Is ’60s sperm still any good?

20. October 2011

Even before menopause becomes the issue, the risk of having children with disabilities increases for women beyond forty. Men can still become fathers even in old age. But what kind of risks do they pass off to their offspring?

“Kaiser Franz” was almost sixty when the fifth child of the football star was born, the former Finance Minister Theo Waigel 56 when former Alpine skier Irene Epple gave him another son. Nicolas Sarkozy (56) and Carla Bruni (44) are expecting the arrival of their first child together in a few weeks. Hardly anyone doubts that these people, who are really more in the “Grandpa age” range, have been or will be caring fathers.

It’s not only celebrities nearing retirement, or even later still, who are allowing themselves one more child. In the industrialised Western nations, parent-age in recent decades has risen sharply. In the mid-seventies, a mother was, at the birth of the child, on average just under 27 years old, the father 29. Today, both parents are about three years older. However: every hundredth child among children born to mothers over 40 suffers from trisomy 21. How high the risk of genetic defect is for the offspring of old fathers hardly anyone knows.

With each additional year, lower sperm speed

While Down syndrome is due mainly to the mother, there are among the offspring of senior males a range of diseases and defects which turn up more frequently along with an increasing age in reproductive fatherhood. These include growth disorders such as achondroplasia and Apert syndrome, but also mental ailments such as autism, schizophrenia, epilepsy or bipolar disorder. On the whole, sperm quality decreases along with fertility. And that’s already at just thirty years of age. Brenda Eskenazi from the American Berkeley University concludes a value of 0.7 percent less sperm mobility per year. Study results here are not always in agreement. For instance, a Belgian group found, at least in a comparison of sperm from men in their early thirties to that belonging to those in their forties and older, no differences in morphology, concentration as well as in motility.

A closer look at alerations in the DNA reveals that it is mainly spontaneous mutations which take a toll on the genetic material of the zygote. During the development of sperm, nature however provides plenty of opportunity for interference in the genomic composition of the gametes. While oocytes divide 24 times before they leave the ovary, the male germ cells divide every sixteen days after puberty. By the age of 40 therefore they have almost 700 mitotic divisions in their past.

Hotspot for seniors’ sperm: FGFR2

Sperm researchers dedicate particular attention to the fibroblast growth-factor receptor (FGFR2 and FGFR3) gene, which is responsible for malformations of the skull. With Crouzon syndrome (caused by premature skull binding adhesions), the frequent de novo mutations establish themselves almost exclusively along the paternal genetic component. Researchers have found about 40 different DNA aberrations in the FGFR2 gene. Apert syndrome, incidence of which rises with increasing father-age, is also traced back to this gene. Still little studied, but probably also involved, are epigenetic defects: that is, disruptions to the expression of important genes in the genome.

Increased risk: autism, schizophrenia, bipolar disorder.

Some insightful studies on the other hand make a connection between aged sperm and children with autism. Recruitment data gained by the Israeli army was used by epidemiologists in order to search out the father-age of a total number of 110 autistic children. According to their analyses, there was a sixfold increase in the risk of having a child with a handicap when men over forty had decided to start a family compared to those in their twenties. One American study arrived at a twenty-two percent additional risk for each decade of life of the father. Even greater – 38 percent – was, however, the calculable risk contribution for the mother. 

Similar risks for children of fathers at an advanced age are seen by a Swedish study on Bipolar Disorder. In regard to schizophrenia, a metastudy of the numbers of individual studies calculated in summary a two-to four-fold rise as compared to men in their peak reproductive years. Animal sudies with mice have since confirmed that mutations “picked“genes associated with autism and schiziphrenia .

More intelligent children with a young father and older mother

John McGrawth from Queensland, Australia, is generally interested in the intelligence of children who were fathered by men of advanced age. In 2009 he published the surprising result of his epidemiological studies in the journal PLoS Medicine. He evaluated the data of some 33,000 American children who were tested at the ages of eight months, four years and seven years for their cognitive abilities such as concentration, learning and understanding. Whereas an increasing age at fatherhood is reflected negatively in the capacities of the offspring of those fathers, the intellectual abilities in children of mothers of an advanced age tend to be higher. There is for this phenomenon as yet still no explanation.

Magnetic resonance imaging also shows changes in brain anatomy: Children of older fathers have, according to the analysis of cortical gray matter, less cortex surface, for older mothers it corresponds to lower volume. In white matter, the researchers observed no difference.

Senior Pa costs two years of life

With data from approximately 103,000 couples, a Danish group have calculated the relationship between child mortality and fatherhood age for children at all ages up to the point of adulthood. Seniors provide their offspring, consequently, with approximately one and a half times greater risk of premature death. One team from Russia published study outcomes in Science in 1997, according to which daughters lost about two years of life where their fathers were older than 45 when the daughters were born. 

There is little information so far, as to what extent the level of social protection of a settled father has an impact on the life and health of the offspring since the problems brought about by aged sperms are rather rare. Gideon Sartorius and Eberhard Nieschlag from Munster and Basel see, in any case, in their publication no reason for “invasive procedures” during pregnancy – a situation which is in contrast to mothers in their forties.

However, there are also, beyond the medical, other aspects which are involved in the decision for or against having a child: for example, the declining energy available for parenting and fewer opportunities for child care by grandparents.
In the end, a man can also do something in order to keep his treasured assets as fit as possible: balanced nutrition. Vitamin B12 and folic acid in particular seem to play an important role in the fight against mutation by oxidating radicals. Ultimately it’s not only that gametes benefit from a man’s health, but it also helps him in obtaining many years to share time with his offspring.

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