effect), and this increase is greater than what would be expected based on the greater number of germ-line divisions in older men. We use a highly sensitive PCR assay to measure the frequencies of the two causal mutations in the sperm of over 300 normal donors with a wide range of ages. The mutation frequencies increase with the age of the sperm donors, and this increase is consistent with the increase in the incidence rate. In both the sperm data and the birth data, the increase is non-monotonic. Further, after normalizing for age, the two Apert syndrome mutation frequencies are correlated within individual sperm donors. We consider a mathematical model for germ-line mutation which reproduces many of the attributes of the data. This model, with other evidence, suggests that part of the increase in both the sperm data and the birth data is due to selection for mutated premeiotic cells. It is likely that a number of other genetic diseases have similar features.

Effect of maternal and paternal age on pregnancy and miscarriage rates after intrauterine insemination

Effect of maternal and paternal age on pregnancy and miscarriage rates after intrauterine insemination
Authors: Belloc, Stéphanie1; Cohen-Bacrie, Paul1; Benkhalifa, Moncef2; Cohen-Bacrie, Martine2; De Mouzon, Jacques3; Hazout, André4; Ménézo, Yves1

Source: Reproductive BioMedicine Online, Volume 17, Number 3, September 2008 , pp. 392-397(6)

Publisher: Reproductive Healthcare Ltd


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Abstract:

More than 17,000 intrauterine insemination (lUI) cycles were analysed retrospectively with respect to outcome according to differing aetiologies of infertility. The quantity and motility of spermatozoa in the final preparation used for insemination had a positive effect on the outcome, as classically observed in the past. It was found that advanced maternal age had a negative effect on the pregnancy rate and was associated with increased miscarriage rate. More interestingly, an exactly parallel effect was found for paternal age. The impact of increased age on necrospermia and sperm DNA structure is discussed as a probable direct cause of this paternal effect.
Keywords: IUI; MATERNAL AGE; MISCARRIAGE; PATERNAL AGE

Document Type: Research article

Affiliations: 1: Laboratoire d'Eylau, 55 rue Saint Didier, 75116 Paris, France; Unité AMP Eylau La Muette, 46-48 rue Nicolo 75116, Paris, France; Unité AMP Eylau Cherest, 5 Rue Pierre Cherest 92200 Neuilly sur Seine, France 2: Laboratoire d'Eylau, 55 rue Saint Didier, 75116 Paris, France 3: Unité INSERM 822, 82 rue General Leclerc, 94276 Le Kremlin Bicetre, France 4: Unité AMP Eylau La Muette, 46-48 rue Nicolo 75116, Paris, France

Tick-Tock Goes the Male Biological Clock

Tick-Tock Goes the Male Biological Clock
By: Will Harrison (View Profile)

Scientists Warn That Biological Clock Affects Male Fertility

Wednesday, July 8, 2009

Scientists Warn That Biological Clock Affects Male Fertility
The biological clock ticks for men as well as women, doctors warn today, after research found that male fertility begins to decline when they reach their mid-30s. Doctors said men who wait until their 40s before starting a family face a greater chance of their partner having a miscarriage, because of the poorer quality of their sperm. Researchers examined patient records of more than 12,000 couples treated at a fertility clinic in Paris, and separated out the influence of male and female ages on the couples' chances of having a baby. They found that women whose partners were 35 or older had more miscarriages than those who were with younger men, regardless of their own age. The men's ages also affected pregnancy rates, which were lower in the over-40s. Doctors have long known that a woman's fertility drops sharply in her mid to late 30s, but the effect of age on male fertility is less well understood. Among women, miscarriage rates typically double to 40% between the ages of 20 and 40. The findings are a concern, researchers say, because of the trend for men to delay fatherhood. The latest figures from the Office for National Statistics show the typical age of married fathers rose from 29.1 in 1971 to 34.1 in 2003. The age of men having children outside marriage has remained stable at about 30. And, for the first time, more women in Britain are giving birth in their early 30s than in their late 20s. Yves Ménézo, an embryologist at the Eylau Center for Assisted Reproduction, said older men become less fertile because genetic defects build up in their sperm. In younger men, the damage is minor and can be repaired inside the fertilised egg. But in older men the amount of DNA damage can overwhelm the body's natural repair mechanisms. "We think there's a critical threshold of DNA damage and above that, the damage can no longer be repaired. When that happens, genetic mistakes get through to the embryo and you get an increase in miscarriages," Ménézo said. The findings should cause fertility clinics to reconsider how they treat couples, Ménézo added. Those who fail to conceive after mild forms of fertility treatment, such as intrauterine insemination (IUI), in which sperm is washed and transferred directly into the uterus, should move quickly to more advanced treatments, such as ICSI, where the best quality sperm are picked out and injected directly into the woman's egg. The study looked at pregnancies and miscarriages recorded for couples having IUI treatment at the clinic between 2002 and 2006. It found the risk of miscarriage was on average 16.7% when men were aged 30-34. That rate rose to 19.5% when men were 35-39 and 33% in men aged 40 or over. Stéphanie Belloc, lead author of the study, which is due to be published in the journal RBM Online, said: "Until now, gynaecologists only focus on maternal age, and the message was to get pregnant before the age of 35 or 38 because afterwards it would be difficult. But now the gynaecologists must also focus on paternal age and give this information to the couple." She is to discuss her findings at the annual European Society of Human Reproduction and Embryology meeting in Barcelona today. Jacques de Mouzon, a co-author at the French National Institute for Medical Research, said: "People say men are fertile into old age, 90 even. That may be true sometimes, but the product is different and there are more semen abnormalities as age advances. There is a decrease [in male fertility] and an increase in the spontaneous abortion rate after the age of 40 and especially after 45. It is necessary for men to try to have children before the ages of 40 to 45." Previous research has pointed to a slight increase in birth defects in babies born to older men. A 2005 study of 70,000 couples by epidemiologist Jorn Olsen at the University of California, Los Angeles, found a fourfold rise in Down's syndrome among babies born to men aged 50 and older. They were also more likely to have limb deformities. The chances of having a baby with Down's syndrome increase rapidly with a woman's age. About one in 1,000 babies born to mothers under 30 have it, a figure that rises to one in 400 by the age of 35 and one in 105 by the age of 40. "There is growing evidence from a number of studies to show that men are not totally immune from reproductive aging," said Allan Pacey, an expert in male fertility at Sheffield University. "Previous studies of couples trying to conceive naturally or undergoing IVF have shown that men over the age of about 40 are less fertile than younger men."
Posted by TEEBOB at 6:10 PM