Transcriptional analysis of endocrine disruption using zebrafish and massively parallel sequencing.
Endocrine-disrupting chemicals (EDCs), including plasticizers, pesticides, detergents, and pharmaceuticals, affect a variety of hormone-regulated physiological pathways in humans and wildlife. Many EDCs are lipophilic molecules and bind to hydrophobic pockets in steroid receptors, such as the estrogen receptor and androgen receptor, which are important in vertebrate reproduction and development. Indeed, health effects attributed to EDCs include reproductive dysfunction (e.g. reduced fertility, reproductive tract abnormalities, and skewed male:female sex ratios in fish), early puberty, various cancers, and obesity. A major concern is the effects of exposure to low concentrations of endocrine disruptors in utero and post partum, which may increase the incidence of cancer and diabetes in adults. EDCs affect transcription of hundreds and even thousands of genes, which has created the need for new tools to monitor the global effects of EDCs. The emergence of massive parallel sequencing for investigating gene transcription provides a sensitive tool for monitoring the effects of EDCs on humans and other vertebrates, as well as elucidating the mechanism of action of EDCs. Zebrafish conserve many developmental pathways found in humans, which makes zebrafish a valuable model system for studying EDCs, especially on early organ development because their embryos are translucent. In this article, we review recent advances in massive parallel sequencing approaches with a focus on zebrafish. We make the case that zebrafish exposed to EDCs at different stages of development can provide important insights on EDC effects on human health.
Department of MedicineUniversity of California San Diego, 9500 Gilman Drive 0605, La Jolla, California 92093-0605, USACSRC and BIMRCSan Diego State University, 5500 Campanile Drive, San Diego, California 92182-7720, USADepartment of MedicineMedical University of South Carolina, 135 Cannon Street, Suite 303 MSC 835, Charleston, South Carolina 29425, USA mebaker@ucsd.edu hardiman@musc.edu.
Michael E
ME
Baker
Department of MedicineUniversity of California San Diego, 9500 Gilman Drive 0605, La Jolla, California 92093-0605, USACSRC and BIMRCSan Diego State University, 5500 Campanile Drive, San Diego, California 92182-7720, USADepartment of MedicineMedical University of South Carolina, 135 Cannon Street, Suite 303 MSC 835, Charleston, South Carolina 29425, USADepartment of MedicineUniversity of California San Diego, 9500 Gilman Drive 0605, La Jolla, California 92093-0605, USACSRC and BIMRCSan Diego State University, 5500 Campanile Drive, San Diego, California 92182-7720, USADepartment of MedicineMedical University of South Carolina, 135 Cannon Street, Suite 303 MSC 835, Charleston, South Carolina 29425, USA mebaker@ucsd.edu hardiman@musc.edu.
Gary
G
Hardiman
D000818:Animals; D001483:Base Sequence; D003920:Diabetes Mellitus / Q000139:chemically induced; D052244:Endocrine Disruptors / Q000633:toxicity*; D004781:Environmental Exposure; D005260:Female; D059014:High-Throughput Nucleotide Sequencing; D008431:Maternal-Fetal Exchange; D023421:Models, Animal; D009369:Neoplasms / Q000139:chemically induced; D011247:Pregnancy; D012098:Reproduction / Q000187:drug effects; D017422:Sequence Analysis, DNA; D059467:Transcriptome / Q000235:genetics; D015027:Zebrafish
D052244:Endocrine Disruptors
endocrine disruptors; massive parallel sequencing; steroid receptors; zebrafish