Category: Model

  • New Model Could Help Provide Expectant Mothers a Clearer Path to Safe Fish Consumption

    New Model Could Help Provide Expectant Mothers a Clearer Path to Safe Fish Consumption

    Fish consumption during pregnancy is a complex scientific topic. On one hand, fish are rich in nutrients essential to brain development, including polyunsaturated fatty acids, selenium, iodine, and vitamin D. On the other, fish contain methyl mercury, a known neurotoxicant. This has led the US Food and Drug Administration to recommend that expectant mothers limit consumption, which inadvertently causes many women to forgo fish consumption during pregnancy altogether.

    Fish consumption is an important route of methyl mercury exposure, however, efforts to understand the health risk posed by mercury are further complicated by the fact that the nutritional benefits from fish may modify or reduce the toxicity posed by mercury. A new study appearing in the American Journal of Epidemiology based on data from a cohort of residents of a coastal community in Massachusetts creates a new framework that could untangle these questions, reduce confusion, and produce clearer guidance on fish consumption for pregnant mothers.

    “We propose an alternative modelling approach to address limitations of previous models and to contribute thereby to improved evidence-based advice on the risks and benefits of fish consumption,” said the authors, who include Sally Thurston, PhD, with the University of Rochester Medical Center, Susan Korrick, MD, MPH, with Harvard T.H. Chan School of Public Health and Brigham and Women’s Hospital, and David Ruppert, PhD, with Cornell University. “In fish-eating populations, this can be addressed by separating mercury exposure into fish intake and average mercury content of the consumed fish.”

    The new research comes from an analysis of data from the New Bedford Cohort, which was created to assess the health of children born to mothers residing near the New Bedford Harbor Superfund site in Massachusetts. The current study included 361 children from the cohort who were born between 1993 and 1998 and underwent neurodevelopment assessments, including tests for IQ, language, memory, and attention, at age eight years.

    The researchers were able to measure mercury exposure during the third trimester of pregnancy through hair sample collected from the mothers after birth. While hair samples have been the traditional method to study maternal mercury exposure, this approach alone cannot distinguish between mothers who frequently consumed low-mercury fish compared to those who consumed a smaller quantity of high-mercury fish.

    To overcome this limitation, the researchers instead created a model that includes estimates of mercury exposure per serving of fish. This was possible because mothers in the cohort also completed a food questionnaire and reported the type and frequency of fish and shellfish consumed during pregnancy. The authors estimated the average mercury levels by type of fish, and when combined with the information about the mother’s diet, they were able to create a more precise and detailed method to estimate the joint associations of pregnancy fish intake and fish mercury levels on neurodevelopment.

    Using this model, the researchers found that the relation between pregnancy fish consumption and subsequent neurodevelopment varied depending on the estimated average mercury levels in the fish. Specifically, consuming low mercury-containing fish was beneficial, while consuming fish with higher levels of mercury was detrimental.

    “Given methodologic limitations to previous analyses, future work expanding our alternative modelling approach to account for both the average mercury and nutritional content of fish could facilitate better estimation of the risk-benefit tradeoffs of fish consumption, a key component of many healthy diets,” said the authors.

    The authors are in the process of applying this model to other large studies of maternal fish consumption, including the Seychelles Child Development Study, which Thurston serves on as an investigator.

    The American Journal of Epidemiology study was supported with funding from the National Institute of Environmental Health Sciences.

  • New 3D Model Shows How Cadmium Exposure May Affect Heart Development

    New 3D Model Shows How Cadmium Exposure May Affect Heart Development

    Researchers have developed a three-dimensional model that shows how exposure to cadmium might lead to congenital heart disease. Affecting nearly 40,000 newborns a year, congenital heart disease is the most common type of birth defect in the United States. The model was created by scientists at the National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health.

    Cadmium is a metal that can be released into the environment through mining and various industrial processes, and it has been found in air, soil, water, and tobacco. The metal can enter the food chain when plants absorb it from soil. Previous studies suggested that maternal exposure to cadmium might be a significant risk factor for congenital heart disease.

    Using models derived from human cells and tissues, called in vitro models, researchers designed a 3D organoid model that mimics how the human heart develops. The researchers saw how exposure to low levels of cadmium can block usual formation of cardiomyocytes, which are the major type of cells that form the heart. In doing so, they revealed the biological mechanisms that might explain how cadmium could induce heart abnormalities.

    “The models we created are useful for not only studying cadmium, but for studying other chemicals and substances as well,” said study lead Erik Tokar, Ph.D., from the Mechanistic Toxicology Branch of the NIEHS Division of Translational Toxicology (DTT).

    For the study, the researchers developed three different models to evaluate the effects of cadmium on different stages of heart development.

    First, they used human pluripotent stem cells to develop 3D embryoid bodies to mimic early steps in tissue and organ formation in humans. They then used a 2D in vitro model that included a fluorescent regulatory protein system (NKX2-5) known to be involved in heart development, which allowed them to look at cadmium toxicity after exposure.

    The 3D cardiac organoid model, which can simulate the beating heart, confirmed what was seen in the other two models, showing how low doses of cadmium can inhibit the cardiomyocytes from functioning properly.

    The study, published in the journal Environmental Health Perspectives, builds on decades of work by toxicology researchers to advance knowledge about how environmental exposures may contribute to human diseases including cancer, cardiovascular disease, autism, and other conditions.

    “These new models are leveraging advances in technology that allow us to model human biology in a way that identifies real human health hazards,” noted Brian Berridge, D.V.M., Ph.D., scientific director, DTT. “They also help reduce our reliance on animal testing.”

    “We found that early exposure to human-relevant levels of cadmium lead to a dramatic inhibitory effect on cardiomyocyte differentiation, whereas later stage exposures did not have this effect,” said Xian Wu, Ph.D., who conducted these studies. “This cadmium exposure also damaged the cardiac organoid functionality.”

    Grants: This research was supported by the Intramural Research Program (Translational Toxicology Division) of the NIH, NIEHS (ZIAES102925).

    Reference: Wu X, Chen Y, Hu G, and Tokar EJ. 2022. Cardiac Development in the Presence of Cadmium: An in vitro Study Using Human Embryonic Stem Cells and Cardiac Organoids. Environmental Health Perspectives. [Full Text Wu X, Chen Y, Hu G, and Tokar EJ. 2022. Cardiac Development in the Presence of Cadmium: An in vitro Study Using Human Embryonic Stem Cells and Cardiac Organoids. Environmental Health Perspectives.]