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.”
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.”
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.”
Stem Cell Reports
Perinatal Nicotine Exposure Disrupts Hematopoietic Stem Cell Development and Elevates Influenza Severity in Adulthood
15-Oct-2026