title: Sex-specific patterns and deregulation of endocrine pathways in the gene expression profiles of Bangladeshi adults exposed to arsenic contaminated drinking water.
abstract: Arsenic contamination of drinking water occurs globally and is associated with numerous diseases including skin, lung and bladder cancers, and cardiovascular disease. Recent research indicates that arsenic may be an endocrine disruptor. This study was conducted to evaluate the nature of gene expression changes among males and females exposed to arsenic contaminated water in Bangladesh at high and low doses. Twenty-nine (55% male) Bangladeshi adults with water arsenic exposure ranging from 50 to 1000 μg/L were selected from the Folic Acid Creatinine Trial. RNA was extracted from peripheral blood mononuclear cells for gene expression profiling using Affymetrix 1.0 ST arrays. Differentially expressed genes were assessed between high and low exposure groups for males and females separately and findings were validated using quantitative real-time PCR. There were 534 and 645 differentially expressed genes (p<0.05) in the peripheral blood mononuclear cells of males and females, respectively, when high and low water arsenic exposure groups were compared. Only 43 genes overlapped between the two sexes, with 29 changing in opposite directions. Despite the difference in gene sets both males and females exhibited common biological changes including deregulation of 17β-hydroxysteroid dehydrogenase enzymes, deregulation of genes downstream of Sp1 (specificity protein 1) transcription factor, and prediction of estrogen receptor alpha as a key hub in cardiovascular networks. Arsenic-exposed adults exhibit sex-specific gene expression profiles that implicate involvement of the endocrine system. Due to arsenic's possible role as an endocrine disruptor, exposure thresholds for arsenic may require different parameters for males and females.
authors.affiliation: New York University School of Medicine, Nelson Institute of Environmental Medicine, Tuxedo, NY, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Muñoz
authors.affiliation: New York University School of Medicine, Nelson Institute of Environmental Medicine, Tuxedo, NY, USA.
authors.forename: Yana
authors.initials: Y
authors.lastname: Chervona
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, USA.
authors.forename: Megan
authors.initials: M
authors.lastname: Hall
authors.affiliation: New York University School of Medicine, Nelson Institute of Environmental Medicine, Tuxedo, NY, USA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kluz
authors.affiliation: Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, USA. Electronic address: mvg7@columbia.edu.
authors.forename: Mary V
authors.initials: MV
authors.lastname: Gamble
authors.affiliation: New York University School of Medicine, Nelson Institute of Environmental Medicine, Tuxedo, NY, USA. Electronic address: Max.Costa@nyumc.org.
authors.forename: Max
authors.initials: M
authors.lastname: Costa
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000235:genetics; D000328:Adult; D020261:Arsenic Poisoning / Q000235:genetics*; D001152:Arsenicals / Q000009:adverse effects*; D001459:Bangladesh; D052244:Endocrine Disruptors / Q000633:toxicity*; D004781:Environmental Exposure / Q000009:adverse effects*; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D012737:Sex Factors; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D014881:Water Supply / Q000032:analysis*
chemical_list: D001152:Arsenicals; C506487:ESR1 protein, human; D052244:Endocrine Disruptors; D047628:Estrogen Receptor alpha; D005819:Genetic Markers; D014874:Water Pollutants, Chemical; D015067:17-Hydroxysteroid Dehydrogenases
keywords: Arsenic; Cardiovascular disease; HSD17B-1; Humans