Putative adverse outcome pathway development based on physiological responses of female fathead minnows to model estrogen versus androgen receptor agonists.

Autor: Morshead ML; Oak Ridge Institute for Science and Education, US EPA, Great Lakes Toxicology and Ecology Division, Duluth, MN, USA., Jensen KM; US EPA, Great Lakes Toxicology and Ecology Division, Duluth, MN, USA., Ankley GT; US EPA, Great Lakes Toxicology and Ecology Division, Duluth, MN, USA., Vliet S; US EPA, Scientific Computing and Data Curation Division, Duluth, MN, USA., LaLone CA; US EPA, Great Lakes Toxicology and Ecology Division, Duluth, MN, USA., Aller AV; Arizona State University, School of Mathematical and Natural Sciences, Phoenix, AZ, USA., Watanabe KH; Arizona State University, School of Mathematical and Natural Sciences, Phoenix, AZ, USA., Villeneuve DL; US EPA, Great Lakes Toxicology and Ecology Division, Duluth, MN, USA. Electronic address: villeneuve.dan@epa.gov.
Jazyk: angličtina
Zdroj: Aquatic toxicology (Amsterdam, Netherlands) [Aquat Toxicol] 2023 Aug; Vol. 261, pp. 106607. Date of Electronic Publication: 2023 Jun 09.
DOI: 10.1016/j.aquatox.2023.106607
Abstrakt: Several adverse outcome pathways (AOPs) have linked molecular initiating events like aromatase inhibition, androgen receptor (AR) agonism, and estrogen receptor (ER) antagonism to reproductive impairment in adult fish. Estrogen receptor agonists can also cause adverse reproductive effects, however, the early key events (KEs) in an AOP leading to this are mostly unknown. The primary aim of this study was to develop hypotheses regarding the potential mechanisms through which exposure to ER agonists might lead to reproductive impairment in female fish. Mature fathead minnows were exposed to 1 or 10 ng 17α-ethynylestradiol (EE2)/L or 10 or 100 µg bisphenol A (BPA)/L for 14 d. The response to EE2 and BPA was contrasted with the effects of 500 ng/L of 17β-trenbolone (TRB), an AR agonist, as well as TRB combined with the low and high concentrations of EE2 or BPA tested individually. Exposure to 10 ng EE2/L, 100 µg BPA/L, TRB, or the various mixtures with TRB caused significant decreases in plasma concentrations of 17β-estradiol. Exposure to TRB alone caused a significant reduction in plasma vitellogenin (VTG), but VTG was unaffected or even increased in females exposed to EE2 or BPA alone or, in most cases, in mixtures with TRB. Over the course of the 14-d exposure, the only treatments that clearly did not affect egg production were 1 ng EE2/L and 10 µg BPA/L. Based on these results and knowledge of hypothalamic-pituitary-gonadal axis function, we hypothesize an AOP whereby decreased production of maturation-inducing steroid leading to impaired oocyte maturation and ovulation, possibly due to negative feedback or direct inhibitory effects of membrane ER activation, could be responsible for causing adverse reproductive impacts in female fish exposed to ER agonists.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Published by Elsevier B.V.)
Databáze: MEDLINE
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