Activation of Inflammation/NF-κB Signaling in Infants Born to Arsenic-Exposed Mothers

Rebecca C Fry,J Peter Svensson,Chulabhorn Mahidol,Sumitra Soontararuks,Sumontha Nookabkaew,Chandni Valiathan,Bradley J Hogan,Leona D Samson,Mathuros Ruchirawat,Manlin Luo,Sanchita Bhattacharya,Panida Navasumrit,Krittinee Kandjanapa,Vivian G Cheung

doi:10.1371/journal.pgen.0030207

Abstract

The long-term health outcome of prenatal exposure to arsenic has been associated with increased mortality in human populations. In this study, the extent to which maternal arsenic exposure impacts gene expression in the newborn was addressed. We monitored gene expression profiles in a population of newborns whose mothers experienced varying levels of arsenic exposure during pregnancy. Through the application of machine learning–based two-class prediction algorithms, we identified expression signatures from babies born to arsenic-unexposed and -exposed mothers that were highly predictive of prenatal arsenic exposure in a subsequent test population. Furthermore, 11 transcripts were identified that captured the maximal predictive capacity to classify prenatal arsenic exposure. Network analysis of the arsenic-modulated transcripts identified the activation of extensive molecular networks that are indicative of stress, inflammation, metal exposure, and apoptosis in the newborn. Exposure to arsenic is an important health hazard both in the United States and around the world, and is associated with increased risk for several types of cancer and other chronic diseases. These studies clearly demonstrate the robust impact of a mother's arsenic consumption on fetal gene expression as evidenced by transcript levels in newborn cord blood.

Highlights

Arsenic is a ubiquitous environmental pollutant and a known human carcinogen [1]
Chronic arsenic exposure is an important public health hazard around the world, with millions of people exposed to drinking water with levels far exceeding the guideline of 10 lg/l established by the World Health Organization (WHO)
Using a population of arsenic-exposed and -unexposed mothers, we set out to identify gene expression changes in the cord blood of newborns significantly associated with the extent of prenatal arsenic exposure

Summary

Introduction

Chronic arsenic exposure is an important public health hazard around the world, with millions of people exposed to drinking water with levels far exceeding the guideline of 10 lg/l established by the WHO. Exposure to arsenic-contaminated drinking water is alarmingly high in many countries, most notably Bangladesh, where .25 million people are chronically exposed to extreme arsenic levels. Arsenic contamination is a significant health concern in the United States, with numerous public water supplies measuring above the WHO limit [2]. Epidemiological studies indicate that chronic arsenic exposure in drinking water is associated with increased risk of skin, bladder, lung, liver, and kidney cancer [1]; in 1987, arsenic was classified as a Group 1 carcinogen by the International Agency for Research on Cancer. Arsenic is implicated in other human diseases such as vascular disorders, peripheral neuropathy, bronchiecstasis, and diabetes [1]

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