Biological clocks for men

The equal distribution of chromosomes during oogenesis is particularly error-prone for women. During meiosis, the process by which gametes form, the chromosomes undergo two divisions that reduce the numbers of each chromosome from the diploid number (2) to the haploid number (1n) found in germ cells. Too many chromosomes in an egg leads to trisomy and too few leads to monosomy. When this segregation goes awry, nondisjunction of chromosomes can lead to eggs with either too many or too few chromosomes. When fertilized by sperm the resulting zygote the extra copy of the chromosome that had failed to properly disjoin plus the normal 2n number of the rest of the chromosomes to give (2n+1). Those with trisomy 21 will have Down syndrome. Trisomy 13 leads to Patau syndrome and chromosome 18 to Edwards syndrome. Mental retardation and other clinically notable features are characteristic of those with Down Syndrome. These individuals live to adulthood and, depending on the severity of the syndrome, can live semi-independently. Those born with trisomy 13 and 18 usually live only a few hours or days after birth. Because of the risk of having a child with a trisomy increases as a woman ages, she is acutely aware of her life's arc with respect to child bearing. This risk increases dramatically from age 35 and onward so that the incidence of trisomy is a very real concern. But what about men? A recent article in the Sunday magazine of the New York times (4/5/09) reports that children born to fathers older than 40 years old have an increased risk of conceiving children that are likely to score lower than normal on tests of concentration, memory, reasoning and reading skills, at least through age 7. In addition there is a nearly 9-fold chance of a child having symptoms that fall into the range of autism spectrum disorder in men who become fathers at age 50 compared to 15-29 year old fathers.

So, whats up with nondisjunction and does this relate to fathers? Nondisjunction in females may be due to the inability of homologous chromosomes (the chromosomes a woman inherited by her mother and father, respectively) to hold together for decades. This is because the first stages of female meiosis occur in the fetus. In the first meiotic division, homologous chromosomes pair up and segregate from one another. The problem is that these chromosomes must remained paired until the time of ovulation. So if a women chooses to have a child in her 40's, those chromosomes have persisted in the paired state for 4-decades! It is amazing to think those chromosomes held together for so long, all 46 of them. In fact, many don't. While the incidence of trisomy among live births increases with age, so does the incidence of nonviable trisomies. Up to 30% of conceptions are thought to have at least one trisomy (or monosomy) and these are typically aborted spontaneously even before a woman even knows she is pregnant. Miscarriage is also often due to aneupolidy (having the wrong number of chromosomes) as well.

Men on the other hand have a stem-cell population from which sperm are formed continuously after puberty. Since every sperm comes from a brand new meiosis, the incidence of trisomy is less common. In addition, male meiosis appears to be subject to more robust mechanisms of surveillance to detect errors in chromosome segregation and arrest sperm development. The stem-cell population is not immune to other types of genetic errors including mutations or changes in chromosome modification patterns that might arise in the cell divisions leading up to spermatogenesis. Do these mutations lead to the higher incidence of mental disorders? The evidence is correlative at best. But perhaps men will begin to view the biological clock through the same lens as women; a view that weighs heavily on a woman planning on both a family and a career involving many years of post-graduate education.