Gulf War and Health Volume 11: Generational Health Effects of Serving in the Gulf War (2018) / Chapter Skim
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10 Pathophysiologic Research
10 Pathophysiologic Research
Pages 461-470
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The Volume 11 committee believes that to assess the potential long-term generational health effects of deployment exposures, a range of basic research using animal and cellular or mechanistic models will be necessary to complement the health monitoring plan and epidemiologic studies discussed in Chapter 9, thus encompassing a state of the science transgenerational study. This basic and translational research can help elucidate the genetic and epigenetic mechanisms that may be responsible for generational health effects in humans.
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From page 462... ...
studies in animal models of human health outcomes that might help to fill data gaps and improve our understanding of how deployment exposures affect the health of veterans and their descendants. UTILITY OF ANIMAL STUDIES During its review of the epidemiologic and animal toxicology literature described in Chapters 4 through 7, the Volume 11 committee identified research on generational health effects from exposures that are potentially relevant to Gulf War and Post-9/11 veterans, such as organophosphate pesticides.
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are most susceptible to specific exposures. This research should also include developing the following: fit-for-purpose models and reagents for generational studies; genetically engineered induced pluripotent stem cells (iPSCs)
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Studies in this area might focus on the timing of the epigenetic programming of gametes to determine windows of susceptibility for generational effects; fundamental molecular and cell-based studies to elucidate the mechanisms underlying epigenetic reprogramming or other pathways for generational inheritance; studies of the combined effects of stress or heat exposure with specific toxicants or mixtures of toxicants or deployment-related mixtures; and studies using surrogate tissues such as blood, saliva, urine, or sperm to inform the exposures, mechanisms, and outcomes in target tissues and organs. Research efforts in this area should coordinate with and be informed by ongoing studies being conducted by the TaRGET consortium and the other consortia working on mapping the human epigenome.
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, although reproductive or multigenerational studies using surrogate exposures may be adequate if they sufficiently address the research needs identified in this report. The knowledge gaps related to the adverse reproductive effects in veterans and developmental effects in offspring of these exposures include the following: • Windows of susceptibility It is understood that exposures across the lifecourse have the potential to cause adverse health effects in exposed individuals.
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. What effects occur in parental germ cells, what happens after the exposure ceases, and whether and how lifecourse events compound epigenetic alterations are some of the knowledge gaps related to the nature of these alterations, as discussed below.
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. INTER- AND TRANSGENERATIONAL HEALTH EFFECTS As summarized in Chapter 8, the reproductive and developmental health outcomes that may be associated with parental deployment exposures include the following: • behavioral and neurological dysfunction in offspring associated with maternal exposure to organophosphate pesticides;
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The typical generational animal studies required by regulatory agencies to protect human health expose animals to a toxicant throughout the entire study period, and each generation is exposed. These studies are not particularly helpful for trying to determine the types of generational effects that might manifest in offspring following parental exposure during deployment.
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From page 469... ...
In some cases it may be advantageous to conduct animal and mechanistic research rather than epidemiologic studies or a health monitoring program, given the ethical, time, and resource constraints inherent in human research. However, an expanded understanding of how deployment exposures can affect the health of veteran's children or other descendants will require an integrated approach informed by health monitoring, epidemiological studies, and basic research.
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Environmental Research 158:737–747. IHEC (International Human Epigenome Consortium)
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