Father’s health just as vital
New scientific focus revealing that paternal lifestyle choices can affect health of babies for generations
When my daughter became pregnant with my grandson last year, she stopped drinking. Had she been a smoker, she would have forsworn her Marlboros. Her husband, on the other hand, was free to lift a glass and light up if he so chose. Or was he?
The belief that a pregnant woman is responsible for the well-being of her fetus is easy to understand. A fetus is (literally) connected to its mother. Myriad factors such as a mother’s physical and mental condition, exposure to toxins and whether she is well-nourished have long been recognized as determinants of newborn fitness. Yet the paternal role in producing a healthy baby is rarely considered. That’s unfortunate because emerging science indicates that fathers play a more significant role in pregnancy outcomes than previously thought.
Moreover, both parents need to start thinking about what they eat and how they live their lives well before they decide to conceive.
Traditionally, the father’s role in reproduction focused on the preconception period — whether his sperm was potent enough to fertilize the female egg. These days, thanks to a decadeslong decline in sperm counts, such concerns have moved to the front burner. The evidence that environmental toxins, especially endocrine disrupters (chemicals often found in common items such as personal-care products and plastic containers), may contribute to male infertility is compelling. Lifestyle habits such as smoking and excessive alcohol intake as well as nutrient-deficient diets have also been linked to sperm robustness.
The question is, do low sperm counts or damaged sperm actually have an impact on pregnancy outcomes? The answer is yes. For instance, we know that sperm helps to determine how well the placenta forms — a key factor in fetal development — and that impaired sperm dramatically increases the likelihood of miscarriage, possibly because it is known to contain high levels of free radicals. Moreover, thanks to the science of epigenetics, we are learning that human sperm may carry “biological memories” of abnormalities that can be transferred to offspring. In the case of exposure to certain endocrine disrupters, for instance, rodent studies have shown that the effects are transferred by sperm to more than 90% of male descendants, through three generations.
Here’s how it works. A variety of environmental impacts (stress, toxic exposure and poor nutrition are three key ones) trigger changes not in genes themselves, but in how they are expressed. These changes, known as epigenetic modifications, leave chemical marks on genes that are transferred to future generations through sperm (and egg) cells. This process is known as transgenerational epigenetic inheritance. Although epigenetic inheritance is still being challenged by some geneticists, the research is changing almost by the minute. While there is definitely a stage in fetal development when most epigenetic marks are erased from the zygote, it has become clear that some survive and are passed on as the fetus develops.
Some of the earliest work in the field was conducted by Lars Bygren, a Swedish epidemiologist who used historical data from his hometown of Overkalix to reveal intriguing connections between feast, famine and the long-term health of men in 2001. Bygren was able to show that men whose grandfathers had overeaten in the years just before puberty died six years sooner than those whose grandfathers experienced famine at the same age. He subsequently teamed up with a British geneticist, Marcus Pembrey, and one of their studies showed that young men who smoked just before puberty produced sons who were more likely to be overweight, beginning in adolescence.
In both studies, timing was key. The boys were at the age when their sperm cells — the vessels that would transmit their genetic material — were forming. The studies showed that overindulgence in food or exposure to toxins at this key developmental stage left a biological memory on sperm cells that could be passed on to future generations.
Thanks to technological advances, we are gaining insight into how this happens. Take DNA methylation, for instance. It is the most studied epigenetic process, and research is linking factors such as male obesity, high-fat diets and malnutrition with methylation changes in sperm. We know that these changes have the potential to undermine the health of offspring. For instance, when male mice were fed a lowprotein diet, their sperm was shown to be hypomethylated and their offspring had characteristics associated with metabolic syndrome and nonalcoholic fatty liver disease. The good news is studies have shown good nutrition can improve methylation.
DNA methylation is affected by other factors, including plain old aging. When men get older, the epigenetic patterns in their sperm change. Predictably, these changes have been shown to put a dent in fertility. However, they also affect offspring health. A 2018 study of more than 40 million births published in BMJ found that when fathers were older than 45, their children were 14% more likely to be born prematurely and to have a low birth weight (a biological marker commonly accepted as a risk factor for chronic disease later in life). Perhaps surprisingly, it also found that conceiving a child with an older father raised the mother’s risk of developing gestational diabetes by 28%. Epigenetic changes to sperm may help to explain why older fathers are more likely to produce children with neurological disorders.
These days, most pregnant women are diligent about not drinking alcohol because medical recommendations have consistently advised against it. Meanwhile, a growing body of research is showing that when a father over-imbibes before conception, it can spark epigenetic changes in his sperm that negatively affect the fetus. These include low birth weight, impaired cognitive development, insulin hypersensitivity and immune system problems. Most of these studies have been conducted on mice, but human research has shown that when fathers-to-be drink too much, it increases the risk of miscarriage.
The idea that environmental impacts can affect fetal development, setting the stage for chronic disease to develop later in life, is the basis of a new scientific area known as the developmental origins of health and disease. Not surprisingly, research has focused on mothers. But a father’s biological impact on his offspring’s health is rapidly gaining ground as an equal opportunity topic.
Certainly, young men, like young women, should be made aware that their lifestyle decisions have biological implications that transcend themselves, affecting their children, grandchildren and possibly generations beyond.