Wednesday, April 24, 2024
4/24/2024
Growing evidences 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-fetal health, with implications for preterm birth, children sensitivity to infections, asthma and other adverse health outcomes. The central theme of this application 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. Our central hypothesis is that inflammation in the placenta and decidua due to maternal exposure to VOCs, alters the programming of the fetal immune system, which results in an aberrant post-natal immune response to respiratory viral infections. Our 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 and how indirect training by the maternal inflammation takes place is unclear and understudied. Our specific aims are: Aim 1. To determine the effect of VOCs maternal exposure on placental and fetal inflammation. Aim 2. To determine the impact of VOCs exposure on TLR signaling responsible for the homing and differentiation of T and B cells. Aim 3. Characterize the signals from the placenta responsible for the susceptibility to respiratory viral infections of the offspring. Upon completion of these aims we will have 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. Adequate response to infection is the result of a delicate balance between an efficient immune response against pathogens and its quick resolution preventing widespread over-activation. The cellular and molecular components of this regulatory balance are determined during fetal development.
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