Gene expression profiling in rat cerebellum following in utero and lactational exposure to mixtures of methylmercury, polychlorinated biphenyls and organochlorine pesticides.
Although human populations are continuously exposed to complex mixtures of contaminants, the effects of such exposure on the developing brain transcriptome are poorly characterized. Rats were exposed perinatally to the northern contaminant mixture (NCM) which was designed to reflect the blood contaminant profile of Canadian arctic populations, to components of the NCM administered separately (methylmercury (MeHg), polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCs)) or to the goitrogen propylthiouracyl. Post-natal day (PND) 14 cerebellum global gene expression resulting from such exposures was investigated using high-density cDNA microarrays. Fifty known genes were identified as differentially expressed between the control group and at least one other treatment group. The microarray data were validated by quantitative PCR (qPCR) on a subset of 10 genes. The differentially expressed genes are involved in a variety of processes, including nerve cell differentiation, migration, myelination and synaptic transmission. The comparison of cerebellum gene expression profiles resulting from exposure to the NCM and its individual components in male and female pups revealed that (i) gender is a crucial biological variable influencing genomic response to environmental contaminants and (ii) contaminant co-exposure significantly masks the effects of individual mixture components on cerebellum gene expression.
Padhi
B K
BK
Environment and Occupational Toxicology Division, HECSB, Health Canada, Tunney's Pasture, Ottawa, Ontario K1A 0L2, Canada.
Pelletier
G
G
Williams
A
A
Berndt-Weis
L
L
Yauk
C
C
Bowers
W J
WJ
Chu
I
I
D000818:Animals; D000831:Animals, Newborn; D002135:Calcium-Binding Proteins / Q000235:genetics; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D016000:Cluster Analysis; D004785:Environmental Pollutants / Q000737:chemistry / Q000633:toxicity*; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D006843:Hydrocarbons, Chlorinated / Q000737:chemistry / Q000633:toxicity; D007774:Lactation; D008297:Male; D018811:Maternal Exposure; D008767:Methylmercury Compounds / Q000737:chemistry / Q000633:toxicity; D009479:Neuropeptides / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D010575:Pesticides / Q000737:chemistry / Q000145:classification / Q000633:toxicity*; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000633:toxicity; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012269:Ribosomal Proteins / Q000235:genetics; D012737:Sex Factors
D002135:Calcium-Binding Proteins; D004785:Environmental Pollutants; D016326:Extracellular Matrix Proteins; D020662:Guanine Nucleotide Exchange Factors; D006843:Hydrocarbons, Chlorinated; D008767:Methylmercury Compounds; D009479:Neuropeptides; C104971:Pcp2 protein, mouse; D010575:Pesticides; D012269:Ribosomal Proteins; C503128:Sparcl1 protein, rat; C060232:ribosomal protein L21; D011078:Polychlorinated Biphenyls