Introduction: The ecological relevance of chemically induced endocrine disruption in wildlife

This article is part of the monograph “The Ecological Relevance of Chemically Induced Endocrine Disruption in Wildlife.

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

Validation of a method for measuring sperm quality and quantity in reproductive toxicity tests with pair-breeding male fathead minnows (Pimephales promelas)

This article originally appeared in the ILAR e-Journal. It is reprinted with permission from the ILAR Journal, Institute for Laboratory Animal Research, National Research Council, Washington DC (www.nationalacademies.org/ilar).The fathead minnow (Pimephales promelas) is an OECD-proposed test species routinely used in reproductive toxicity trials with suspected endocrine-disrupting compounds (EDCs). The basic fecundity, endocrinology, and histopathology of reproductively active male and female fathead minnows has been well characterized, but there are few studies of the utility of male sperm concentration and motility as endpoints for use in reproductive trials. The purpose of this study was to (1) characterize the baseline sperm concentration and motility of pair-breeding male fathead minnows over their spawning cycle and (2) determine whether a repeated and nondestructive sperm sampling protocol would influence the baseline fecundity of the fish. Pair-breeding male fathead minnows that underwent sampling for milt three times a week for 4 weeks exhibited no significant changes in milt volume, sperm concentration, or motility parameters up to 6 days after each spawning event. The repeated sperm sampling procedure did, however, cause a significant lowering of spawning frequencies, although this decline did not correlate with effects on fecundity as there were no significant changes in the mean total numbers of eggs laid, fertilization, and hatching successes. This study confirmed the presence of a stable background of sperm concentration and motility parameters of pair-breeding male fathead minnows under reference conditions. The absence of any inherent “cycling” in the magnitude of these parameters over the spawning period suggests that sperm concentration and motility could be useful measures of male reproductive toxicity at the termination of tests in which pair-breeding males are at varying days post spawn.The research described was funded by the EU project Comparative Research on Endocrine Disrupters (COMPRENDO) Institute of Zoology Regents Park, London, contract No. EVK1-CT-2002-00129E

Introduction: Endocrine Disruptors—Exposure Assessment, Novel End Points, and Low-Dose and Mixture Effects

With the aim of discussing new research findings about chemicals able to interfere with the endocrine system, so-called endocrine disruptors, an international workshop was held in Prague, Czech Republic, 10–12 May 2005. The workshop was organized jointly by the EDEN project (Endocrine Disrupters: Exploring Novel Endpoints, Exposure, Low-Dose and Mixture-Effects in Humans, Aquatic Wildlife and Laboratory Animals; http://www.edenresearch.info) and the FIRE project (Risk Assessment of Brominated Flame Retardants as Suspected Endocrine Disrupters for Human and Wildlife Health; http://www.rivm.nl/fire), both large-scale consortia funded by the European Union (EU). The meeting was attended by more than 170 scientists from academia, industry, government agencies, and other organizations

Environmental concentrations of anti-androgenic pharmaceuticals do not impact sexual disruption in fish alone or in combination with steroid oestrogens

This article has been made available through the Brunel Open Access Publishing Fund.Sexual disruption in wild fish has been linked to the contamination of river systems with steroid oestrogens, including the pharmaceutical 17α-ethinylestradiol, originating from domestic wastewaters. As analytical chemistry has advanced, more compounds derived from the human usage of pharmaceuticals have been identified in the environment and questions have arisen as to whether these additional pharmaceuticals may also impact sexual disruption in fish. Indeed, pharmaceutical anti-androgens have been shown to induce such effects under laboratory conditions. These are of particular interest since anti-androgenic biological activity has been identified in the aquatic environment and is potentially implicated in sexual disruption alone and in combination with steroid oestrogens. Consequently, predictive modelling was employed to determine the concentrations of two anti-androgenic human pharmaceuticals, bicalutamide and cyproterone acetate, in UK sewage effluents and river catchments and their combined impacts on sexual disruption were then assessed in two fish models. Crucially, fish were also exposed to the anti-androgens in combination with steroid oestrogens to determine whether they had any additional impact on oestrogen induced feminisation. Modelling predicted that the anti-androgenic pharmaceuticals were likely to be widespread in UK river catchments. However, their concentrations were not sufficient to induce significant responses in plasma vitellogenin concentrations, secondary sexual characteristics or gross indices in male fathead minnow or intersex in Japanese medaka alone or in combination with steroid oestrogens. However, environmentally relevant mixtures of oestrone, 17β-oestradiol and 17α-ethinylestradiol did induce vitellogenin and intersex, supporting their role in sexual disruption in wild fish populations. Unexpectedly, a male dominated sex ratio (100% in controls) was induced in medaka and the potential cause and implications are briefly discussed, highlighting the potential of non-chemical modes of action on this endpoint

Is there a causal association between genotoxicity and the imposex effect?

There is a growing body of evidence that indicates common environmental pollutants are capable of disrupting reproductive and developmental processes by interfering with the actions of endogenous hormones. Many reports of endocrine disruption describe changes in the normal development of organs and tissues that are consistent with genetic damage, and recent studies confirm that many chemicals classified to have hormone-modulating effects also possess carcinogenic and mutagenic potential. To date, however, there have been no conclusive examples linking genetic damage with perturbation of endocrine function and adverse effects in vivo. Here, we provide the first evidence of DNA damage associated with the development of imposex (the masculinization of female gastropods considered to be the result of alterations to endocrine-mediated pathways) in the dog-whelk Nucella lapillus. Animals (n = 257) that displayed various stages of tributyltin (TBT)-induced imposex were collected from sites in southwest England, and their imposex status was determined by physical examination. Linear regression analysis revealed a very strong relationship (correlation coefficient of 0.935, p < 0.0001) between the degree of imposex and the extent of DNA damage (micronucleus formation) in hemocytes. Moreover, histological examination of a larger number of dog-whelks collected from sites throughout Europe confirmed the presence of hyperplastic growths, primarily on the vas deferens and penis in both TBT-exposed male snails and in females that exhibited imposex. A strong association was found between TBT body burden and the prevalence of abnormal growths, thereby providing compelling evidence to support the hypothesis that environmental chemicals that affect reproductive processes do so partly through DNA damage pathways

Modeling the Demographic Effects of Endocrine Disruptors

In this article we describe a series of strategic models of populations and individuals subject to challenge by endocrine disruptors. These models are not designed to be fitted to detailed data on specific species but rather are intended to provide general insights on the relative importance of different demographic mechanisms in the population context. Therefore, the models contain the minimum necessary biological detail, but in recompense they are highly accessible to mathematical analysis. We show that, over a range of models with contrasting biological detail, population viability is controlled by the number of female offspring that result from the average female’s lifetime reproductive activity. Thus, male fertility changes have little effect at the population level until they become severe enough to reduce this average female output. We argue that in many circumstances endocrine disruptors are likely to produce directly deleterious effects on female fecundity at levels far below those required to reduce male fertility to dangerously low levels. Finally, we formulate a simple model of individual energetics that we argue can form the basis of a strategic discussion of the likely sensitivity of female demographic parameters to chemically induced changes in physiological function

Gestational and lactational exposure of rats to xenoestrogens results in reduced testicular size and sperm production

EHP is a publication of the U.S. government. Publication of EHP lies in the public domain and is therefore without copyright. Research articles from EHP may be used freely; however, articles from the News section of EHP may contain photographs or figures copyrighted by other commercial organizations and individuals that may not be used without obtaining prior approval from both the EHP editors and the holder of the copyright. Use of any materials published in EHP should be acknowledged (for example, "Reproduced with permission from Environmental Health Perspectives") and a reference provided for the article from which the material was reproduced.This study assessed whether exposure of male rats to two estrogenic, environmental chemicals, 4-octylphenol (OP) and butyl benzyl phthalate (BBP) during gestation or during the first 21 days of postnatal life, affected testicular size or spermatogenesis in adulthood (90-95 days of age). Chemicals were administered via the drinking water or concentrations of 10-1000 micrograms/l (OP) or 1000 micrograms/l (BBP), diethylstilbestrol (DES; 100 micrograms/l) and an octylphenol polyethoxylate (OPP; 1000 micrograms/l), which is a weak estrogen or nonestrogenic in vitro, were administered as presumptive positive and negative controls, respectively. Controls received the vehicle (ethanol) in tap water. In study 1, rats were treated from days 1-22 after births in studies 2 and 3, the mothers were treated for approximately 8-9 weeks, spanning a 2-week period before mating throughout gestation and 22 days after giving birth. With the exception of DES, treatment generally had no major adverse effect or body weight: in most instances, treated animals were heavier than controls at day 22 and at days 90-95. Exposure to OP, OPP, or BBP at a concentration of 1000 micrograms/1 resulted in a small (5-13%) but significant (p < 0.01 or p < 0.0001) reduction in mean testicular size in studies 2 and 3, an effect that was still evident when testicular weight was expressed relative to body, weight or kidney weight. The effect of OPP is attributed to its metabolism in vivo to OP. DES exposure caused similar reductions in testicular size but also caused reductions in body weight, kidney weight, and litter size. Ventral prostate weight was reduced significantly in DES-treated rats and to minor extent in OP-treated rats. Comparable but more minor effects of treatment with DES or OP on testicular size were observed in study 1. None of the treatments had any adverse effect on testicular morphology or on the cross-sectional area of the lumen or seminiferous epithelium at stages VII-VIII of the spermatogenic cycle, but DES, OP, and BBP caused reductions of 10-21% (p < 0.05 to p < 0.001) in daily sperm production. Humans are exposed to phthalates, such as BBP, and to alkylphenol polyethoxylates, such as OP, but to what extent is unknown. More detailed studies are warranted to assess the possible risk to the development of the human testis from exposure to these and other environmental estrogens

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

The consequences of feminization in breeding groups of wild fish

EHP is a publication of the U.S. government. Publication of EHP lies in the public domain and is therefore without copyright. Research articles from EHP may be used freely; however, articles from the News section of EHP may contain photographs or figures copyrighted by other commercial organizations and individuals that may not be used without obtaining prior approval from both the EHP editors and the holder of the copyright. Use of any materials published in EHP should be acknowledged (for example, "Reproduced with permission from Environmental Health Perspectives") and a reference provided for the article from which the material was reproduced.BACKGROUND: The feminization of nature by endocrine-disrupting chemicals (EDCs) is a key environmental issue affecting both terrestrial and aquatic wildlife. A crucial and as yet unanswered question is whether EDCs have adverse impacts on the sustainability of wildlife populations. There is widespread concern that intersex fish are reproductively compromised, with potential population-level consequences. However, to date, only in vitro sperm quality data are available in support of this hypothesis. OBJECTIVE: The aim of this study was to examine whether wild endocrine-disrupted fish can compete successfully in a realistic breeding scenario. METHODS: In two competitive breeding experiments using wild roach (Rutilus rutilus), we used DNA microsatellites to assign parentage and thus determine reproductive success of the adults. RESULTS: In both studies, the majority of intersex fish were able to breed, albeit with varying degrees of success. In the first study, where most intersex fish were only mildly feminized, body length was the only factor correlated with reproductive success. In the second study, which included a higher number of more severely intersex fish, reproductive performance was negatively correlated with severity of intersex. The intersex condition reduced reproductive performance by up to 76% for the most feminized individuals in this study, demonstrating a significant adverse effect of intersex on reproductive performance. CONCLUSION: Feminization of male fish is likely to be an important determinant of reproductive performance in rivers where there is a high prevalence of moderately to severely feminized males.Funding for this work was derived through the Endocrine Disruption in Catchments project, which was supported by the U.K. Department for Environment Food and Rural Affairs and the U.K. Environment Agency