Effects of environmental steroid mixtures are regulated by individual steroid receptor signaling

Schmid, Simon; Willi, Raffael Alois; Fent, Karl

doi:10.1016/j.aquatox.2020.105562

Cited by 7 publications

(3 citation statements)

References 41 publications

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“…In this study, the observed differences in endocrine gene interference across various developmental stages could be attributed to the undeveloped gonads of zebrafish in the initial two stages, where the involved enzymes or receptors are similar. However, in the juvenile fish stage, as their gonads begin to develop, the involved enzymes or receptors diverge from those in the earlier stages [ 34 ]. Consequently, Tet exposure may result in hormonal imbalances in zebrafish at different stages, leading to varying degrees of reproductive toxicity.…”

Section: Discussionmentioning

confidence: 99%

Enantioselective Toxicity of Tetramethrin to Different Developmental Stages of Zebrafish (Danio rerio)

Feng,

Xu,

Huang

et al. 2024

Toxics

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Chiral pesticides exhibit enantioselective differences in processes such as biological absorption, metabolism, and toxic effects. Organisms have different physiological characteristics at different developmental stages. Therefore, conducting enantiomeric toxicity studies at different developmental stages of organisms can help deepen the understanding of the ecological effects of chiral pesticides. This study focused on trans-tetramethrin (Tet) and investigated the enantioselectivity in bioconcentration, developmental toxicity, estrogenic effects, and immunotoxicity of Tet’s racemate ((±)-Tet) and its two enantiomers ((+)-Tet and (−)-Tet) in three developmental stages of zebrafish: embryos, yolk sac larvae, and juveniles. The results showed that Tet exhibited different enantioselectivity in lethal, bioconcentration, and teratogenic effects on zebrafish at different developmental stages. The LC50 value was (+)-Tet > (±)-Tet > (−)-Tet, with embryos being the most sensitive, followed by juveniles and yolk sac larvae. The enantioselective bioconcentration was (±)-Tet > (+)-Tet > (−)-Tet, and the bioconcentration effect was greater in embryos than that in yolk sac larvae and juveniles. Developmental toxicity indicated that (+)-Tet and (±)-Tet had higher teratogenic effects on yolk sac larvae than on embryos. Tet exhibited different enantioselective effects on the expression of zebrafish estrogen-related genes and innate immune-related genes at different developmental stages. These results will contribute to a more comprehensive assessment of the aquatic toxicity and environmental risks of chiral pesticides.

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Section: Discussionmentioning

confidence: 99%

Enantioselective Toxicity of Tetramethrin to Different Developmental Stages of Zebrafish (Danio rerio)

Feng,

Xu,

Huang

et al. 2024

Toxics

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“…Inhibition of 5AR reduced the DHT levels in tissues and can affect the androgen receptor (AR) expression [28][29][30]. Steroids such as androgens, estrogens and corticosteroids and inhibitors of 5AR are widely utilized in pharmacological applications, and these chemicals may act as EDCs and substantially impact fish and other species that are exposed to the environment [31,32]. We compared the 5AR activities and inhibition rates of 5AR by finasteride and dutasteride between human cell lines and fish cell lines.…”

Section: Discussionmentioning

confidence: 99%

Development of a Liquid Chromatography/Mass Spectrometry-Based Inhibition Assay for the Screening of Steroid 5-α Reductase in Human and Fish Cell Lines

et al. 2021

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Steroid 5-α reductase (5AR) is responsible for the reduction of steroids to 5-α reduced metabolites, such as the reduction of testosterone to 5-α dihydrotestosterone (DHT). A new adverse outcome pathway (AOP) for 5AR inhibition to reduce female reproduction in fish (AOP 289) is under development to clarify the antiestrogenic effects of 5AR inhibitors in female fish. A sensitive method for the DHT analysis using chemical derivatization and liquid chromatography–tandem mass spectrometry was developed. A cell-based 5AR inhibition assay that utilizes human cell lines, a transient overexpression system, and fish cell lines was developed. The measured IC50 values of two well-known 5AR inhibitors, finasteride and dutasteride, were comparable in the different systems. However, the IC50 of dutasteride in the fish cell lines was lower than that in the human cell lines. Finasteride showed a higher IC50 against the RTG-2 cell line. These results demonstrated that 5ARs inhibition could differ in terms of structural characteristics among species. The assay has high sensitivity and reproducibility and is suitable for the application in 5AR inhibition screening for various endocrine disruption chemicals (EDCs). Future studies will continue to evaluate the quantitative inhibition of 5AR by EDCs to compare the endocrine-disrupting pathway in different species.

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“…As it plays an important role in regulating hatching (Nesan et al, 2012), swimming activity (Castillo-Ramírez et al, 2019), circadian rhythm (Zhao et al, 2018), musculoskeletal development, growth and stress response (Apaydin et al, 2020), and exposure to exogenous glucocorticoids can be especially disruptive during early development. Relevant research reported prednisone induced decreased bone mineral density and bone loss (Schmid et al, 2020a;Schmid et al, 2020b). Furthermore, the long-term use of glucocorticoids will induce osteoporosis mediated by glucocorticoid receptor-dependent and -independent pathways (Zhao et al, 2016;Zhao et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Prediction and Verification of Epimedium Flavonoids With Different Glycosylation Numbers in Reversing Glucocorticoid-Induced Bone Formation Inhibition by Molecular Docking and Zebrafish

Jiang

Xiao

et al. 2022

Front. Environ. Sci.

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Glucocorticoids have been detected in environmental waters, and their biological potency has raised concerns on their impact on aquatic vertebrates especially fish. Numerous researches showed that the continuous and direct contact of aquatic vertebrates with glucocorticoid contaminants in environmental water will cause bone formation inhibition. The aim of this study is to predict and verify the effect of icaritin (IT), icariin (ICA), and baohuside-I (BHG-I) in reversing glucocorticoid-induced bone formation inhibition (GIBFI) by molecular docking and zebrafish model. We contrasted their activity in reversing GIBFI from their affinity to bone metabolism proteins (OPG, RANKL, BMP-2, BMP-4, Runx-2) by molecular docking. Subsequently, zebrafish model was adopted to evaluate their reverse effects on GIBFI. Alizarin red staining coupled with image quantification were performed to evaluate the effects of ICA, IT, and BHG-I on skeleton stained area (SSA) and cumulative optical density (COD). Inductively coupled plasma-mass spectrometry was applied to determine the contents of bone mineral elements (CBME, Mg, K, Ca, Fe, Zn) in zebrafish bones. Docking results showed the receptors (BMP-2, BMP-4, and Runx2) all combined well to ICA, while BHG-I bound well to OPG, the affinity between IT and the above targets were the weakest. Fortunately, IT, ICA, and BHG-I significantly increased the SSA, COD, and the contents of Ca compared with the model group (p < 0.05) in the order of IT>ICA>BHG-I. In conclusion, the glycosyl groups increased the H-bond affinity between flavonoids and target sites, which weakened bone formation. IT, BHG-I, and ICA all alleviated GIBFI, but their intensity order was IT>ICA>BHG-I.

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Effects of environmental steroid mixtures are regulated by individual steroid receptor signaling

Cited by 7 publications

References 41 publications

Enantioselective Toxicity of Tetramethrin to Different Developmental Stages of Zebrafish (Danio rerio)

Enantioselective Toxicity of Tetramethrin to Different Developmental Stages of Zebrafish (Danio rerio)

Development of a Liquid Chromatography/Mass Spectrometry-Based Inhibition Assay for the Screening of Steroid 5-α Reductase in Human and Fish Cell Lines

Prediction and Verification of Epimedium Flavonoids With Different Glycosylation Numbers in Reversing Glucocorticoid-Induced Bone Formation Inhibition by Molecular Docking and Zebrafish

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