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Research presented as part of a conference abstract at the European Congress of Endocrinology annual meeting suggests that exposure to environmental pollutants can cause alterations in brain development that affect sexual development and fertility for several generations.
Dr Rod Mitchell, Consultant Paediatric Endocrinologist & Group Leader, MRC Centre for Reproductive Health, University of Edinburgh, said:
“From the limited information presented in the abstract, it is not possible to conclude on the validity of the science or experimental approach.”
“The study requires robust peer-review before any conclusions can be made and it should also be recognised that previous studies have shown that the reproductive effects of in-utero chemical exposure in rodents cannot be directly translated to humans.”
“Even if the findings of this study in rats proved to be robust following independent expert review, the relevance of exposure to such a mixture of chemicals in relation to humans and human health would still require further investigation.”
Prof Richard Sharpe, Honorary Professor, MRC Centre for Reproductive Health, University of Edinburgh, said:
“In principle the type of findings reported in this study fit with earlier published findings in showing that exposures (dietary, or experimental exposures) during pregnancy can result in pathophysiological changes to both males and females of subsequent generations via non-genetic mechanisms; these mechanisms are presumed to be epigenetic and/or behavioural. But for the most part direct evidence of such mechanisms has not yet been proven (and is technically very challenging). Therefore, the findings reported are consistent with what we are increasingly recognising as being possible.
“My biggest concern is with the overall interpretation, especially that the changes induced are the result of exposure to a mixture of EDCs, because one of the compounds used in the mixture is a pharmaceutical (paracetamol), and we and others have shown that pregnancy exposure of rats or mice to human therapeutic levels of paracetamol can induce reproductive changes in offspring of at least two generations with transmission of effects via both male and female lines (ie derived from males or females that were exposed in utero). Based on this, it might be that all/most of the effects observed in the present studies are the result of exposure to just the paracetamol with no effect of the other compounds. It would have been better if an EDC mixture of environmental compounds, to which we are exposed at very low levels was not mixed with a highly potent pharmaceutical that would have been administered at very high levels (in comparison to the EDC pollutants/contaminants), even though these high levels are human-relevant. It means that without a ‘control’ exposure group lacking paracetamol, it is not possible for the authors to claim that it is the overall mixture that causes the effects they observe.
“An ever-present concern is also what level of exposure to the EDCs, other than paracetamol, were used. It is common for authors to glibly describe the exposure levels as being comparable to human exposure, but reviews of such studies has shown that the actual levels used can vary by up to 3 or more orders of magnitude and are rarely true reflections of human everyday exposure; as no figures were provided, it is not possible to be sure how human-relevant the actual exposures would have been.
“Finally, studies involving multigenerations are extremely challenging to undertake as they are incredibly laborious and costly to undertake with scientific rigour. As no details of the study animal numbers and selection from one generation to the next are provided, it is not possible to know what the quality and rigour of this study was. Such issues are always frontline when such studies are being assessed for publication in the peer-reviewed literature.”
Dr Channa Jayasena, Clinical Senior Lecturer in Reproductive Endocrinology, Imperial College London, said:
“Worldwide fertility rates are dropping. EDCs are human-made chemicals that get into our food chain, which some suspect may contribute to this drop. Unfortunately, some of these chemicals can fool the body to thinking they are hormones like oestrogen or testosterone, which means they could affect reproduction. Several studies have reported that sexual development may be affected by EDCs. This study exposed rats to EDCs during pregnancy; their ‘kids’ and ‘grandkids’ were never exposed to the EDCs but did have problems with puberty and fertility. A big problem with studying EDCs in humans is that everyone is exposed, so clinical trials cannot be conducted. The methods and conclusions of their preliminary work appear thorough and appropriate, although the full results would need to be published before we can make concrete conclusions. Nevertheless, this study emphasises the potentially important detrimental effects of EDCs to human health.”
Prof Kevin McConway, Emeritus Professor of Applied Statistics, The Open University, said:
“There are lots of questions that I’d want to be answered about this study before I can decide on its importance and quality. How well does the mixture of chemicals to which these rats were exposed resemble what people might be exposed to in their everyday activities? How well do the doses correspond to what humans might encounter? It’s not always straightforward to match doses between humans and small animals like rats. What evidence might there be that the genetics works in similar ways in humans and rats? Sometimes results of animal studies do turn out to apply to humans as well, but often they do not.
“As a statistician, I’d certainly want to know how many rats were involved and how the results were processed statistically, so I could be confident that the reported results properly summarise what was found. But I don’t know the answers to any of those things, because the study hasn’t yet been published in full. All we have is a conference abstract and press release. The research won’t yet have been through the full process of peer review, so other scientists won’t have evaluated and checked all these details either. So, for now at least, I really can’t make a judgment on this work at all.”
Prof Stephen Evans, Professor of Pharmacoepidemiology, London School of Hygiene & Tropical Medicine (LSHTM), said:
“The description of the methods and the results lacks any numerical data or the associated uncertainty, so it cannot be assessed by independent scientists with any rigour. Everything has to be taken on trust. Using mixtures of products in this way does not enable any understanding of possible mechanisms.
“It may be good science but the description does not allow a judgement to be made on its validity.”
Abstract title: ‘Endocrine Disruptors transgenerationally alters pubertal timing through epigenetic reprogramming of the hypothalamus’ by Lopez Rodriguez et al was presented on Monday 20 May 2019, at the European Congress of Endocrinology annual meeting.
Declared interests
Prof Richard Sharpe: “I have no conflicts of interest.”
Dr Channa Jayasena: “No conflicts to declare.”
Prof Kevin McConway: Prof McConway is a member of the SMC Advisory Committee, but his quote above is in his capacity as a professional statistician.
None others received.