Activation of inflammation/NF-kappaB signaling in infants born to arsenic-exposed mothers.
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.
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
Rebecca C
RC
Fry
Panida
P
Navasumrit
Chandni
C
Valiathan
J Peter
JP
Svensson
Bradley J
BJ
Hogan
Manlin
M
Luo
Sanchita
S
Bhattacharya
Krittinee
K
Kandjanapa
Sumitra
S
Soontararuks
Sumontha
S
Nookabkaew
Chulabhorn
C
Mahidol
Mathuros
M
Ruchirawat
Leona D
LD
Samson
D000328:Adult; D000818:Animals; D020261:Arsenic Poisoning / Q000235:genetics*; D001665:Binding Sites; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D005819:Genetic Markers; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D007249:Inflammation / Q000235:genetics*; D018811:Maternal Exposure; D051379:Mice; D016328:NF-kappa B / Q000235:genetics*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics*; D015398:Signal Transduction; D013045:Species Specificity; D013785:Thailand; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
D005819:Genetic Markers; D016328:NF-kappa B; D014157:Transcription Factors