Molecular targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) within the zebrafish ovary: insights into TCDD-induced endocrine disruption and reproductive toxicity. Reprod Toxicol 2008 Jan;25(1):47-57
Date
09/22/2007Pubmed ID
17884332Pubmed Central ID
PMC2693207DOI
10.1016/j.reprotox.2007.07.013Scopus ID
2-s2.0-37349056732 (requires institutional sign-in at Scopus site) 55 CitationsAbstract
TCDD is a reproductive toxicant and endocrine disruptor, yet the mechanisms by which it causes these reproductive alterations are not fully understood. In order to provide additional insight into the molecular mechanisms that underlie TCDD's reproductive toxicity, we assessed TCDD-induced transcriptional changes in the ovary as they relate to previously described impacts on serum estradiol concentrations and altered follicular development in zebrafish. In silico computational approaches were used to correlate candidate regulatory motifs with observed changes in gene expression. Our data suggest that TCDD inhibits follicle maturation via attenuated gonadotropin responsiveness and/or depressed estradiol biosynthesis, and that interference of estrogen-regulated signal transduction may also contribute to TCDD's impacts on follicular development. TCDD may also alter ovarian function by disrupting various signaling pathways such as glucose and lipid metabolism, and regulation of transcription. Furthermore, events downstream from initial TCDD molecular-targets likely contribute to ovarian toxicity following chronic exposure to TCDD. Data presented here provide further insight into the mechanisms by which TCDD disrupts follicular development and reproduction in fish, and can be used to formulate new hypotheses regarding previously documented ovarian toxicity.
Author List
Heiden TC, Struble CA, Rise ML, Hessner MJ, Hutz RJ, Carvan MJ 3rdAuthors
Martin J. Hessner PhD Professor in the Pediatrics department at Medical College of WisconsinReinhold J. Hutz in the Biological Sciences department at University of Wisconsin - Milwaukee
MESH terms used to index this publication - Major topics in bold
AnimalsEndocrine Disruptors
Estrogens
Female
Gene Expression Profiling
Gene Expression Regulation, Developmental
Gonadotropins
Oligonucleotide Array Sequence Analysis
Ovarian Follicle
Ovary
Polychlorinated Dibenzodioxins
Regulatory Sequences, Nucleic Acid
Reproduction
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Transcription, Genetic
Zebrafish