Nicotine exposure during pregnancy increases flu severity later in life
University of California - Santa Cruz
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Exposure to nicotine during pregnancy and shortly after birth can have a lasting impact on a child’s immune system and cause more severe respiratory infections later in life, shows a new study from researchers at the University of California, Santa Cruz.
Prenatal nicotine exposure has long been known to cause a range of health issues, from premature birth to increased respiratory illnesses, but scientists have not clearly understood the processes that cause these vulnerabilities. Now, research published in Stem Cell Reports shows that in mice models, nicotine exposure during pregnancy and just after birth alters the stem cells that create the body’s blood cells and other crucial lung immune cells. This leads to increased susceptibility and severity to influenza, and likely other respiratory diseases, later in life.
"This study is not on all the compounds you inhale while smoking a cigarette, it is really on the addictive compound nicotine,” said Marcel Rommel, a study author and postdoctoral researcher at UC Santa Cruz. “During pregnancy, clinicians sometimes recommend nicotine replacement therapy, such as patches or gum, to help patients quit smoking. These products still contain nicotine, and our study suggests that nicotine itself negatively affects the development of the immune system.”
Isolating nicotine’s impact
This research was led by Professor of Biomolecular Engineering Camilla Forsberg’s lab at the Institute for the Biology of Stem Cells (IBSC) and the Baskin School of Engineering. The lab focuses on blood stem cell development and disease from embryonic development to aging, and the impact of environmental exposures, positive or negative, on blood system health throughout life.
Cigarettes, other tobacco products, and newer alternatives such as vapes and nicotine pouches, contain nicotine alongside other potentially harmful substances, making it difficult to separate nicotine’s effects from those of other ingredients. Supported by funding from the UC tobacco-related disease research program, the researchers decided to look at the impact of nicotine on its own, particularly as nicotine is consistently the addictive compound found in more modern tobacco products as cigarette use declines.
“We want to translate the research that we do in the lab to people's well-being,” said Alessandra Rodriguez y Baena, study author, Forsberg lab Ph.D. alumna, and a current biology professor at Hartnell College. “In the U.S., almost 4% of mothers smoke during pregnancy, and in other countries there are still a lot more than that. Most people know that smoking during pregnancy is harmful, but we still have much to learn about how nicotine affects a developing baby and whether those effects can last into adulthood.”
The researchers used mouse models and cell lineage-tracing tools to understand the effects of perinatal nicotine exposure to blood-forming stem cells, which are crucial to the immune system.
They found that offspring exposed to nicotine were born with fewer blood-forming stem cells, called hematopoietic stem cells (HSCs). These cells showed altered patterns of immune regulator genes, which persisted into adulthood, even though nicotine exposure ended shortly after birth.
“These cells are reduced after exposing these mice to nicotine, which could be a reason why epidemiological studies have shown that children are more susceptible to respiratory tract infections,” Rommel said. “This could tell us why—it’s really an impact in the cellular space. Even more than just being exposed to smoke, it might be the nicotine received during pregnancy.”
Long term effects
Into adulthood, the changes in blood cells appeared to be reduced. However, their lungs had fewer resident macrophages, the key immune cells that essentially clean up the lungs and act as a first line of defense against pathogens.
“HSCs exposed to nicotine during embryonic development end up being diminished, and we're not specifically sure why, but there's a change in a different direction than if you expose the mice to nicotine during adulthood,” said Taylor Cool, who started the project as a Ph.D. student in the Forsberg lab and is now a program manager at the UC Santa Cruz IBSC. “Adult HSCs respond differently than fetal HSCs, which is really interesting.”
Although adult HSC seemed to rebound into adulthood, further testing showed that heightened disease severity appears to be a lasting impact of nicotine exposure. The researchers tested the impact of an influenza infection on the nicotine-exposed mice, in collaboration with members of UC Santa Cruz Assistant Professor of Molecular, Cell, and Developmental Biology David Boyd’s lab, which studies respiratory viral infections.
During influenza infection, they found increased inflammation in the lungs and greater movement of immune cells to this area, which led to more severe lung damage and greater weight loss. This supports the idea of cellular memory—that a primary exposure to something trains the immune system positively or negatively, and impacts secondary exposures later in life.
“Cells can have this memory, but don’t show it, until the second hit,” Rommel said. “We want to follow up on this—what is this memory, and where is it in the cells?”
The researchers anticipate that a similar exaggerated response would be seen with other respiratory viruses or bacterial infections, like pneumonia or RSV. Taken together, the researchers hope that this study might offer support for protective public health measures.
“Our findings suggest that the environment we are exposed to early in life can have lasting effects on the immune system,” Rodriguez y Baena said. “We studied influenza, which we can get vaccinated against. So the next question is, ‘Can we reduce the harmful effects of these early exposures through public health measures?’ Understanding these early exposures can help us find ways to protect people later in life from the consequences of exposures they had no control over.”
This study unfolded over more than five years, guided by the ranging and interdisciplinary expertise of researchers at the Forsberg lab and at UC Santa Cruz.
“This project is a really good example of how different perspectives and researchers’ experiences can help guide the next questions,” Rodriguez y Baena said. “We did experiments, we let the data tell its story, but then the next questions we were able to ask because of the multiple people that were participating in that project and their own experiences.”
Journal
Stem Cell Reports
Article Title
Perinatal Nicotine Exposure Disrupts Hematopoietic Stem Cell Development and Elevates Influenza Severity in Adulthood
Article Publication Date
15-Oct-2026
Early nicotine exposure leaves a lasting effect on the immune system
Nicotine exposure during pregnancy and shortly after birth caused lasting changes to the blood-forming stem cells and the developing immune system in mice, including a more damaging response to influenza infection later in life, researchers found.
The research team, led by Camilla Forsberg at the University of California, Santa Cruz, USA, exposed pregnant mice to nicotine to investigate the effects of perinatal nicotine exposure (PNE) to the blood building system. The researchers found that offspring exposed to nicotine had fewer blood-forming stem cells, the cells that produce mature effector immune cells and altered patterns of immune regulatory genes within these cells. These changes persisted into adulthood, even though nicotine exposure ended shortly after birth. The findings were published today in Stem Cell Reports.
The immune damage was largely invisible under normal conditions in adult mice. Exposed mice had normal numbers of immune cells circulating in their blood. However, their lungs had fewer resident macrophages,, immune cells that provide an important first line of defense against pathogens. When the PNE mice were later infected with influenza virus, their immune systems responded with increased inflammation and greater movement of immune cells into the lungs. This heightened response resulted in more severe lung damage and greater weight loss.
“This shows how sensitive the developing blood system is to its environment.” said Marcel Rommel, Ph.D. “Blood stem cells set the balance of the immune system, and they carry a memory of what they encountered early in life. An exposure in the first weeks of life can tip that balance in a way that stays hidden until the body faces an infection, and that shapes immune health well into adulthood. The best protection is avoiding nicotine during pregnancy, but we also want to understand whether these changes can be counteracted once they have occurred.”
Smoking during pregnancy is known to negatively affect fetal development, including development of the immune system. Children born to mothers who smoke during pregnancy, for example, are more likely to experience respiratory infections, which can also be more severe.
Tobacco smoke contains many harmful substances in addition to nicotine, making it difficult to determine the effects of nicotine alone. This study helps address that question by isolating nicotine exposure in a mouse model. The findings suggest that nicotine itself can disrupt immune development and have effects that persist long after exposure ends.
“What happens during early development can shape health for a lifetime,” said Taylor Cool, Ph.D. “Our findings show how perinatal nicotine exposure can permanently alter the stem cells responsible for building the immune system. Our study highlights how exposure during this critical window can have lifelong consequences for health.”
While findings in mice do not necessarily translate directly to people, the research raises important questions about nicotine exposure during pregnancy and early development, including through products such as e-cigarettes and nicotine replacement therapies.
About Stem Cell Reports
Stem Cell Reports is the open access, peer-reviewed journal of the International Society for Stem Cell Research (ISSCR) for communicating basic discoveries in stem cell research, in addition to translational and clinical studies. Stem Cell Reports focuses on original research with conceptual or practical advances that are of broad interest to stem cell biologists and clinicians. Stem Cell Reports is a Cell Press partner journal. Find the journal on X: @StemCellReports.
About ISSCR
Across more than 80 countries, the International Society for Stem Cell Research is the preeminent global, cross-disciplinary, science-based organization dedicated to advancing stem cell research and its translation to medicine.
Journal
Stem Cell Reports
Article Title
Perinatal Nicotine Exposure Disrupts Hematopoietic Stem Cell Development and Elevates Influenza Severity in Adulthood
Article Publication Date
15-Oct-2026
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