The Biological Clock. Are Men and Women Really That Different?

>> Wednesday, September 19, 2012

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When it comes to fertility and the prospect of having healthy babies, it has always been assumed that men have no biological clock, and that unlike women, they can have it all, at any age.   Perhaps this is because women go through menopause and stop having periods/ovulating at around age 51-52.  We lose our ability to have children past this age.  Of course, the advancement of infertility methods and donor eggs in the past few years has really changed all that and made carrying children at an older age possible.

The amazing truth is, and has always been, that if an embryo is unhealthy with defects incompatible with life, it is miscarried early.   We see this happen more often as women get older because we are born with all the eggs we will ever have.  During a lifetime the genetic material in each individual egg can become damaged through the normal course of life, not from any extra-ordinary illnesses or problems.  At fertilization, the chromosomes (23 from the sperm and 23 from the egg) combine to create a normal human life.  When an egg that may have damaged chromosomes combines with the sperm, the egg may contribute the wrong number of chromosomes.  

Human babies should have 23 pairs of chromosomes, one each from mom and dad.  A child with Down Syndrome will have 3 copies of chromosome 21 (trisomy 21).   Two come from mom and one from dad, and the other egg where the extra 21 was taken from will have zero chromosome 21.  So either a baby is born with mental or physical defects or miscarried.  Men make new sperm about every 72 days so this type of abnormality is unlikely in sperm.  Down Syndrome is the most common birth defect seen in older women having babies.  The rest of the birth defects are now thought to come from the father or are seen more often in younger women. 

Until now, the dominant view has been, “blame it on the mother,” but research has shown a dose-response relationship - meaning the older the father and the mother, the higher the risk.  When mom is over 35, combined with an older father, this adds to the risk of having a baby with Down Syndrome.  The father's age seems to have no effect if the mother is younger;  younger women may have compensated for any problems of the older male.  Other findings suggest implications for older fathers and find a correlation between having an older father and lower scores on nonverbal, or performance, IQ tests.

These newer studies are alarming because they found higher rates of more common conditions,  including autism, ADD, and schizophrenia, in offspring born to men in their middle and late 40s.

Analyses of sperm samples from healthy men have found changes as men age, including increased fragmentation of DNA.  Geneticists have been aware for decades that the risk of certain rare birth defects increases with the father's age.  One of the most studied of these conditions is a form of dwarfism called achondroplasia, but the list also includes neurofibromatosis (Elephant Man), the connective tissues disorder Marfan syndrome, skull and facial abnormalities like Apert syndrome, and many other diseases and abnormalities.

What happens is that, as men age, the number of new mutations in their sperm (and the likelihood that some of these errors will be passed to offspring) increases.  As a result, the worldwide trend of men starting families later in life may be part of the reason why conditions such as autism and schizophrenia are on the rise.  Research has found that, for every year a man ages, 2 more new gene mutations appear in his offspring. They calculated that the number doubles every 16.5 years from puberty onward, meaning that 36-year-old men pass on twice as many mutations to their children as do 20-year-olds.

As women age, they are at greater risk of having a child with Down Syndrome or other rare chromosomal abnormalities, yet men transmit about 4 times more new gene mutations to children. Experts think this disparity may have something to do with the fact that men continually make new sperm with the help of dividing precursor cells, which acquire new mutations with every division.

Some studies suggest that the risk of sporadic single-gene mutations may be four to five times higher for fathers who are 45 and older, compared with fathers in their 20s.  A recent study on autism and ADD attracted attention because of its striking findings related to this - because so much attention was focused on immunizations causing a rise is autism and ADD.  Now with the current findings on all research across the ethnic groups and socio-economic classes, it has found that children of men who became a father at 40 or older were 5.75 times as likely to have an autism disorder or ADD as those whose fathers were younger than 30.

Likewise, a study on schizophrenia found that the risk of illness was doubled among children of fathers in their late 40s when compared with children of fathers under 25, and the risk increased almost threefold in children born to fathers 50 and older.  The most recent studies calculate the risk of schizophrenia at 1 in 141 among children of fathers under 25 years, 1 in 99 for fathers 30 to 35, and 1 in 47 for fathers 50 and older. The study found no association between older fathers and any other psychiatric conditions.

So, that's a lot for us girls to think about as we've always looked at the men as having no biological clock and wondered why we go through menopause and have to worry about having families at an early age.  Now, with this new information, it looks like our male counterparts need to be thinking about marriage and families earlier as well, in order to be sure they are passing on healthy genes.  

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