TY - JOUR
T1 - Perchlorate disrupts embryonic androgen synthesis and reproductive development in threespine stickleback without changing whole-body levels of thyroid hormone
AU - Petersen, Ann M.
AU - Dillon, Danielle
AU - Bernhardt, Richard A.
AU - Torunsky, Roberta
AU - Postlethwait, John H.
AU - von Hippel, Frank A.
AU - Loren Buck, C.
AU - Cresko, William A.
N1 - Funding Information:
We thank Poh Kheng Loi for expertise in histology preparations, and Ruth Bremiller, Yi-Lin Yan, Christoff G. Furin, and John Baker for helpful discussion and technical expertise. We also thank Dr. K.-Y. Francis Pau of the Endocrine Technology & Support Lab at Oregon National Primate Research Center Oregon Health & Science for invaluable help with hormone analysis. Funding was provided by NIH Grant number 1RO1ES017039-01A1 . Fish were collected under Alaska Department of Fish and Game permit SF-2010-029 and SF-2011-025 , and all research protocols were approved by the UAA Institutional Animal Care and Use Committee (IRB reference # 159870-1 ) and the University of Oregon Animal Care and Use Committee (protocol #10-16R ).
Publisher Copyright:
© 2014 Elsevier Inc.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.
AB - 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.
KW - 11-Ketotestosterone
KW - Dose response curve embryonic androgen levels
KW - Endocrine disruption
KW - Gasterosteus aculeatus
KW - Steroid biogenesis
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U2 - 10.1016/j.ygcen.2014.10.015
DO - 10.1016/j.ygcen.2014.10.015
M3 - Article
C2 - 25448260
AN - SCOPUS:84911376575
SN - 0016-6480
VL - 210
SP - 130
EP - 144
JO - General and comparative endocrinology
JF - General and comparative endocrinology
ER -