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Findings from studies conducted by researchers at Florida State University's College of Medicine suggest that exposure to nicotine in men could lead to cognitive deficits in their children and grandchildren. Research has shown that the addition of nicotine to the drinking water of male mice has resulted in epigenetic changes in sperm genes that may impact the major pathways of neurodevelopment. The immediate offspring of these male mice exposed to nicotine exhibited hyperactivity, attention deficit, and cognitive problems typical of those encountered in Attention Deficit Hyperactivity Disorders (Figure 2). ADHD) and the spectrum of autism in humans. The grandchildren of fathers exposed to nicotine also exhibited learning deficits, suggesting that at least some of the nicotine-related adverse effects can be passed down from generation to generation.
"Our data raise the possibility that some of the cognitive impairments found in the current generation of children and adults are attributable to the environmental damage suffered for a generation or two," suggests Pradeep Bhide, Ph.D. .D., Jim and Betty Ann Rodgers eminent chair of developmental neuroscience specialist at the College of Medicine at Florida State University. "Smoking was more common and more easily accepted by the population in the 1940s, 1950s, and 1960s than today, and could this exposure be a marked increase in the number of diagnoses of neurodevelopmental disorders such as ADHD and autism? "
The team at Florida State University and colleagues at Harvard Medical School published their findings in PLOS Biologyin an article entitled "Exposure of male mice to nicotine causes behavioral problems in several generations of offspring".
Studies have shown that nicotine use by pregnant women is associated with an increased risk of behavioral problems in their children and in subsequent generations, the authors write. But in reality, smoking is more prevalent among men than women and, although studies in humans have suggested that parental cigarette use may increase the risk of ADHD in their children, " Studies in humans can not completely separate the effects of smoking in parents. Environmental factors. ADHD and nicotine addiction often go hand in hand, and ADHD is common in families, so it is difficult to separate the role of paternal ADHD from paternal smoking on behavioral changes seen in offspring.
To study the effects of paternal nicotine on offspring, the team exposed male nicotine mice in their drinking water for 12 weeks, then raised them with naive females to the drug. Male and female offspring (F1) were then raised with drug-naive partners to produce a second generation (F2) of animals from fathers exposed to nicotine.
Tests in the resulting litters showed that the F1 offspring of nicotine-exposed fathers, both male and female, exhibited increased spontaneous locomotor activity and deficits in inversion learning. Male offspring also had "significant deficits in attention, monoamine content in the brain and dopamine receptor mRNA expression," the team said. And while the hyperactivity and attention deficit phenotypes observed in F1 mice were not transmitted to second-generation offspring, male F2 mice had deficits in inversion learning.
An examination of the spermatozoa of fathers exposed to nicotine showed changes in overall DNA methylation, and in particular, changes in DNA methylation at the promoters of the D2 dopamine receptor gene. Dopamine receptors play a key role in neurodevelopmental processes. "The methylation of nicotine-induced sperm DNA at the dopamine receptor-promoting regions could be a plausible epigenetic mechanism of transgenerational transmission of the effects of paternal exposure to nicotine," suggest authors.
"By analyzing the father's sperm, we found several genes with epigenetic modifications," says Deirdre MCarthy, co-author, PhD student at the Florida State University College of Medicine's Faculty of Research. "This includes the dopamine D2 gene, which plays an important role in the development and learning of the brain.This is probably the source of the cognitive deficits found in their offspring."
The fact that only part of the apparent deficits in F1 offspring was also detected in F2 male offspring suggests that "at least some of the deleterious effects of nicotine exposure may be transient", they continue, although the team recognizes that more research will be needed. necessary. "These findings underscore the need to broaden the current focus of research and public policies targeting the exposure of pregnant women to nicotine by putting more emphasis on exposure." from mother and father to nicotine. "
"I think the results of our study can be extrapolated to humans," adds Dr. Bhide. "Doctors can not warn men that their smoking could harm their unborn child, even if his mother has never smoked." I believe our study puts that in the foreground.
In recent weeks, researchers at Wexner Medical Center at Ohio State University have independently reported studies on mice, which showed that a father's level of physical activity prior to conception could have lasting effects on the metabolic health of his children. A team led by Kristin Stanford, Ph.D., assistant professor at Ohio State University, raised obese, fat-rich, diet-fed mice that were either sedentary or had free access to wheels with female mice fed a normal diet. diet. They found that while the offspring of sedentary obese fathers had more fat and increased glucose intolerance than fathers fed normal diets, paternal exercises suppressed the effects of the high-fat father's diet. and that their offspring showed better glucose metabolism, reduced body weight, and reduced body fat.
"This is really interesting," says Dr. Stanford. "The children of fathers fed a high-fat diet had fewer results, so they were more glucose intolerant. But exercise has negated this effect. When the father did exercise, even with a high-fat diet, we found an improvement in the metabolic health of their adult offspring. "
An examination of fathers' sperm showed that the high-fat diet was associated with decreased sperm motility and multiple changes in the small sperm RNA, which could be reversed by physical training. … We have seen a big change in their small RNA profile, "says Dr. Stanford. We now want to know exactly which small RNAs are responsible for these metabolic improvements, where this happens in the offspring and why.
Studies have been reported in Diabetes ("Paternal exercise improves glucose metabolism in adult children"). Researchers at Ohio State University believe that their mouse studies could be of direct interest to humans. "It's possible that this translates to humans," says Dr. Stanford. "We know that in adult men, obesity alters testosterone levels, sperm count and motility, as well as the number of live births … If we ask someone who is preparing to Having a child who exercises moderately, even one month before conception, may have a significant effect on the health of his sperm and the long-term metabolic health of his children. "
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