Impact of prenatal arsenic exposure on chronic adult diseases

Exposure to environmental stressors during susceptible windows of development can result in negative health outcomes later in life, a concept known as the Developmental Origins of Health and Disease (DOHaD). There is a growing body of evidence that exposures to metals early in life (in utero and postnatal) increase the risk of developing adult diseases such as cancer, cardiovascular disease, non-alcoholic fatty liver disease, and diabetes. Of particular concern is exposure to the metalloid arsenic, a drinking water contaminant and worldwide health concern. Epidemiological studies of areas with high levels of arsenic in the drinking water, such as some regions in Chile and Bangladesh, indicate an association between in utero arsenic exposure and the development of adult diseases. Therefore, the need for experimental models to address the mechanism underlining early onset of adult diseases have emerged including the in utero and whole-life exposure models. This review will highlight the epidemiological events and subsequent novel experimental models implemented to study the impact of early life exposure to arsenic on the development of adult diseases. In addition, current research using these models will be discussed as well as possible underlying mechanism for the early onset of disease. Abbreviations: ALT: alanine aminotransferase; AMI: acute myocardial infarction; AST: aspartate aminotransferase; ATSDR: Agency for Toxic Substances and Disease Registry; CVD: cardiovascular disease; DMA: dimethylarsinate; DOHaD: Developmental Origins of Health and Disease; EPA: U.S. Environmental Protection Agency; ER-α: estrogen receptor alpha; HDL: high-density lipoprotein; HOMA-IR: homeostatic model assessment of insulin resistance; iAs: inorganic arsenic; LDL: low-density lipoprotein; MetS: metabolic syndrome; MMA: monomethylarsonate; NAFLD: non-alcoholic fatty liver disease; PND: postnatal day; ppb: parts per billion; ppm: parts per million; SAM: S-adenosylmethionine; USFDA: United States Food and Drug Administration.