Men who wait until they are older to have children are not only risking difficulities conceiving they are increasing the risk of genetic problems

Mutations in the fibroblast growth factor receptor 3 (FGFR 3) gene (above) have been linked to achondroplasia, or dwarfism. Sperm analysis shows that mutations associated with dwarfism gradually increased by about two per cent for every year of age.



June 5, 2006
NR-06-06-01

Study shows that genetic quality
of sperm deteriorates as men age

New research indicates that the genetic quality of sperm worsens as men get older, increasing a man’s risk of being infertile, fathering unsuccessful pregnancies and passing along dwarfism and possibly other genetic diseases to his children.

A study led by scientists at Lawrence Livermore National Laboratory (LLNL) and the University of California, Berkeley, found a steady increase in sperm DNA fragmentation with increasing age of the study participants, along with increases in a gene mutation that causes achondroplasia, or dwarfism. The first changes were observed in men in their early reproductive years.


LANL
Mutations in the fibroblast growth factor receptor 3 (FGFR 3) gene (above) have been linked to achondroplasia, or dwarfism. Sperm analysis shows that mutations associated with dwarfism gradually increased by about two per cent for every year of age.
Earlier research by the same team indicated that male reproductive ability gradually worsens with age, as sperm counts decline and the sperm lose motility and their ability to swim in a straight line. In the current study, the researchers analyzed DNA damage, chromosomal abnormalities and gene mutations in semen samples from the same subjects – 97 healthy, non-smoking LLNL employees and retirees between 22 and 80 years old – and found that sperm motility showed a high correlation with DNA fragmentation, which is associated with increased risk of infertility and a reduced probability of fathering a successful pregnancy.

The study, “Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies (chromosome abnormalities) in sperm,” appears this week in the online edition of the Proceedings of the National Academy of Sciences.

“This study shows that men who wait until they’re older to have children are not only risking difficulties conceiving, they could also be increasing the risk of having children with genetic problems,” said co-lead author Andrew Wyrobek of LLNL.

“We know that women have a biological time clock,” said co-lead author Brenda Eskenazi of UC Berkeley’s School of Public Health, “with an increase in risk of miscarriage and producing children with trisomy (an extra chromosome, such as in Down’s syndrome) as women age, and with a seemingly abrupt end of fertility around perimenopause. Our research suggests that men, too, have a biological time clock – only it is different. Men seem to have a gradual rather than an abrupt change in fertility and in the potential ability to produce viable healthy offspring.”



May 2007 PATERNAL AGE AND AUTISM ARE ASSOCIATED IN A FAMILY-BASED SAMPLE

: Mol Psychiatry. 2007 May;12(5):419-421.Paternal age and autism are associated in a family-based sample.Cantor RM, Yoon JL, Furr J, Lajonchere CM.
[1] 1Department of Human Genetics, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA, USA [2] 2Department of Pediatrics, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA, USA [3] 3AGRE Consortium, Los Angeles, CA, USA.

PMID: 17453057 [PubMed - as supplied by publisher]


The paternal age distribution of the AGRE fathers, whose first child is autistic differs significantly from that of the 'control' sample (P=0.005). A 2 goodness-of-fit test with 2 degrees of freedom was conducted using percents in the 'control' group age categories to calculate the expected values in the AGRE sample. The shift toward higher paternal ages in those with an affected first-born is seen most dramatically in the group of AGRE fathers who are 30–39 years inclusive, which is 54.7% of the distribution compared with the 41.9 % that is expected. We interpret this shifted age distribution to provide support for the recently reported finding by Reichenberg and co-workers that autism risk is associated with advancing paternal age.
Labels: CM Lajonchere, J Furr, JL Yoon, RM Cantor