Smoking's Effects Persist From Grandfather to Grandson, Warn Scientists

In the United States, the FDA warnings on tobacco products target either the general population or women only. There are no warnings specifically geared toward men. The risks of smoking or using tobacco for pregnant women and their children have been clear for a long time, but no one had really considered whether a father’s smoking habit could have an effect on his kids. For too long, we assumed that dads were safe because they didn’t actually carry children.

But a study released Wednesday in Plos Biology shows that some effects of dad’s nicotine use can get passed onto his kids — and to some degree to his grandkids. Pradeep Bhide, Ph.D., director of the Center for Brain Repair at the Florida State University College of Medicine, led a team of scientists who showed that the cognitive effects of nicotine use persisted through three generations of male mice.

In the FDA’s current tobacco warnings, Bhide tells Inverse, there’s “nothing about men smoking at any time.” His paper suggests it’s time for that to change.

Nicotine Derails Generations of Brains

The link between a mother’s nicotine use and cognitive issues like ADHD in her children has been well established, and a few previous analyses of existing data presented a “hint” that a father’s smoking could cause the same issues in his kids, says Bhide. The new study, however, is the first to demonstrate that the link is a robust phenomenon.

In the experiments, Bhide’s team gave 12 male mice nicotine-laced water during the period when they were producing sperm, then mated those mice with females that hadn’t been exposed to nicotine. The kids all showed characteristics like hyperactivity, attention deficit disorder, and cognitive inflexibility, which were tested using tricky mouse tasks called the Barnes Maze and the Y-Maze.

Using females from this generation of mice, the team induced mating with males from a separate, nicotine-free group. Once the babies from that generation grew up, it was clear that the cognitive effects had persisted yet again, but to a lesser degree.

“Not much had been known about the effects of paternal smoking on their children and grandchildren,” says Bhide. “Our study shows that paternal nicotine exposure can be deleterious for the offspring in multiple generations.” But what he wanted to know was how.

Epigenetics

Clearly, nicotine-induced changes in the original “grandfather” DNA were being passed on through the generations, which means that those changes had to be present in the DNA of his sperm. When the team looked at the sperm from the original males, they saw that multiple genes carried “epigenetic modifications” — impermanent physical changes to the DNA that make certain genes more or less usable. They’ve been referred to by scientists as “ornaments on a Christmas tree.”

"We don’t know the answers to all those things.

One of the genes affected by epigenetic modifications was the dopamine D2 gene, which is implicated in brain development and learning.

The team’s hypothesis is that these epigenetic changes, induced by nicotine exposure, were passed on through the original generation’s sperm into the children of the next. The changes persisted to some degree in the DNA of those children, so it’s possible some “decorations” were removed from the DNA Christmas tree, which is why the cognitive problems weren’t as robust in the final generation.

Epigenetics is a relatively new field that is not fully understood. “We don’t know the answers to all those things,” says Bhide.

The Threat to Humans

Some critics, says Bhide, have argued that the findings from his mouse study can’t be applied to humans. “That’s unfortunate, because at least [they could] give it a chance,” he says. “There’s nothing to lose by saying, ‘This could happen, so be careful.’”

"There’s nothing to lose by saying, ‘This could happen, so be careful.’

It’s true that there hasn’t been a human trial showing that nicotine’s effects are passed on through men through the generations. Unfortunately, says Bhide, doing those studies would be “virtually impossible to do, at least in the current population of potential subjects, because smoking and ADHD go hand in hand.” In other words, you can’t say a child has ADHD because their father smoked if you can’t tell whether the father actually had nicotine-induced changes in his sperm or if he was carrying other ADHD-linked genes in the first place.

That said, there’s less direct evidence, largely retrospective interrogations of existing data, showing that paternal nicotine exposure increases the risk of ADHD for kids. “Findings from humans and animal models are quite consistent with respect to maternal nicotine exposure,” says Bhide. “I see no reason why the same would not apply to paternal nicotine exposure studies.”

What Now?

Aside from heeding the usual warnings about smoking causing cancer, Bhide says it’s time for men to consider that nicotine could affect their germ cells — their sperm — and pass on lasting changes to their kids. They should also keep in mind that the findings likely apply to all kinds of nicotine consumption: cigarettes, e-cigarettes, vapes, JUULs, and even chewing tobacco.

It’s not clear how long the epigenetic effects of smoking affect a male’s sperm, so it’s probably safest for prospective fathers to err on the side of caution. “Our study raises the concern to another level,” says Bhide, “father’s smoking status before and at the time of conception!” 

"We may not know what it is — our hypotheses may be wrong — but somehow it is happening.

By demonstrating that cognitive effects in children due to their fathers’ nicotine exposure is a real phenomenon, Bhide and his team have taken the first, important step in figuring out how risky it is for prospective fathers to smoke.

“We may not know what it is — our hypotheses may be wrong,” says Bhide, “but somehow it is happening.”