Molecular targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) within the zebrafish ovary: insights into TCDD-induced endocrine disruption and reproductive toxicity.
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.
Heiden
Tisha C King
TC
Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI, USA.
Struble
Craig A
CA
Rise
Matthew L
ML
Hessner
Martin J
MJ
Hutz
Reinhold J
RJ
Carvan
Michael J
MJ
D000818:Animals; D052244:Endocrine Disruptors / Q000633:toxicity*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D006062:Gonadotropins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D006080:Ovarian Follicle / Q000187:drug effects / Q000378:metabolism; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D012045:Regulatory Sequences, Nucleic Acid / Q000187:drug effects; D012098:Reproduction / Q000187:drug effects* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D015027:Zebrafish
D052244:Endocrine Disruptors; D004967:Estrogens; D006062:Gonadotropins; D000072317:Polychlorinated Dibenzodioxins