Endocrine disruption in wildlife: The future?

Probably the only thing that can be said with certainty about the future of this field of ecotoxicology is that predicting it is foolish; the chances of being right are very slim. Instead, it seems to me likely that unexpected discoveries will probably have more influence on the field of endocrine disruption than the outcomes of all the planned experiments. It is certainly true that chance discoveries, such as masculinized fish in rivers receiving paper-mill effluent, imposex in molluscs due to exposure to tributyltin and feminized fish in rivers receiving effluent from sewage-treatment works, have been pivotal in the development of the field of endocrine disruption in wildlife. I consider that further such discoveries are likely, but I do not know which species will be affected, what effects will be found, what chemical(s) will be the cause, or what endocrine mechanism(s) will underlie the effects. The recent realization that many pharmaceuticals are present in the aquatic environment only underscores the range of effects that could, in theory at least, occur in exposed wildlife. What is somewhat easier to predict is the research that will be conducted in the immediate future, which will build upon what is known already. For example, it is clear that wildlife is rarely, if ever, exposed to single chemicals, but instead is exposed to highly complex, ill-defined mixtures of chemicals, including many that are endocrine active in various ways. We need to understand much better how chemicals interact, and what overall effects will occur upon exposure to such mixtures. We also need to move from assessing effects at the individual organism level, to understanding the consequences of these effects at the population level. Then, we need to determine the significance of any population-level effects due to endocrine disruption in comparison with the impact of many other significant stressors (e.g., over-exploitation, habitat loss, climate change) that also negatively impact wildlife. Such research will be difficult, and time-consuming, and will probably produce many surprises. All I can be fairly certain about is that the next few years are likely to be as interesting and exciting as the last few have been

Structural features of alkylphenolic chemicals associated with estrogenic activity

The ability of certain man-made chemicals to mimic the effects of natural steroid hormones and their potential to disrupt the delicate balance of the endocrine system in animals are of increasing concern. The growing list of reported hormone-mimics includes the alkylphenolic (AP) compounds, a small number of which have been reported to be weakly estrogenic. In their most basic form, APs are composed of an alkyl group, which can vary in size, branching, and position, joined to a phenolic ring. The aim of this project was to identify the important structural features responsible for the estrogenic activity of AP chemicals. This was achieved by incubating APs with different structural features in a medium containing a previously described estrogen-inducible strain of yeast (Saccharomyces cerevisiae) expressing the human estrogen receptor and comparing their activity spectrophotometrically by the resulting color change of the medium. The results were compared to the effects of the main natural estrogen 17-estradiol. The data indicate that both the position (para > meta > ortho) and branching (tertiary > secondary = normal) of the alkyl group affect estrogenicity. Optimal estrogenic activity requires a single tertiary branched alkyl group composed of between 6 and 8 carbons located at the para position on an otherwise unhindered phenol ring. The results are discussed in relation to the purity and composition of the chemicals tested

Mixtures of Chemicals in Water: Implications of chemical legislation and environmental policy

Scientists have shown that mixtures of chemicals can act together to reduce the reproductive capacity of fish even if each individual chemical in the mixture is present at a concentration that does not cause an adverse effect. This evidence demonstrates that legislation based on the assessment of single chemicals may not be sufficiently protective and suggest that there is a need for a review of existing environmental policy

Seasonal changes in serum testosterone, 11-ketotestosterone, and 1713-estradiol levels in the brown bullhead, Ictalurus nebuIosus Lesueur

The seasonal changes in gonadosomatic index (GSI) and strum testosterone, I I-ketotestosterone, and 17&estmdiol levels were measured in adult feral brown bullheads, Ictalurus nebulosus Lzsueur. The maximum GSI of both male and femalz brown bullheads was consjderably lower than that of most other teleostean species investigated. lo males, the GSI began to increase in April concomitant with an increase in water temperature from 3 to 6°C. The maximum GSI levels were evident throu_ghout May and June (during the prespawning and spawning periods). Peaks of serum testosterone and serum 11-ketotesrosterone leveb were evident in mid-April and late May to June, and in mid-April and mid-May, respxtively. In females here was a rapid increase in GSI during May, when the ambient water temperamre reached 16°C. The peak GSI was evident in mid- to late-May and had declined by early June. Peak serum testosterone and I 1-ketotestosterone levels were evident .in mid-April and again in late May. wbereas peak 17P-estradiol levels were fou.nd in mid-May and mid-June. The peak serum teswsterone levels in females were 4.5-fold higher than in the males, whereas che I I-ketotestosterone levels were similar in males and females

Endocrine disruption in juvenile roach from English rivers: A preliminary study

Juvenile roach Rutilus rutilus from seven rivers of varying water quality were examined for evidence of endocrine disruption. The majority of roach from five of these rivers had femalelike reproductive ducts. The results suggest that juvenile, rather than adult, fish could be used in studies of endocrine disruption in wild fish populations

Estrogenic activity of phenolic additives determined by an in vitro yeast bioassay

Copyright @ 2001 Environmental Health PerspectivesWe used a recombinant yeast estrogen assay to assess the activity of 73 phenolic additives that are used as sunscreens, preservatives, disinfectants, antioxidants, flavorings, or for perfumery. Thirty-two of these compounds displayed activity: 22 with potencies relative to 17 beta -estradiol, ranging from 1/3,000 to -estradiol. Forty-one compounds were inactive. The major criteria for activity appear to be the presence of an unhindered phenolic OH group in a para position and a molecular weight of 140-250 Da.This work was supported in part under contract with the U.K. Department of Trade and Industry as part of the Government Chemist Programme

Issues arising when interpreting results from an in vitro assay for estrogenic activity

Concern about possible adverse effects caused by the inadvertent exposure of humans and wildlife to endocrine-active chemicals, has led some countries to develop an in vivo–in vitro screening program for endocrine effects. In this paper, a previously described estrogen-inducible recombinant yeast strain (Saccharomyces cerevisiae) is used to investigate a number of issues that could potentially lead to the mislabeling of chemicals as endocrine disruptors. The chemicals studied were: 17-estradiol, dihydrotestosterone, testosterone, estradiol-3-sulfate, 4-nonylphenol, 4-tert-octylphenol, 4-tert-butylphenol, bisphenol-A, methoxychlor, 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane, butyl benzyl phthalate, 4-hydroxytamoxifen, and ICI 182,780. Alterations in assay methodology (for example, incubation time, initial yeast cell number, and the use of different solvents) did not affect the potency of bisphenol-A and 4-nonylphenol relative to 17-estradiol, but did alter the apparent potency of butyl benzyl phthalate. Other issues (including the metabolic activation of methoxychlor, the chemical purity of a steroid metabolite and unusual chemical artifacts observed with alkylphenolic chemicals) which affect data interpretation are described. Many of the issues raised will also affect other in vitro assays for endocrine activity, and some will be relevant to the interpretation of data from in vivo assays. These examples illustrate that considerable care and thought must be applied when interpreting results derived from any single assay. Only by using a suite of assays will we minimize the chances of wrongly labeling chemicals as endocrine disruptors

Preliminary data on the influence of rearing temperature on the growth and reproductive status of fathead minnows Pimephales promelas

This article has been made available through the Brunel Open Access Publishing Fund and is available from the specified link - Copyright @ 2011 Brian JV et al.An investigation into the influence of temperature on the growth and reproductive status of the fathead minnow Pimephales promelas revealed that, while there was no clear effect of treatment on sex differentiation, ovarian tissue from female fish reared under the highest temperature regime contained large amounts of undefined tissue containing no germ cells. Furthermore, both male and female fish exhibited differences in length mass, condition and somatic indices, and in the expression of secondary sexual characteristics. The patterns observed are discussed in the context of climate change

Characterisation and expression of β1-, β2- and β3-adrenergic receptors in the fathead minnow (Pimephales promelas)

This is the author’s version of a work that was accepted for publication in General and Comparative Endocrinology. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published and may be accessed at the link below. Copyright © 2011 Elsevier B.V. All rights reserved.Complimentary DNAs for three beta-adrenergic receptors (βARs) were isolated and characterised in the fathead minnow. The encoded proteins of 402 (β(1)AR), 397 (β(2)AR) and 434 (β(3)AR) amino acids were homologous to other vertebrate βARs, and displayed the characteristic seven transmembrane helices of G Protein-coupled receptors. Motifs and amino acids shown to be important for ligand binding were conserved in the fathead minnow receptors. Quantitative RT-PCR revealed the expression of all receptors to be highest in the heart and lowest in the ovary. However, the β(1)AR was the predominant subtype in the heart (70%), and β(3)AR the predominant subtype in the ovary (53%). In the brain, β(1)AR expression was about 200-fold higher than that of β(2)- and β(3)AR, whereas in the liver, β(2)AR expression was about 20-fold and 100-fold higher than β(3)- and β(1)AR expression, respectively. Receptor gene expression was modulated by exposure to propranolol (0.001-1mg/L) for 21days, but not in a consistent, concentration-related manner. These results show that the fathead minnow has a beta-adrenergic receptor repertoire similar to that of mammals, with the molecular signatures required for ligand binding. An exogenous ligand, the beta-blocker propranolol, is able to alter the expression profile of these receptors, although the functional relevance of such changes remains to be determined. Characterisation of the molecular targets for beta-blockers in fish will aid informed environmental risk assessments of these drugs, which are known to be present in the aquatic environment.European Union as part of the ERAPharm project, Contract No. 511135 and NER

Vitellogenesis as a biomarker for estrogenic contamination of the aquatic environment

A rapidly increasing number of chemicals, or their degradation products, are being recognized as possessing estrogenic activity, albeit usually weak. We have found that effluent from sewage treatment works contains a chemical, or mixture of chemicals, that induces vitellogenin synthesis in male fish maintained in the effluent, thus indicating that the effluent is estrogenic. The effect was extremely pronounced and occurred at all sewage treatment works tested. The nature of the chemical or chemicals causing the effect is presently not known. However, we have tested a number of chemicals known to be estrogenic to mammals and have shown that they are also estrogenic to fish; that is, no species specificity was apparent. Many of these weakly estrogenic chemicals are known to be present in effluents. Further, a mixture of different estrogenic chemicals was considerably more potent than each of the chemicals when tested individually, suggesting that enhanced effects could occur when fish are exposed simultaneously to various estrogenic chemicals (as is likely to occur in rivers receiving effluent). Subsequent work should determine whether exposure to these chemicals at the concentrations present in the environment leads to any deleterious physiological effects