| dc.description.abstract | Endocrine-disrupting chemicals (EDCs) are exogenous compounds that can interfere with endocrine signaling, and exposure to these chemicals has been linked to numerous human diseases and disorders. Given the direct impact of EDCs on the endocrine system, which in turn affects the immune system, understanding the mechanisms of EDC-induced immunotoxicity provides potential opportunities for therapeutic intervention. While most research studies examining the relationship between EDCs and the immune system have focused on the cells of the adaptive immune system, our studies have concentrated on exploring the impact of EDCs on innate immunity. The initial development of the immune system begins during fetal development, a period in which most mammals exhibit a heightened sensitivity to the effects of EDC exposure. Unfortunately, consequential of fetal plasticity, developmental exposure to certain EDCs, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), can lead to persistent alterations in fetal programming that impact adult health. TCDD is a common environmental contaminant that is known to disrupt both endocrine and immune functions, yet its impact on the innate immune system remains underexplored. Using an interdisciplinary approach that integrates reproductive immunology, reproductive toxicology, and immunotoxicology, we investigated the impact of in utero exposure to TCDD on adult immune function and reproductive health. Herein, we revealed that adult mice with a history of an in utero TCDD exposure displayed an altered innate immune cell composition in addition to a significantly blunted ability to respond to infection compared to unexposed mice. Furthermore, our studies revealed that exposing human placental macrophages to TCDD in vitro significantly inhibits their antimicrobial functions, which are crucial for placental development and healthy pregnancy outcomes. Together, the original work described herein contributes to the field by increasing the understanding of TCDD-induced immunomodulation, particularly on innate immune cells. This work also underscores the importance of investigating how EDC exposures during development and pregnancy impact the long-term health of offspring. | |
