Women have long understood that general fitness and age are both critical to conceiving a healthy child. But their partners often feel absolved of such concerns; men tend to think they can drink, carouse, smoke like coal trains, and conceive whenever they want, with no impact on fertility or their future offspring. Would that it were so.
"Everybody was familiar with the concept of women's biological clock, but when we introduced 'male' to the equation, the reaction was 'What are you talking about? Men can have children at any age,'" recalls urologist Harry Fisch, director of the Male Reproductive Center at Columbia Presbyterian Hospital in New York City and author of The Male Biological Clock. "It became a social issue. Men do not like to be told they have a problem."
Nonetheless, a virtual tidal wave of research has made it irrefutable: Not only does male fertility decrease decade by decade, especially after age 35, but aging sperm can be a significant and sometimes the only cause of severe health and developmental problems in offspring, including autism, schizophrenia, and cancer. The older the father, the higher the risk. But what's truly noteworthy is not that infertility increases with age—to some degree, we've known that all along—but rather that older men who can still conceive may have such damaged sperm that they put their offspring at risk for many types of disorders and disabilities.
"Men thought they were getting off scot free, and they weren't. The birth defects caused by male aging are significant conditions that can cause a burden to families and society," says Ethylin Wang Jabs, professor of pediatric genetics at Johns Hopkins University and leader of a study showing the link between aging paternity and certain facial deformities in offspring. "We now know that men and women alike could be increasing the risk of infertility or birth defects by waiting too long to have children." In other words, by looking for perfection in your life before you conceive, there's a very real chance you'll have less perfect kids."
Studies worldwide have found that with each passing decade of their lives and with each insult they inflict on their bodies, men's fertility decreases, while genetic risk to offspring slowly mounts. The range of findings is staggering: Several studies have shown that the older the man, the more fragmented the DNA in his ejaculated sperm, resulting in greater risk for infertility, miscarriage or birth defects. Investigations out of Israel, Europe, and the United States have shown that non-verbal (performance) intelligence may decline exclusively due to greater paternal age; that up to a third of all cases of schizophrenia are linked to increasing paternal age; and that men 40 and older are nearly six times more likely to have offspring with autism than men under age 30. Other research shows that the risk of breast and prostate cancer in offspring increases with paternal age.
Fisch has found that when both parents are over 35, paternal aging may be responsible for as many as half of all cases of Down syndrome, formerly thought to be inherited from the mother. And studies show that half a dozen or more rare but serious birth defects appear to be inherited exclusively from the father, including Apert syndrome, Crouzon syndrome, and Pfeiffer syndrome (all characterized by facial abnormalities and the premature fusion of skull bones) as well as achondroplasia (the most common form of dwarfism).
Male versus Female Mutations
Scientists have long known that advanced paternal age (like increased maternal age) played some role in fertility problems and birth defects. Yet because the reports mainly involved children who died before birth or who had extremely rare disorders, no one really rang the alarm. Now, with studies linking the father's age to relatively frequent, serious conditions like autism, schizophrenia, and Down syndrome, the landscape is shifting.
Women have unfairly borne the brunt of the blame for birth defects. When the conditions were familial, passed on through chromosomal lineage, women were somehow widely believed culpable, even though such defects can be traced to either partner. "But what we're finding now is that in humans as well as in other mammals, when there's a new genetic change—called 'de novo or sporadic point mutation'—it almost always happens in the male parent," says Dolores Malaspina, chair of psychiatry at New York University Medical Center. And these de novo mutations increase in frequency with the age of the male parent.
These mutations could reflect the differences in male and female reproduction, notes Jabs. By the time females reach their teen years, their eggs have already been formed—just one new egg matures each month. Men, on the other hand, produce millions of sperm cells every time they ejaculate. After each ejaculation, they must literally replicate those cells, and each replication multiplies the chance for a DNA "copy error"—a genetic chink in the sperm DNA. The more ejaculations a man produces, the greater the chance for chinks to arise, leading to increased point mutation and thus increased infertility and birth defects. While a woman's reproductive capacity halts more or less abruptly after all her eggs have been used up somewhere in their forties or fifties, men experience a longer, more gradual winnowing and disintegration. "We believe that something in men's DNA replication machinery keeps becoming less efficient and less accurate with age, and the problems accumulate," says Jabs.
A Chilling Finding
The biggest news—the father's role in brain disorders—has come to light largely because of research from Israel, where birth records routinely include the age of the male parent. The first unsettling finding linked paternal age and schizophrenia.
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