Effects of two Bisphenol A replacement compounds, 1,7-bis (4-hydroxyphenylthio)-3,5-dioxaheptane and Bisphenol AF, on development and mRNA expression in chicken embryos

Sharin, Tasnia; Gyasi, Helina; Williams, Kim L.; Crump, Doug; O’Brien, Jason M.

doi:10.1016/j.ecoenv.2021.112140

Cited by 3 publications

(2 citation statements)

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“…These gene targets are involved in maintaining bile acid homeostasis (Schumacher and Guo 2016 ) and bile duct development (Bernardo and Keri 2012 ). Such dysregulation is consistent with another study that found an increase in FGF19 expression in livers of chicken embryos exposed to DD-70 via egg injection (Sharin et al 2021b ). Overall, DD-70 and BPAF exposure may lead to disruption of bile acid and lipid regulation; however, further studies are warranted to evaluate this.…”

Section: Resultssupporting

confidence: 92%

Toxicity screening of bisphenol A replacement compounds: cytotoxicity and mRNA expression in LMH 3D spheroids

Sharin

Crump

O’Brien

2022

Environ Sci Pollut Res

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Previously, we showed that the chicken LMH cell line cultured as 3D spheroids may be a suitable animal free alternative to primary chicken embryonic hepatocytes (CEH) for avian in vitro chemical screening. In this study, cytotoxicity and mRNA expression were determined in LMH 3D spheroids following exposure to bisphenol A (BPA), five BPA replacement compounds (BPF, TGSH, DD-70, BPAF, BPSIP), and 17β estradiol (E2). Results were compared to an earlier study that evaluated the same endpoints for these chemicals in CEH. BPA and the replacement compounds had LC50 values ranging from 16.6 to 81.8 μM; DD-70 and BPAF were the most cytotoxic replacements (LC50 = 17.23 ± 4.51 and 16.6 ± 4.78 μM). TGSH and DD-70 modulated the greatest number of genes, although fewer than observed in CEH. Based on the expression of apovitellenin and vitellogenin, BPAF was the most estrogenic compound followed by BPF, BPSIP, and BPA. More estrogen-responsive genes were modulated in LMH spheroids compared to CEH. Concentration-dependent gene expression revealed that DD-70 and BPAF altered genes related to lipid and bile acid regulation. Overall, cytotoxicity and clustering of replacements based on gene expression profiles were similar between LMH spheroids and CEH. In addition to generating novel gene expression data for five BPA replacement compounds in an in vitro avian model, this research demonstrates that LMH spheroids may represent a useful animal free alternative for avian toxicity testing.

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Section: Resultssupporting

confidence: 92%

Toxicity screening of bisphenol A replacement compounds: cytotoxicity and mRNA expression in LMH 3D spheroids

Sharin

Crump

O’Brien

2022

Environ Sci Pollut Res

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“…There is a long tradition of using avian embryos to study sexual development and potential effects of environmental pollutants including EDCs ( Berg et al, 1998 ; Berge et al, 2004 ; Biau et al, 2007 ; Eising et al, 2001 ; Estermann, Major & Smith, 2021 ; Fry & Toone, 1981 ; Ioannidis et al, 2021 ). It is well known that the exposure of xenobiotics during avian embryonic development can induce irreversible deformities or malformations of the sex organs and disrupt sex-specific behavior ( Farhat et al, 2020 ; Guioli et al, 2020 ; Harnett et al, 2021 ; Mentor et al, 2020a ; Mentor et al, 2020b ; Ottinger et al, 2008 ; Quinn, Summitt & Ottinger, 2008 ; Sharin et al, 2021 ). One advantage is that the avian egg can be considered as a closed system lacking any exchange with its environment except for the interchange of gases.…”

Section: Introductionmentioning

confidence: 99%

No effects of the antiandrogens cyproterone acetate (CPA), flutamide and p,p’-DDE on early sexual differentiation but CPA-induced retardation of embryonic development in the domestic fowl (Gallus gallus domesticus)

Jessl,

Oehlmann

2023

PeerJ

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Because a wide range of environmental contaminants are known to cause endocrine disorders in humans and animals, in vivo tests are needed to identify such endocrine disrupting chemicals (EDCs) and to assess their biological effects. Despite the lack of a standardized guideline, the avian embryo has been shown to be a promising model system which responds sensitively to EDCs. After previous studies on the effects of estrogenic, antiestrogenic and androgenic substances, the present work focuses on the effects of in ovo exposure to p,p’-DDE, flutamide and cyproterone acetate (CPA) as antiandrogenic model compounds regarding gonadal sex differentiation and embryonic development of the domestic fowl (Gallus gallus domesticus). The substances were injected into the yolk of fertilized eggs on embryonic day one. On embryonic day 19 sex genotype and phenotype were determined, followed by gross morphological and histological examination of the gonads. Treatment with flutamide (0.5, 5, 50 µg/g egg), p,p’-DDE (0.5, 5, 50 µg/g egg) or CPA (0.2, 2, 20 µg/g egg) did not affect male or female gonad development, assessed by gonad surface area and cortex thickness in both sexes and by the percentage of seminiferous tubules in males as endpoints. This leads to the conclusion that antiandrogens do not affect sexual differentiation during embryonic development of G. gallus domesticus, reflecting that gonads are not target organs for androgens in birds. In ovo exposure to 2 and 20 µg CPA/g egg, however, resulted in significantly smaller embryos as displayed by shortened lengths of skull, ulna and tarsometatarsus. Although gonadal endpoints were not affected by antiandrogens, the embryo of G. gallus domesticus is shown to be a suitable test system for the identification of substance-related mortality and developmental delays.

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In silico analysis of endocrine‐disrupting potential of triclosan, bisphenol A, and their analogs and derivatives

Đurić,

Milanović,

Drljača Lero

et al. 2024

J of Applied Toxicology

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Owning to the increasing body of evidence about the ubiquitous exposure to endocrine disruptors (EDCs), particularly bisphenol A (BPA), and associated health effects, BPA has been gradually substituted with insufficiently tested structural analogs. The unmanaged excessive use of antimicrobial agents such as triclosan (TCS) during the COVID‐19 outbreak has also raised concerns about its possible interferences with hormonal functions. The similarity of BPA and estradiol, as well as TCS and non‐steroidal estrogens, imply that endocrine‐disrupting properties of their analogs could be predicted based on the chemical structure. Hence, this study aimed to evaluate the endocrine‐disrupting potential of BPA substitutes as well as TCS derivatives and degradation/biotransformation metabolites, in comparison to BPA and TCS based on their molecular properties, computational predictions of pharmacokinetics and binding affinities to nuclear receptors. Based on the obtained results several under‐researched BPA analogs exhibited higher binding affinities for nuclear receptors than BPA. Notable analogs included compounds detected in receipts (DD‐70, BTUM‐70, TGSA, and BisOPP‐A), along with a flame retardant, BDP. The possible health hazards linked to exposure to TCS and its mono‐hydroxylated metabolites were also found. Further research is needed in order to elucidate the health impacts of these compounds and promote better regulation practices.

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Effects of two Bisphenol A replacement compounds, 1,7-bis (4-hydroxyphenylthio)-3,5-dioxaheptane and Bisphenol AF, on development and mRNA expression in chicken embryos

Cited by 3 publications

References 46 publications

Toxicity screening of bisphenol A replacement compounds: cytotoxicity and mRNA expression in LMH 3D spheroids

Toxicity screening of bisphenol A replacement compounds: cytotoxicity and mRNA expression in LMH 3D spheroids

No effects of the antiandrogens cyproterone acetate (CPA), flutamide and p,p’-DDE on early sexual differentiation but CPA-induced retardation of embryonic development in the domestic fowl (Gallus gallus domesticus)

In silico analysis of endocrine‐disrupting potential of triclosan, bisphenol A, and their analogs and derivatives

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