Impacts of Endocrine Disrupting Chemicals on Reproduction in Wildlife

 

Main effects and comments

Annelida

These species produce and respond to estrogens. Numerous EDCs activate or antagonise the estrogen receptors (ER) and modulate vitellogenin production (Keay and Thornton 2009; Matozzo et al. 2008)

Mollusca

Molluscs appear to have estrogen-like receptors, but they apparently are not activated by vertebrate estrogen, estradiol, or by other known vertebrate EDCs. Nevertheless, mud snails responded to 12.5 and 25 % sewage by increased embryo production, while higher sewage concentration (50 %) reduced it (Jobling et al. 2004). Similar studies on sewage exposure have detected increased vitellogenin-like proteins in males, feminised sex ratios and low gonadosomic indices. Varying degrees of intersex also reported in over 20 % of individual bivalves (Scrobicularia plana) sampled from 17 out of 23 British estuaries (Gomes et al. 2009; Chesman and Langston 2006)

Bisphenol A (BPA) was reported to act as an estrogen receptor agonist in ramshorn snails because effects were antagonized by co-exposure to ER-antagonists (Oehlmann et al. 2006). These results could not be replicated by Forbes et al. (2008) and remain controversial

Potent androgen receptor agonists and aromatase inhibitors, as well as marine anti-fouling paint component tributyl tin (TBT), induce “imposex” in female gastropod molluscs at concentrations as low as parts per billion (Horiguchi 2006). This is where the penis “imposes” on the normal female anatomy, blocking the oviduct and inducing sterility (Pascoal et al. 2013)

Crustacea

Control of development requires neuropeptides, ecdysone and methyl farnesoate, but little is known about the identities of chemicals in the environment that may disrupt the signalling processes at relevant concentrations (European Environment Agency 2012)

Cnidarians

The phylum Cnidaria contains four extant classes, the Hydrozoa (e.g., hydras), Scyphozoa (“true” jellyfishes), Cubozoa (box jellies) and Anthozoa (e.g., corals and anemones). Endocrine disruption has not been documented in cnidarians (Tarrant 2007; Armoza-Zvuloni et al. 2012). Hormonal signalling pathways are poorly characterized and few appropriate endpoints have been established

Terrestrial invertebrates

Little attention has been paid to EDC effects in terrestrial invertebrates, although several isolated studies have been published. A cell line from Drosophila melanogaster was developed for use in a rapid screening assay for ecdysteroid receptor agonists and antagonists (Dinan et al. 2001a, b). The only pharmaceutical showing detectable EDC activity activity was 17alpha-ethynylestradiol. Many compounds were inactive over a wide concentration range or cytotoxic at high concentrations. However, antagonistic activity was associated with several classes of compounds: cucurbitacins and withanolides, phenylalkanoids and certain alkaloids described for the first time





4 What Should Be Done?


The title of this subsection is unashamedly copied from a review by the late Dr Stuart Rhind (Rhind 2009) who presented it by invitation at a symposium of the Zoological Society of London in 2009 organized by one of the present authors (WVH). Apart from providing an excellent overview of the entire field, Dr Rhind memorably discussed an experiment in which sheep grazed on land that had been fertilized twice yearly using sewage sludge were compared with sheep that were grazed on untreated grass. Analyses showed that soil levels of contaminants such as phthalate and alkyl phenol PCB and PBDE were initially very low and were increased only minimally by the sewage treatment (Rhind et al. 2002). Nevertheless, when the reproductive performance of the experimentally exposed sheep was investigated, it was found that the testes of their fetuses contained fewer Leydig and Sertoli cells than the controls, coupled with lower blood concentrations of the hormones testosterone and inhibin (Paul et al. 2005). There were also fewer oocytes in the fetal ovaries (Fowler et al. 2008) and an altered balance of pro- and anti-apoptotic proteins towards apoptosis. This remarkable outcome can be regarded as a “real world” effect that probably applies not only to grazing domestic sheep but also many other terrestrial species, especially those whose habitats are likely to have suffered any form of airborne or waterborne pollution. Subtleties such as the reduction of oocyte and Sertoli cell production (which would both result in lowered gamete production) by mammalian fetuses are likely to be undetectable in wild and threatened species, because, by definition, these species are not intensely studied. Nevertheless, the outcome of such effects will ultimately be reflected in lowered fertility, an undesirable outcome under the circumstances.

As discussed elsewhere in this book, however, the way in which different species are affected cannot necessarily be predicted, given the huge diversity of reproductive mechanisms that have evolved to cope with different, and often very adverse, conditions. Improving our understanding of comparative reproductive mechanisms is therefore as essential in this, as it is in related fields. The outcomes of many field observations, especially those involving complex mixtures of chemicals, underline the crudeness of our understanding of mixtures, and the way in which they affect reproductive mechanisms. This is understandable because experimental laboratory scientists typically prefer to make sure they understand the variables in their treatments. Although regulatory initiatives such as that introduced in 2006 by the European Union, namely Registration, Evaluation, Authorization and Restriction of chemical substances (REACH), will provide basic toxicity data on the all chemicals produced in Europe or imported into Europe in amounts that exceed 100 t per annum, the enormous number of chemicals that REACH is expected to evaluate (143,000 were pre-registered with REACH in 2008) will preclude all but the most limited of testing regimes. In fact, under the REACH protocols all substances are only tested once. This is a massive undertaking and it is interesting to see that the policy itself has been criticised because of the extensive need for animal testing (Hartung and Rovida 2009); these authors suggested that 54 million vertebrate animals would be used under REACH and that the costs would be around €9.5 billion.

One conclusion to be drawn is that there is a pressing need for the further development of reliable tests that can be used in vitro to assess the toxicity of chemicals, thereby avoiding animal use. Some authors such as Schrattenholz et al. (2012) have considered that multifactorial systems biology may be useful for this purpose because of the possibility of integrating data across transcriptomics, proteomics, epigenomics and metabolomics. Others such as Lee et al. (2012) have proposed the use of whole embryo culture and mouse embryonic stem cells as alternative models for the study of developmental toxicology. Focusing on species of most ecological relevance has led some authors, such as Scholz et al. (2013), to concentrate on fish and amphibian cells for toxicity testing, while others have applied the same principle to the evaluation of chemicals that would be particularly relevant in terms of marine species such as corals (Shafir et al. 2003: Howe et al. 2012).

The studies cited in this short chapter underline and emphasise the vast amount of work that has been carried out over the past few decades, and it is apparent that although international regulatory authorities are now taking note of the need to prevent some of the worst chemicals from reaching the environment, the problems are global, multifactorial and difficult.


Acknowledgements 

The authors are grateful to Dr Alice Baynes (Brunel University, Uxbridge, UK) for her constructive comments during preparation of this article.


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