DETROIT – Researchers at the Wayne State University School of Medicine’s C.S. Mott Center for Human Growth and Development have been awarded a five-year, $2.4 million grant from the National Institute of Environmental Health Sciences of the National Institutes of Health to study how exposure to e-cigarette components and flavors during pregnancy affect fetal respiratory immune development and the risk of respiratory viral infections in offspring.
The grant was awarded to Dr. Jayanth Ramadoss, professor of Obstetrics and Gynecology and director of the Pregnancy and Environment Division at the C.S. Mott Center for Human Growth and Development, who will serve as lead principal investigator, and Dr. Marta Rodriguez-Garcia, associate professor of Biochemistry, Microbiology and Immunology at the Wayne State University School of Medicine. They will serve as multiple principal investigators.
Electronic cigarette use during pregnancy represents a growing public health concern, in part because of the perception that e-cigarettes as less harmful than traditional cigarettes. However, increasing evidence suggests e-cigarette exposure during pregnancy may adversely affect fetal development and contribute to long-term health consequences for offspring. Despite these concerns, there remains a critical gap in understanding how gestational e-cigarette exposure affects the developing lung immune system and the ability of newborns to respond to respiratory viral infections.
The newly funded project will examine how different components of e-cigarette aerosols alter fetal pulmonary immune development in a sex-specific manner. In particular, the investigators will study the effects of acid, base and salt, components used in newer-generation e-cigarette products. Preliminary studies from the Ramadoss laboratory have shown that prenatal exposure to these compounds can disrupt innate immune pathways in the fetal lung, including viral-sensing pathways, type I interferon signaling and neutrophil-related immune responses. These changes were observed to differ between male and female offspring and were associated with increased susceptibility to neonatal viral infection.
“This project addresses an urgent and timely question in maternal and child health,” Dr. Ramadoss said. “Electronic cigarettes are often viewed as a safer alternative to combustible cigarettes, but our preliminary findings suggest that exposure during pregnancy can alter the developing lung immune environment of the fetus. Understanding these effects is essential if we are to protect newborns from respiratory complications later in life.”
The research team will use complementary approaches, including preclinical pregnancy models, advanced vaping exposure systems that mimic human use, spectral flow cytometry, confocal imaging, single-cell RNA sequencing, computational modeling and neonatal viral infection models. The first aim of the project will be to define how gestational exposure to e-cigarette components affects fetal lung immune cells, including neutrophils, macrophages, NK cells and alveolar epithelial cells. The second aim will use single-cell transcriptomics, advanced computational modeling, machine- and deep-learning approaches to identify the gene networks and signaling pathways disrupted by e-cigarette exposure. The third will test if postnatal treatment with interferon beta can improve antiviral responses and the disrupted gene-gene networks in newborns exposed to e-cigarette components during pregnancy.
A major innovation of the study is its focus on biological sex as a determinant of fetal immune programming. Early data indicate that male and female fetal organs respond differently to gestational e-cigarette exposure, suggesting that the long-term consequences of prenatal vaping may not be the same for all offspring. By identifying sex-specific mechanisms of immune disruption, the project may help inform future preventive or therapeutic strategies tailored to the needs of newborns at increased risk for respiratory infection.
“Our goal is to understand how prenatal environmental exposures shape the immune system before birth,” Dr. Rodriguez-Garcia said. “By combining reproductive biology, immunology, virology and systems-level approaches, we can begin to define how e-cigarette exposure affects the developing fetal organs and whether targeted interventions can restore protective antiviral responses after birth.”
The grant reflects the growing national interest in understanding how environmental exposures during pregnancy influence child health and development. It also builds on the C.S. Mott Center’s long-standing strength in reproductive biology, pregnancy research, environmental health, fetal programming and sex differences in disease susceptibility.
“The work of Drs. Ramadoss and Rodriguez-Garcia is an excellent example of the mission of the Mott Center,” said Gil Mor, M.D., Ph.D., scientific director of the center and vice chair for Research in the Department of Obstetrics and Gynecology. “This project integrates environmental toxicology, pregnancy biology, fetal development, immunology and child health. It also addresses a critical clinical question: How exposures before birth may alter the health of the next generation. This is precisely the type of interdisciplinary and translational research that the Mott Center was designed to support.”
The findings from this project may provide important new insight into how prenatal exposure to e-cigarette aerosols affects fetal lung immune environment and neonatal susceptibility to respiratory viral infection making use of novel gene network modeling approaches. Ultimately, the research may contribute to improved counseling, prevention strategies and future interventions aimed at protecting infants exposed to e-cigarettes during pregnancy.
“This crucial research being done right here in Detroit is investigating a growing public health challenge,” said Dr. Ezemenari M. Obasi, vice president for research & innovation at Wayne State University. “Drs. Ramadoss and Rodriguez-Garcia’s research will bridge cutting-edge science with real-world health outcomes to empower expectant mothers and healthcare providers with vital insights needed to protect our community’s most vulnerable future generations.”
The C.S. Mott Center for Human Growth and Development at Wayne State University is a nationally recognized multidisciplinary research center dedicated to advancing discoveries in reproductive biology, pregnancy, fetal development, cancer, environmental health and the developmental origins of disease. Through collaborative basic, translational and clinical research, the center seeks to improve the health of women, children and families while training the next generation of biomedical scientists.
Acknowledgment and Disclaimer: Research cited in this article was supported by the National Institute of Environmental Health Sciences of the National Institutes of Health under award number R01ES038818. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
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