The effects of marginal maternal vitamin A status on penta‐brominated diphenyl ether mixture‐induced alterations in maternal and conceptal vitamin A and fetal development in the Sprague Dawley rat

Ellis-Hutchings, Robert G.; Cherr, Gary N.; Hanna, Lynn A.; Keen, Carl L.

doi:10.1002/bdrb.20181

Cited by 13 publications

(3 citation statements)

References 48 publications

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“…Moreover, the condition of marginal vitamin A deficiency renders rodents significantly more sensitive to the TH-lowering effect of PBDEs. 82 These novel studies indicate that PBDE exposure may exert independent effects on circulating levels of thyroid hormone and vitamin A, but that the cross-talk between these two signaling systems may be a target of PBDE action.…”

Section: Polybrominated Diphenyl Ethers (Pbdes)mentioning

confidence: 99%

Environmental chemicals targeting thyroid

Zoeller¹

2010

133

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Thyroid hormones (THs) are required for normal brain and somatic development and for the proper regulation of physiology in both children and adults. Thyroid function is controlled by the dynamic interrelationships between the hypothalamus, the pituitary and the thyroid. These dynamic relationships maintain circulating levels of THs within a narrow range under normal conditions. Normally, there is likely to be a tight relationship between changes in circulating levels of THs and changes in TH action in various target tissues. This relationship is maintained by tissue-level mechanisms that include TH metabolism and transport. Environmental chemicals that interfere with TH signaling mechanisms (Endocrine Disrupting chemicals, EDcs) may produce adverse effects both in the individual and in a population. Because of the complex nature of the regulation of thyroid function and TH action, the consequences of EDc exposure is also likely to be complex and our ability to understand these effects as well as to screen for potential EDcs must consider this complexity. Specifically, if there are chemicals in the environment that directly interfere with TH action through their receptors but do not affect circulating TH levels, they would not be identified as thyroid toxicants by currently applied screening methods or by epidemiological studies. The goal of this review is therefore to identify the issues that must be clearly resolved before effective risk assessment can be performed. HORMONES 2010, 9(1) the hypothalamic pituitaRy thyRoid axis (hpt) axis To develop efficient risk assessment strategies for thyroid toxicants, it is important to understand both the normal functioning of the hypothalamic-pituitary-thyroid axis (HPT) and what we know about individual thyroid toxicants. To this end, background information about the HPT axis and its relevance to thyroid toxicology is reviewed here. Key words: Thyroid hormones, Endocrine disruptors, Environmental chemicals, Thyroid toxicants ReviewCirculating levels of Thyroid Hormones (THs) are maintained within a relatively narrow range 1 in large part by a negative feedback relationship between circulating levels of THs and those of Thyroid Stimulating Hormone (TSH). THs appear to exert this effect by acting on one subtype of the TH receptor (TR). TRs are encoded by two separate genes,  and , the primary transcripts of which are alternatively spliced

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Section: Polybrominated Diphenyl Ethers (Pbdes)mentioning

confidence: 99%

Environmental chemicals targeting thyroid

Zoeller¹

2010

133

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“…13,14 During embryonic development, THR mRNA expression can vary considerably with age and by species. In rodents, THR mRNA is expressed in the developing middle ear and nearby brain tissue, suggesting that it is related to central nervous system development, 15,16 In addition, THRβ is also known to play a key role in pituitary and liver thyroid hormone metabolism in rats.…”

Section: Introductionmentioning

confidence: 99%

The PBDE metabolite 6-OH-BDE 47 affects melanin pigmentation and THRβ MRNA expression in the eye of zebrafish embryos

Wang

Macaulay

Kwok³

et al. 2014

Endocrine Disruptors

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Polybrominated diphenyl ethers and their hydroxyl-metabolites (OH-BDEs) are commonly detected contaminants in human serum in the US population. They are also considered to be endocrine disruptors, and are specifically known to affect thyroid hormone regulation. In this study, we investigated and compared the effects of a PBDE and its OH-BDE metabolite on developmental pathways regulated by thyroid hormones using zebrafish as a model. Exposure to 6-OHBDE 47 (10–100 nM), but not BDE 47 (1–50 μM), led to decreased melanin pigmentation and increased apoptosis in the retina of zebrafish embryos in a concentration-dependent manner in short-term exposures (4 – 30 hours). Six-OH-BDE 47 exposure also significantly decreased thyroid hormone receptor β (THRβ) mRNA expression, which was confirmed using both RT-PCR and in situ hybridization (whole mount and paraffin- section). Interestingly, exposure to the native thyroid hormone, triiodothyronine (T3) also led to similar responses: decreased THRβ mRNA expression, decreased melanin pigmentation and increased apoptosis, suggesting that 6-OH-BDE 47 may be acting as a T3 mimic. To further investigate short-term effects that may be regulated by THRβ, experiments using a morpholino gene knock down and THRβ mRNA over expression were conducted. Knock down of THRβ led to decreases in melanin pigmentation and increases in apoptotic cells in the eye of zebrafish embryos, similar to exposure to T3 and 6-OH-BDE 47, but THRβ mRNA overexpression rescued these effects. Histological analysis of eyes at 22 hpf from each group revealed that exposure to T3 or to 6-OH-BDE 47 was associated with a decrease of melanin and diminished proliferation of cells in layers of retina near the choroid. This study suggests that 6-OH-BDE 47 disrupts the activity of THRβ in early life stages of zebrafish, and warrants further studies on effects in developing humans.

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“…valproic acid), flame retardants (e.g. polybrominated diphenyl ethers), plasticizers (phthalate esters), and pesticides (triazole fungicides) have been reported to alter retinoid signalling biomarkers and induce retinoid-like teratogenic effects [111,[167][168][169][170] (see also Table 1). Exposure assessment of pharmaceuticals with the retinoid mode of action may require different regulatory approaches, depending upon the route of exposure, i.e.…”

Section: Phenotypic Patterns Of Interference With Retinoid Signallingmentioning

confidence: 99%

Highlighting the gaps in hazard and risk assessment of unregulated Endocrine Active Substances in surface waters: retinoids as a European case study

et al. 2021

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Regulatory hazard and risk assessment of endocrine-active substances currently specifies four modes of action: interference with sex hormone (oestrogen, androgen) pathways, steroidogenesis, and thyroid hormone signalling. This does not encompass the full complexity of the endocrine system and its extended interfaces with environmental pollutants that can potentially disrupt the carefully maintained balance. Here we take the retinoid signalling pathway as a European case study for both, under- and unregulated endocrine pathways and outline the different levels of interference, discuss their adversity, and indicate crosstalk to other signalling pathways. Retinoid compounds already exist in drinking water sources, occur naturally in cyanobacterial blooms and/or enter surface waters via wastewater discharge, where they pose a potential hazard to the environment and human health - a situation that can be expected to worsen due to water shortages induced by climate-change and population growth. We briefly review relevant aspects of current endocrine disruptor (ED) testing for regulatory purposes and then expand upon the needs for inclusion of disruption of retinoid signalling in (ED) regulatory safety assessment contributing to adverse health outcomes that include cognitive function and neurological disease. An overview of developmental effects of retinoid signalling disruption across species highlights critical processes and potential crosstalk with other signalling pathways. A focused weight of evidence-based evaluation of the biologically plausible associations between neurological disorders and altered retinoid signalling highlights the evidence gaps. We show that monitoring only a limited number of anthropogenic priority chemicals in water is insufficient to address the environmental risks of retinoid signalling disruption. To comprehensively assess impacts on the endpoints, processes, and pathways of the endocrine system that are most vulnerable to chemical interference we need further investigation of the true mixture composition in environmental matrices. On a weight of evidence-basis this information can then be integrated into a reliable, inclusive, quantitative approach that ultimately accommodates all the critical pathways. By focusing on the retinoid signalling pathway, we intend to improve the scope and relevance of an integrated approach for the risk assessment of endocrine disruptors.

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The effects of marginal maternal vitamin A status on penta‐brominated diphenyl ether mixture‐induced alterations in maternal and conceptal vitamin A and fetal development in the Sprague Dawley rat

Abstract: The results of this study support the concept that marginal vitamin A status enhances the disruptive effects of DE-71 during prenatal development.

Cited by 13 publications

References 48 publications

Environmental chemicals targeting thyroid

Environmental chemicals targeting thyroid

The PBDE metabolite 6-OH-BDE 47 affects melanin pigmentation and THRβ MRNA expression in the eye of zebrafish embryos

Highlighting the gaps in hazard and risk assessment of unregulated Endocrine Active Substances in surface waters: retinoids as a European case study

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