title: Perchlorate disrupts embryonic androgen synthesis and reproductive development in threespine stickleback without changing whole-body levels of thyroid hormone.
abstract: Perchlorate, an environmental contaminant, disrupts normal functioning of the thyroid. We previously showed that perchlorate disrupts behavior and gonad development, and induces external morphological changes in a vertebrate model organism, the threespine stickleback. Whether perchlorate alters these phenotypes via a thyroid-mediated mechanism, and the extent to which the effects depend on dose, are unknown. To address these questions, we chronically exposed stickleback to control conditions and to three concentrations of perchlorate (10, 30 and 100ppm) at various developmental stages from fertilization to reproductive maturity. Adults chronically exposed to perchlorate had increased numbers of thyroid follicles and decreased numbers of thyrocytes. Surprisingly, T4 and T3 levels in larval, juvenile, and adult whole fish chronically exposed to perchlorate did not differ from controls, except at the lowest perchlorate dose, suggesting a non-monotonic dose response curve. We found no detectable abnormalities in external phenotype at any dose of perchlorate, indicating that the increased number of thyroid follicles compensated for the disruptive effects of these doses. In contrast to external morphology, gonadal development was altered substantially, with the highest dose of perchlorate causing the largest effects. Perchlorate increased the number both of early stage ovarian follicles in females and of advanced spermatogenic stages in males. Perchlorate also disrupted embryonic androgen levels. We conclude that chronic perchlorate exposure may not result in lasting adult gross morphological changes but can produce lasting modifications to gonads when compensation of T3 and T4 levels occurs by thyroid follicle hyperplasia. Perchlorate may therefore affect vertebrate development via both thyroidal and non-thyroidal mechanisms.
authors.affiliation: Institute of Ecology and Evolution, Department of Biology, University of Oregon, Eugene, OR 97403, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Petersen
authors.affiliation: Department of Biological Sciences, University of Alaska Anchorage, Anchorage, AK 99508, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Dillon
authors.affiliation: Department of Biological Sciences, University of Alaska Anchorage, Anchorage, AK 99508, USA.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Bernhardt
authors.affiliation: Institute of Ecology and Evolution, Department of Biology, University of Oregon, Eugene, OR 97403, USA.
authors.forename: Roberta
authors.initials: R
authors.lastname: Torunsky
authors.affiliation: Institute of Neuroscience, Department of Biology, University of Oregon, Eugene, OR 97403, USA.
authors.forename: John H
authors.initials: JH
authors.lastname: Postlethwait
authors.affiliation: Department of Biological Sciences, University of Alaska Anchorage, Anchorage, AK 99508, USA.
authors.forename: Frank A
authors.initials: FA
authors.lastname: von Hippel
authors.affiliation: Department of Biological Sciences, University of Alaska Anchorage, Anchorage, AK 99508, USA.
authors.forename: C
authors.initials: C
authors.lastname: Loren Buck
authors.affiliation: Institute of Ecology and Evolution, Department of Biology, University of Oregon, Eugene, OR 97403, USA. Electronic address: wcresko@uoregon.edu.
authors.forename: William A
authors.initials: WA
authors.lastname: Cresko
mesh_terms: D000728:Androgens / Q000096:biosynthesis*; D000818:Animals; D004625:Embryo, Nonmammalian / Q000187:drug effects; D005260:Female; D006066:Gonads / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D006801:Humans; D008297:Male; D010472:Perchlorates / Q000633:toxicity*; D012098:Reproduction / Q000187:drug effects*; D012733:Sex Differentiation / Q000187:drug effects*; D023701:Smegmamorpha / Q000097:blood / Q000196:embryology*; D013961:Thyroid Gland / Q000187:drug effects* / Q000473:pathology; D013963:Thyroid Hormones / Q000097:blood / Q000378:metabolism*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D000728:Androgens; D010472:Perchlorates; D013963:Thyroid Hormones; D014874:Water Pollutants, Chemical; C494474:perchlorate
keywords: 11-Ketotestosterone; Dose response curve embryonic androgen levels; Endocrine disruption; Gasterosteus aculeatus; Steroid biogenesis