Effects of Low-Dose Drinking Water Arsenic on Mouse Fetal and Postnatal Growth and Development

Abstract

BackgroundArsenic (As) exposure is a significant worldwide environmental health concern. Chronic exposure via contaminated drinking water has been associated with an increased incidence of a number of diseases, including reproductive and developmental effects. The goal of this study was to identify adverse outcomes in a mouse model of early life exposure to low-dose drinking water As (10 ppb, current U.S. EPA Maximum Contaminant Level).Methodology and FindingsC57B6/J pups were exposed to 10 ppb As, via the dam in her drinking water, either in utero and/or during the postnatal period. Birth outcomes, the growth of the F1 offspring, and health of the dams were assessed by a variety of measurements. Birth outcomes including litter weight, number of pups, and gestational length were unaffected. However, exposure during the in utero and postnatal period resulted in significant growth deficits in the offspring after birth, which was principally a result of decreased nutrients in the dam's breast milk. Cross-fostering of the pups reversed the growth deficit. Arsenic exposed dams displayed altered liver and breast milk triglyceride levels and serum profiles during pregnancy and lactation. The growth deficits in the F1 offspring resolved following separation from the dam and cessation of exposure in male mice, but did not resolve in female mice up to six weeks of age.Conclusions/SignificanceExposure to As at the current U.S. drinking water standard during critical windows of development induces a number of adverse health outcomes for both the dam and offspring. Such effects may contribute to the increased disease risks observed in human populations.

Fetal exposure to arsenic results in hyperglycemia, hypercholesterolemia, and nonalcoholic fatty liver disease in adult mice

“…Importantly, NAFLD is estimated to be prevalent in 20-30% of the general population in western countries [56], so understanding the underlying causes for the onset and progression of this disease is essential. In this regard, our results are consistent with previous studies showing that arsenic exposure leads to fatty livers in pregnant female mice [8]. Thus, arsenic may be an important toxicant with particular sensitivity to the developing fetus, predisposing mice to NAFLD.…”

“…An interesting observation was that the female mice exposed to arsenic IU were significantly underweight during the first two weeks after birth, when compared to their control counterparts. Similarly, Kozul-Horvath et al, showed that female mice that were exposed to 10 ppb arsenic IU, had a delay in weight gain at postnatal day 21 [8]. Our IU arsenicexposed mice showed a full recovery in weight by 4 weeks of age, and no significant changes were observed thereafter.…”

“…Affected countries include Bangladesh, with over 30 million people exposed to concentrations between 0.1 µg/L and 864 µg/L, India, with 40 million people exposed to concentrations exceeding 1000 µg/L, as well as China (1.5 million people) and the United States (2.5 million people) exposed to concentrations between 1 µg/L and 100 µg/L of arsenic in the drinking water [2][3][4][5]. Importantly, exposure to arsenic has been associated with an array of diseases ranging from multiple forms of cancer, to developmental and reproductive effects, as well as cardiovascular and metabolic disorders [6][7][8][9].…”

Permeation of roxarsone and its metabolites increases caco-2 cell proliferation

“…Other investigators have confirmed that micromolar levels of iAs caused DNA damage, cell arrest, and probable reduction of levels of cyclin/CDKs [37,38]. iAs at micromolar levels have public health outcomes in occurrence of cancers and metabolic diseases, endocrine disruption, and altered immune response [39-44]. …”

A transcriptomics study on hepatic lipid metabolism in mice exposed to contaminated drinking water

“…Recently, drinking water safety has received great concern, since growing evidence indicates that long-term exposure to contaminated drinking water can induce carcinogenicity (Keshavarzi et al 2012), genotoxicity (Rebola et al 2011), and developmental (Kozul-Horvath et al 2012) and reproductive toxicities (Welsch et al 2008). Yangtze River is the longest river in China, and the river basin supports one-third of China's population and contributes about 40 % of the national gross domestic product of China ).…”