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Nicotine can wield its effects on offspring in more ways than from exposures in utero or secondhand smoke: the sperm of mice that ingested nicotine carry epigenetic signatures of that exposure, a study published in PLOS Biology today (October 16) reports. The result might explain why the experiments also found the male mice’s offspring—and grandoffspring—exhibited abnormal behavior and learning impairments.

“Until now, much attention had been focused on the effects of maternal nicotine exposure on their children,” Florida State University’s Pradeep Bhide, who led the study, tells The Boston Globe in an email. “Not much had been known about the effects of paternal smoking on their children and grandchildren. Our study shows that paternal nicotine exposure can be deleterious for the offspring in multiple generations.”

To investigate paternal exposure, Bhide’s team spiked male mice’s drinking water with nicotine for 12 weeks. The researchers then bred those animals with unexposed females, and mated the offspring to produce the third generation.

The second- and third-generation mice underwent a battery of cognitive and behavioral tests to see if their father’s or grandfather’s nicotine exposure had any effect. On some examinations, the mice performed typically, but they didn’t do as well on certain learning tasks as mice whose parent or grandparent had not been given nicotine. The second generation also exhibited hyperactivity and had lower levels of certain neurotransmitters in the brain than the offspring of unexposed animals had.

The results “are consistent with the clinical presentation, putative neurobiological mechanisms, and rate of diagnosis of ADHD and autism,” the authors write in their report.

In search of a possible mechanism for the transgenerational effects of nicotine, the investigators assessed methylation on the sperm genome of exposed and unexposed mice, finding fewer such epigenetic markers in the nicotine-treated animals.

Scientists expressed uncertainty over the ability to extrapolate these results to humans, in part because the mice in the study “were forced to absorb what for them are huge doses of nicotine,” Peter Hajek, director of the Tobacco Dependence Research Unit at Queen Mary University of London, tells Newsweek. “Such studies rarely translate to human smokers.”