The developmental basis of disease: Update on environmental exposures and animal models

Abstract

At the Prenatal Programming and Toxicity (PPTox) Conference I in 2008, I presented an overview of the developmental origins of health and disease field focusing on environmental chemical exposures and disease outcomes. At that time, I noted that the field was getting off the ground with a focus on developmental exposure to a small number of endocrine disrupting chemicals (EDCs) and disease outcomes across the lifespan in animal models. In this update, I note that the DOHaD field has changed significantly over the last decade. There are new windows of susceptibility including preconception, prepuberty, a focus on the mother and not just the offspring, and a significant focus on the new field of epigenetic transgenerational inheritance. New disease focus areas have sprung up including obesity, type 2 diabetes and fatty liver disease, all with a connection to developmental exposures to EDCs. There is also a focus on the study of new EDCs, molecular mechanisms, the development of new biomarkers of exposure and disease outcomes and studies focusing on intervention and prevention studies.

Timescales of developmental toxicity impacting on research and needs for intervention

“…The pre‐natal vulnerability to environmental toxicants has recently been highlighted . Thus, systematic reviews and meta‐analyses have related maternal exposure during pregnancy to air pollution and specific toxicants to indicators of impaired foetal growth, such as low birthweight or small for gestational age .…”

“…The pre-natal vulnerability to environmental toxicants has recently been highlighted. 19,20 Thus, systematic reviews and meta-analyses have related maternal exposure during pregnancy to air pollution and specific toxicants to indicators of impaired foetal growth, such as low birthweight or small for gestational age. [21][22][23] The increased developmental vulnerability to toxicants during development may involve all organ systems, but is probably most evident regarding the nervous system.…”

Development priority

“…The summary report emphasized the timescales, as developmental toxicity can result in lasting deficits and elevated risks of disease that may appear much later. Particularly worrisome are endocrine disruption effects, some of which may lead to transgenerational effects driven through epigenetic reprogramming of germ cells and stem cells. Air pollution is a global concern as an involuntary exposure, and exposures during early development appear to be particularly hazardous, though not yet recognized by regulatory agencies .…”

“…Although this nascent collaboration may still lead to better co‐ordination between academic and agency research, a remaining issue is the focus. Both government agencies and academic researchers continue to focus on the same chemical hazards that some time ago became recognized as priority pollutants, and about which much evidence has already accumulated . This critique has been raised in regard to scientific publications, and it also affects environmental monitoring that tends to prioritize the known hazards while ignoring emergent and yet‐unexplored environmental chemicals …”

“…Both government agencies and academic researchers continue to focus on the same chemical hazards that some time ago became recognized as priority pollutants, and about which much evidence has already accumulated. 4 This critique has been raised in regard to scientific publications, 10 and it also affects environmental monitoring that tends to prioritize the known hazards while ignoring emergent and yet-unexplored environmental chemicals. 11 The progress in research in this field has resulted in improved understanding of the pathways of environmental exposures that affect human beings during early development, the mechanisms of vulnerability, the role of epigenetic changes and stem cell toxicity, and the long-term adverse health consequences.…”