Project Summary (2022-2027)

Among the 100 American cities with the greatest number of births, Detroit has the highest reported preterm birth (PTB) rate of 15.2 percent. The etiologic factors that play central roles in this public health emergency are currently unknown. However, evidence suggests that exposure to volatile, very volatile, and semi-volatile organic compounds (collectively abbreviated VOCs) during vulnerable life windows of susceptibility is an important determinant of maternal-offspring health, with implications for PTB and associated adverse health outcomes. The Center for Leadership in Environmental Awareness and Research (CLEAR) is dedicated to understanding and mitigating this serious environmental health problem. The central theme of this project focuses on deciphering the signaling pathways by which exposure to VOCs during pregnancy have an impact on early life growth and development with a focus on the fetal immune system.

The researcher’s central hypothesis is that inflammation in the placenta and decidua due to maternal exposure to VOCs, alters the development of the fetal immune system, which results in an aberrant post-natal immune response to infections. Their preliminary studies suggest that although the fetus may be protected against microbial infection, the outcome of maternal exposure, protective or deleterious, depends on the nature of the immune response and the severity of the inflammatory process at the implantation site (placenta-decidua interface). The mechanisms underlying the response of the fetal immune system to VOC exposure and how indirect training by VOC-induced maternal inflammation takes place is unclear and understudied.

The project’s specific aims are:

• Determine the effect of BTEX maternal exposure on placental and fetal inflammation.
• Determine the impact of VOCs exposure on TLR signaling responsible for the homing and differentiation of T and B cells.
• Characterize the offspring immune responses of pups from mothers with VOCs exposure to microbial infection.

This research will lead to a better understanding of the outcomes associated with the impact of VOCs exposure on the placental/decidua unit and its consequent influence on fetal programing and its potential effects on the development of an appropriate neonatal immune responses. This project is a mechanistic bridge between the Developmental VOC Exposure in Zebrafish: Toxic Mechanisms and Biomarkers and Epidemiological Study of Volatile Organic Compounds and Preterm Birth in Detroit projects that utilizes a placental model of inhalational VOC exposure. The Chemical Analysis Core quantitates BTEX metabolites and the Data Management and Analysis Core disseminates data among the biomedical projects to make comparisons between fish, mouse, and human exposures paradigms possible. This project informs future epidemiological studies that investigate associations between maternal VOC exposures and inflammatory outcomes in children such as asthma.