TY - JOUR
T1 - Estrogenic effects following larval exposure to the putative anti-estrogen, fulvestrant, in the fathead minnow (Pimephales promelas)
AU - Ali, Jonathan M.
AU - Palandri, Michael T.
AU - Kallenbach, Alex T.
AU - Chavez, Edwin
AU - Ramirez, Jonathan
AU - Onanong, Sathaporn
AU - Snow, Daniel D.
AU - Kolok, Alan S.
N1 - Funding Information:
This project and Jonathan Ali were partially supported by the Robert G. Daugherty Water for Food Global Institute's Graduate Assistantship Program, University of Nebraska. Luke Allmon, Kendall Schwarz, Del D'Souza and Katie Higgins provided technical assistance for this project. The authors also thank the laboratory of Heiko Schoenfuss, Ph.D., at St. Cloud State University for the histology training. The use of specific reagents or brand names does not constitute an endorsement of these products by the authors.
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2018/1
Y1 - 2018/1
N2 - The objective of the present study was to investigate the consequences of early-life exposure to fulvestrant on estrogenic gene expression in fathead minnow larvae. To address this objective, fathead minnow larvae were exposed to fulvestrant (ICI 182,780) during the window of sexual differentiation between 0 to 30 days post-hatch (dph). The four treatment groups in this study included: filtered water controls (never exposed), solvent controls (ethanol 0.01%), and nominally low (0.10 μg/L) and high (10.0 μg/L) doses of fulvestrant. Following 30 d exposure to their respective treatment, larvae were transferred to filtered water aquaria and assessed for alterations in endocrine-responsive gene expression (i.e., RT-qPCR), body size and survival. The remaining fish depurated in filtered water until reaching sexual maturity (180 dph) for assessment of persistent effects on sex characteristics, reproductive performance and sex ratio. Following the 30-d early life exposure, larvae showed upregulations of the endocrine-responsive genes ar, erβ and vtg in response to both low and high doses of fulvestrant, but showed no differences in survival or body mass. Upon reaching sexual maturity under depuration conditions, male minnows previously exposed to fulvestrant as larvae showed reductions in gonad mass along with the feminization of secondary sex characteristics with no observed effects in females. Exposure to fulvestrant had no effects on gonadal histology, reproductive performance or final sex ratio as adults. Results from this study demonstrate that aqueous exposure to fulvestrant is estrogenic in fathead minnow larvae and is capable of feminizing male fish as adults following early life exposure.
AB - The objective of the present study was to investigate the consequences of early-life exposure to fulvestrant on estrogenic gene expression in fathead minnow larvae. To address this objective, fathead minnow larvae were exposed to fulvestrant (ICI 182,780) during the window of sexual differentiation between 0 to 30 days post-hatch (dph). The four treatment groups in this study included: filtered water controls (never exposed), solvent controls (ethanol 0.01%), and nominally low (0.10 μg/L) and high (10.0 μg/L) doses of fulvestrant. Following 30 d exposure to their respective treatment, larvae were transferred to filtered water aquaria and assessed for alterations in endocrine-responsive gene expression (i.e., RT-qPCR), body size and survival. The remaining fish depurated in filtered water until reaching sexual maturity (180 dph) for assessment of persistent effects on sex characteristics, reproductive performance and sex ratio. Following the 30-d early life exposure, larvae showed upregulations of the endocrine-responsive genes ar, erβ and vtg in response to both low and high doses of fulvestrant, but showed no differences in survival or body mass. Upon reaching sexual maturity under depuration conditions, male minnows previously exposed to fulvestrant as larvae showed reductions in gonad mass along with the feminization of secondary sex characteristics with no observed effects in females. Exposure to fulvestrant had no effects on gonadal histology, reproductive performance or final sex ratio as adults. Results from this study demonstrate that aqueous exposure to fulvestrant is estrogenic in fathead minnow larvae and is capable of feminizing male fish as adults following early life exposure.
KW - Endocrine disruption
KW - Estrogenic effects
KW - Fulvestrant
KW - Gene expression
KW - Larval exposure
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UR - http://www.scopus.com/inward/citedby.url?scp=85034091952&partnerID=8YFLogxK
U2 - 10.1016/j.cbpc.2017.10.013
DO - 10.1016/j.cbpc.2017.10.013
M3 - Article
C2 - 29122702
AN - SCOPUS:85034091952
SN - 1532-0456
VL - 204
SP - 26
EP - 35
JO - Comparative Biochemistry and Physiology Part - C: Toxicology and Pharmacology
JF - Comparative Biochemistry and Physiology Part - C: Toxicology and Pharmacology
ER -