Prenatal Exposures and Later-Life Health Effects: Promoting Research on Fetal and Developmental Origins of Health and Disease
Superfund Research Program (SRP) researchers are taking a variety of approaches to examine how exposures to potentially harmful chemicals in the womb or early in life may impact development and play a role in later-life consequences. These approaches include studies involving human populations and the use of model organisms, such as mice and zebrafish.
Studies in cells, model organisms, and large populations can complement each other and provide insight into how changes to proteins or other pathways in the body may affect health down the road. This knowledge may help us understand the best ways to reduce exposures to potentially harmful chemicals and prevent disease. SRP researchers also address how to reduce these exposures by developing tools and methods to clean up environmental contaminants or reduce contaminant availability or toxicity.
Large-scale studies in humans: finding associations in human populations
Large cohort studies track populations over time and may help determine risk factors for disease, such as exposures to harmful pollutants. Using cohorts, SRP researchers are measuring or estimating early-life exposures to contaminants and examining later life outcomes. This provides information linking exposures and disease that can be explored further in mechanistic studies.
For example, researchers at the University of California, Berkeley SRP Center, led by Craig Steinmaus, M.D., are studying the effects of early-life exposure to arsenic in a group of people in northern Chile. In 1958, river water containing high arsenic concentrations was diverted to this region. After discovery of the high arsenic levels and the installment of a water treatment plant in 1970, the arsenic concentrations in drinking water were drastically reduced.
SRP researchers have followed this uniquely exposed population to see how high exposure to arsenic in drinking water during a brief window early in life may be associated with later life health effects. Studying this exposed cohort has provided evidence that in utero and childhood arsenic exposure are associated with signs and symptoms of lung disease in adults, such as decreases in lung capacity and increases in chronic cough and bronchitis. They also linked early-life arsenic exposure to cancer in specific kidney and ureter cells as well as lung and bladder cancer.
A cohort with a separate unique situation is being followed by Boston University SRP Center researchers, led by Ann Aschengrau, Sc.D. From 1968 to 1983, widespread tetrachloroethene (PCE) contamination of public drinking water supplies occurred in the Cape Cod region of Massachusetts. The source of the contamination was a vinyl liner applied to the inner surface of water distribution pipes.
Researchers initiated the Cape Cod Health Study to examine possible health consequences of prenatal and early childhood exposure to PCE-contaminated drinking water. The research revealed that prenatal and early-life exposure to PCE was associated with decreased performance on learning and memory tests as well as elevated risk of mental illness, including post-traumatic stress disorder and bipolar disorder.
Studies in cells and animal models: identifying how chemicals may impact development
Researchers use studies in cells and other organisms to examine changes in DNA, genes, and neurons that may reveal how an exposure could affect fetal and early childhood development. These changes also may be linked to behavioral changes in model organisms. Although findings from cell and animal studies may not directly translate to humans, they provide evidence of potential effects and help guide further study.
For example, researchers led by Robert Tanguay, Ph.D., at the Oregon State University (OSU) SRP Center are using zebrafish to examine how early-life exposure to benzopyrene (BaP), a common polycyclic aromatic hydrocarbon (PAH), may be linked to behavioral changes. Common sources of BaP include wood burning and coal tar. In a recent study, they found that exposure to BaP during development led to impaired adult learning and memory deficits in zebrafish. In another study, they found that bisphenol A (BPA), a chemical produced for use primarily in the production of polycarbonate plastics and epoxy resins, impairs sperm function and reproduction in zebrafish.
At the Duke University SRP Center, researchers led by Theodore Slotkin, Ph.D., evaluated the neurodevelopmental effects of a PAH mixture obtained from the Elizabeth River Superfund site and of BaP, a single PAH in the mixture. Using cell-based tests, they found that neural stem cells were less likely to change into glia, which support and protect neurons in the brain, when exposed to the PAH mixture compared to BaP alone, which can affect brain homeostasis and function. They also found that brain cells were more sensitive to BaP than the PAH mixture at a later point in neurodevelopment, when the cells transition into neurons.
According to the researchers, the differences between the effects of PAH mixtures and BaP at two separate points in neurodevelopment may be a result of interactions among mixture components. Additionally, the potential health effects of PAHs may extend throughout fetal brain development and into early childhood.
In a separate endeavor, researchers at the University of Arizona SRP Center examined the relationship between arsenic exposure and metabolic disease in mice. They found that in utero and continuous early-life exposure to arsenic disrupted normal metabolism and elevated the risk for fatty liver disease in mice maintained on a high-fat diet. According to the authors, their findings suggest that individuals exposed to arsenic during key developmental periods – and who remain exposed to arsenic while on a Western-style diet – may be at increased risk for metabolic disease later in life.
Strategies to reduce exposures
Alongside mouse and large-scale human studies related to the effects of arsenic, SRP grantees are studying how to remediate, or clean up, arsenic in the environment. For example, researchers led by Steven Chillrud, Ph.D., at Columbia University are investigating how injection of chemical additives may accelerate the remediation of arsenic.
Researchers at the University of Tennessee, led by Frank Loeffler, Ph.D., are examining how chemical modifications to helper molecules, such as vitamin B12, may affect how well some bacteria degrade toxic chlorinated pollutants like PCE. A better understanding of the chemical conditions that produce these forms of the helper molecules could help improve cleanup of chlorinated contaminants at hazardous waste sites.
In addition to looking at the behavioral effects of PAHs, SRP researchers are exploring ways to clean them up and to ensure that products from remediation are not more toxic than the parent compound. For example, University of North Carolina at Chapel Hill SRP Center researchers, led by Michael Aitken, Ph.D., are using bioreactors to simulate environmental conditions to examine how adding low levels of surfactants, which are commonly used as dispersing agents, may be a promising method to maximize removal of PAHs at hazardous waste sites.
For more on how SRP researchers are reducing exposures to hazardous substances and improving public health through prevention and intervention strategies, see the February 2017 Science Digest Feature.