Refinement of an OECD test guideline for evaluating the effects of endocrine disrupting chemicals on aromatase gene expression and reproduction using novel transgenic cyp19a1a-eGFP zebrafish

Abstract

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A comparison of behavioral and reproductive parameters between wild-type, transgenic and mutant zebrafish: Could they all be considered the same “zebrafish” for reglementary assays on endocrine disruption?

“…This suggests that these transgenic/mutant models can be pertinently used in laboratory tests assessing the endocrine properties of chemicals such as the OECD TG 229 and TG 230 (OECD, 2009;, without compromising the basal expression of key endpoints. In that respect, the use of transgenic models instead of WT appears relevant as they provide additional information on the chemicals' mechanism of action on the tissuespecific expression of the transgene, as previously demonstrated (De Oliveira et al, 2020).…”

“…Circulating VTG concentrations were measured in whole blood by indirect competitive ELISA using a liquid handling robot Freedom EVO ® (Tecan, Switzerland) according to the protocol described in De Oliveira et al (2020). Briefly, whole blood samples were tested in 12 serial dilutions with a step of 3 (dilutions ranging from 1:500 to 1:88,573,500 for females and 1:100 to 1:17,714,700 for males).…”

“…Finally, during the last decades, due to the development of new genome editing technologies (Tol2 mediated transgenesis, bacterial artificial chromosome-based transgenesis, TALEs, CRISPR/Cas9…), a huge number of transgenic zebrafish models has emerged worldwide (Albadri et al 2017, Kawahara 2017. Several of these transgenic models have been efficiently used to study the effects of chemicals, especially endocrine disrupting chemicals (EDC), in aquatic organisms (Gorelick and Halpern 2011, Brion et al 2012, Gorelick et al 2014, Hinfray et al 2016, Hinfray et al 2018, De Oliveira et al 2020). Given the abovementioned differences reported between zebrafish strains, care should be taken before using transgenic models for assessing the effects of EDC.…”

The effect of conazoles on reproductive organs structure and function – a review

“…Several other widely used azol compounds (prochloraz and tebuconazole) lead to significant reduction of female egg numbers and oestradiol level in zebrafish. Additionally, tebuconazole reduced the expression of cyp19a, which correlated with the drop in oestradiol levels (Li et al 2019;De Oliveira et al 2020). The line of evidence suggests that several conazoles inhibit brain and ovarian aromatase activity in a dose-dependent manner, leading to disruption of oestrogen production (Hinfray et al 2006).…”

Estrogenic regulation of claudin 5 and tight junction protein 1 gene expression in zebrafish: A role on blood–brain barrier?

“…In mature female zebrafish, plasma E2 levels can vary from 3.5 × 10 −11 to 1.5 × 10 −8 M, depending on the assay used (De Oliveira et al., 2020; Manjunatha & Philip, 2016; Teng et al., 2020). Data are rare in mature males, and there is variability in E2 concentrations, probably due to the measurement method.…”