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Some suspected endocrine disruptors alter ovarian function and may contribute to female infertility

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A new study from FREIA, published in Environmental Research, explored the association between potential endocrine disrupting chemicals (EDCs) and female fertility in women attending fertility clinics in Sweden and Estonia.

Up to 1 in 6 women experience difficulties becoming pregnant or carrying pregnancy to term. Despite the increasing use of assisted reproductive technologies (ART), the success rates of these treatments remained the same.

Ovarian disorders are the cause for infertility in about 1 in 4 couples. The ovaries play an important role in hormone production and formation of oocytes (“eggs”). It is therefore reasonable to assume that human-made chemicals that disrupt the hormone system, i.e. endocrine disrupting chemicals or EDCs, contribute to the rates of infertility.

In this FREIA study, levels of 59 known and suspected EDCs were analysed in follicular fluid, the biological fluid surrounding oocytes, of 185 Swedish women and 148 Estonian women undergoing fertility treatment. Multiple chemicals were detected in all follicular fluids. In >90% of the follicular fluids, 3 metabolites of the phthalate DEHP, methylparaben, and 6 PFAS (PFOS, PFOA, PFHxS, PFUnDA, PFNA and PFDA) were detected and used to link with female fertility parameters.

The ovaries of women with higher levels of DEHP, methylparaben and possibly PFUnDA and PFOA responded less to fertility treatment, established by calculating the ovarian sensitivity index (OSI). There were indications that some PFAS lowered the success of fertility treatment, determined by chance of establishing a pregnancy or live birth.

Overall, this study provides additional evidence that DEHP can negatively influence female fertility. In addition, several other chemicals, i.e. methylparaben and some PFAS, were identified that may harm ovarian function and contribute to female infertility.

This study adds to the increasing evidence that EDCs can contribute to female infertility and warrants interventions to lower exposures.

Endocrine disruptors should not be assessed individually

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Six chemical substances possess endocrine disrupting effects – and especially combination effects when they are assessed together. Force Technology, DHI and researchers from FREIA partners at the DTU National Food Institute have performed risk assessments for the Danish Environmental Protection Agency.

Force Technology, together with DHI and researchers at the DTU National Food Institute, has evaluated six chemical substances for their risk of exerting endocrine disrupting effect.
The six substances were:

  • Butylhydroxyanisole (BHA),
  • Butylhydroxytoluene (BHT),
  • Butyl paraben,
  • Propyl paraben,
  • Octamethylcyclotetrasiloxane (D4),
  • Bisphenol A (BPA),

The risk assessment shows that exposure to the substances individually does not constitute a risk, but that the total exposure can be a cause for concern. This conclusion is based on recent exposure assessments for the six substances, as well as a hazard assessment of the substances’ endocrine disrupting properties.

The hazard assessment shows evidence that all substances have endocrine disrupting effects. However, the evidence is stronger for some of the substances (D4, BPA, butylparaben, propylparaben) than for others (BHA and BHT).

Endocrine disruptors are suspected to contribute to the increasing incidence rate of, for example, genital malformations, reduced fertility, the development of obesity and diabetes and compromised brain development. The substances can be found in a wide range of consumer products, including foods, food contact materials and medicines.

It is not enough to evaluate chemicals individually

In recent years several major research projects at the DTU National Food Institute have shown that combination effects of endocrine disruptors exist, and that these should be taken into account when risk assessing chemicals.

If you only evaluate the substances one at a time, you will underestimate the overall risk of endocrine disrupting effects. Therefore, the risk of the combined exposure from several different chemical substances from several different sources was assessed in this project.

Threshold value or not?

In EU it has been discussed in recent years whether or not there is a threshold value for lower effect of endocrine disruptors. It is possible that, as with carcinogens, there is no lower limit for endocrine disrupting effects. The calculations in the report were therefore made both with and without assumption of threshold values.

Read more

NOTE: this message was copied from the DTU website. The original message (posted 28 June 2022) can be found here.

Yuling Xie awarded Innovators Under 35 price

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Yuling Xie, Postdoctoral Researcher in the FREIA project, Queen’s University of Belfast, Belfast/UK was awarded the MIT Innovators Under 25 price. EmTech Europe unites leaders in academia, business and government to share ground breaking research-to-market advances and explore the latest breakthroughs in transformative technologies.

Since the term ‘endocrine disrupting chemicals’ (EDCs) was coined in the early 90’s, there have been calls for further research to improve our understanding of how EDCs impact both human and environmental health. The presence of endocrine disrupting chemicals in many everyday items such as clothing, food and cosmetics, makes our continuous exposure to them difficult to prevent. EDCs have not only been shown to effect fertility but may also result in transgenerational health risks, therefore research which leads to an even greater understanding of how these chemicals impact our health and cause disease is of utmost importance. 

Yuling Xie (Cher) began her research into EDCs during her postgraduate studies in Professor Lisa Connolly’s research group at Queen’s University Belfast, where she revealed how EDCs damage human health and the environment before switching her focus during her PhD to the metabolic effects of EDCs where she gained vast experience in assay development and optimisation. 

Cher has worked on developing high throughput test methods to identify chemicals with endocrine disrupting potential. Alongside her colleagues in the FREIA (Female Reproductive toxicity of EDCs: a human evidence-based screening and Identification Approach) project, Cher has expanded the knowledge of how EDCs impact female reproductive function. In addition to developing the high throughput test, Cher has also explored potential protective approaches to EDC exposure through the integration of nutritional studies to gain insight into how dietary intervention may help to counteract the negative effects of EDCs on our health. 

For more Innovators and information about the award: visit https://emtecheurope.com/innovators-2022/

Why Plastic?, We The Guinea Pigs

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“We the Guinea Pigs” investigates why we are still constantly – and increasingly – exposed to dangerous chemicals through our plastic use, even though researchers have warned us about the potential adverse health effects for decades. Some of the most cutting edge scientific findings on how plastic harms our health come from Danish researchers Terje Svingen and Hanna Johansson.

A recent study conducted in Denmark has revealed how endocrine disrupting chemicals affect the female reproductive system. It shows that female rats exposed to endocrine disruptors during early development end up with fewer eggs in their ovaries and are at risk of losing their ability to reproduce at an earlier age. For some time researchers have known that plastic has a negative impact on men’s sperm count. Are we involuntary participants in an enormous experiment, threatening the health of millions of people – maybe even mankind as such?

As the use of plastic has gained ground in our lives over the years, there has been an inexplicable increase in a number of diseases and disorders amongst the population. In this film as part of the Why Plastic? series, the BBC meets leading researchers looking into the reasons for these disorders and follow case studies of people suffering from various health conditions thought to be caused by exposure to certain every day materials including plastic. Are these people the victims of unfortunate coincidences – or is there an explanation?

View the episode here.

A pragmatic way forward in chemical safety assessment

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In a recent paper, FREIA partners Terje Svingen (DTU) and Pauliina Damdimopoulou (KI) propose an approach to speed up the development and acceptance of mechanistic descriptions that are used by chemical safety assessors and regulators.

Adverse Outcome Pathways (AOPs) are a way to organise scientific knowledge and describe how a stressor – such as exposure to an endocrine disrupting chemical – can lead to a harmful health effect through a chain of linked events. The use of AOPs is gaining wide acceptance and will help to support chemical safety assessors and regulators.

Yet, only a few AOPs are thoroughly evaluated and endorsed by the Organisation for Economic Co-operation and Development (OECD), which clearly hampers their regulatory use. A major hurdle is the immense amount of work that has to be put into the development of an AOP. “Putting together the information for one key event relationship (the link between two sequential events in an AOP – red.) took me about three months altogether”, explains Eleftheria Panagiotou, PhD student involved in this work.

“We propose to focus more on smaller building blocks and rely more on existing common knowledge”, says lead author Terje Svingen. The approach will make it more attractive for scientists to contribute to AOPs, because in this way, they can focus on their own expertise and don’t have to be an expert on all facets of an AOP from molecular interactions to health effects.

Moreover, a description of a smaller AOP building block makes an excellent paper to be submitted for peer-review. Besides the scientific merit, publishing the building blocks has the added advantage that external peer-reviewers have already critically evaluated the information. This may stimulate faster endorsement of AOPs by the OECD. “It is our hope that our proposed approach will increase the pace at which the AOP knowledge base is populated with endorsed AOPs, which will certainly improve chemical safety assessment processes.”, according to the authors of this paper.

Reference

Terje Svingen, Daniel L. Villeneuve, Dries Knapen, Eleftheria Maria Panagiotou, Monica Kam Draskau, Pauliina Damdimopoulou, Jason M O’Brien. A pragmatic approach to Adverse Outcome Pathway (AOP) development and evaluation. Toxicological Sciences, kfab113, https://doi.org/10.1093/toxsci/kfab113 Published: 17 September 2021

2nd Annual EDC Forum report and recordings now available

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The Second Annual Forum on Endocrine Disruptors took place virtually on 17-18 December 2020. A full report of the conference and the conference recordings are now available.

Read and listen how FREIA coordinator Majorie van Duursen presented challenges and opportunities to identify EDCs that are toxic to female reproduction.

The objective of the Second Annual Forum is to present the actions on endocrine disruptors in the Chemicals Strategy for Sustainability, published as annex to this Strategy, on which the actions are based. In addition, this forum will serve as a platform for policy makers and stakeholders to discuss follow-up actions. Finally, recent developments on endocrine disruptors (research projects funded, European initiatives…) were discussed.

Book review: “Count Down – How our modern world is threatening sperm counts, altering male and female reproductive health, and imperiling the future of the human race” by Dr. Shanna Swan

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Renowned epidemiologist Dr. Shanna Swan is releasing a new book alerting about the threats posed by hormone disrupting chemicals and our modern environment that are imperiling reproductive health, fertility, and the fate of humankind. Building on more than 25 years of research on the associations between exposure to environmental pollutants and health effects, “Count Down – How our modern world is threatening sperm counts, altering male and female reproductive development and imperiling the future of the human race” is a clarion call for more protective public policies and changes in our modern way or living. 

Count Down paints a bleak but important picture about how chemicals in our environment and unhealthy lifestyle practices are disrupting our hormonal balance and causing varying degrees of reproductive havoc. These trends are contributing to the current decline in sperm count, harm fertility, and are leading to long-term and cross-generational health problems even after one has left the reproductive years.

Her 2017 publication of a meta-analysis, which grabbed media attention across the world, found that among men from North America, Europe and Australia, sperm concentration had declined more than 50% in less than 40 years [3]. Dr. Swan already presented EU policy-makers with epidemiological evidence about the impacts of endocrine disrupting chemicals (EDCs) on human health in 2012 – nearly a decade ago [4]. Despite the European Union taking steps to create safe and toxic-free environments, to date these findings have yet to be translated into tangible and health-protective change to reverse current trends.

While associations between exposure to endocrine disrupting chemicals (EDCs) and adverse reproductive health outcomes are increasingly well-documented, few research projects are currently addressing them. The FREIA project – Female Reproductive toxicity of EDCs: a human evidence-based screening and Identification Approach – has started exploring just how endocrine disrupting chemicals (EDCs) affect female reproductive health, and aims at developing test methods to identify EDCs that do so [5]. Elsewhere, the ATHLETE project is aiming to better understand how the environment can impact human health, from pregnancy to adolescence, by studying the human exposome [6]. Meanwhile health groups like the Health and Environment Alliance (HEAL) and federations of professionals such as the Federation of Gynecology and Obstetrics (FIGO) are spreading more awareness around exposure to toxic chemicals during and after pregnancy, and other vulnerable life stages [7].

Count Down: How our modern world is threatening sperm counts, altering male and female reproductive development and imperiling the future of the human race is a wake-up call and a must-read for anyone concerned about the future of our collective environmental health. The book features infographics that are available upon demand, including the infographic ‘Low Doses Matter’ published by TEDX – The Endocrine Disruption Exchange and HEAL in 2019 [8].

This article is re-posted from the HEAL website. View the original post here.

Notes to editor:

  1. “Count Down – How our modern world is threatening sperm counts, altering male and female reproductive development and imperiling the future of the human race”: https://www.shannaswan.com/countdown
  2. Dr. Swan will present her new book during a webinar hosted by the Collaborative on Health and the Environment’s EDC Strategies Partnership on February 23rd, 1PM US Eastern / 7PM Central European time:  https://www.healthandenvironment.org/webinars/96557
  3. Meta-analysis finds that among men from North America, Europe and Australia, sperm concentrations has declined more than 50% in less than 40 years (2017) https://www.env-health.org/etiam-posuere-ipsum-mi-2-2-2/
  4. https://www.env-health.org/2012-04-12_summary-of-swan-points_final/
  5. The Female Reproductive Toxicity of EDCs Project – A Human Evidence-Based Screening and Identification Approach (FREIA) aims to improve the identification of chemicals that affect women’s health via disruption of the hormone system. HEAL is one of 11 partners of the FREIA project: https://www.env-health.org/freia-female-reproductive-toxicity-of-edcs/
  6. The ATHLETE project is a European-funded research project that aims to better understand and prevent health effects of numerous environmental hazards and their mixtures, starting from the earliest stages of life. ATHLETE brings together 22 partners, including HEAL: https://athleteproject.eu/
  7. Infographic: ‘10 tips to avoid toxic chemicals during and after pregnancy’ by FIGO, UCSF and HEAL https://www.env-health.org/figo-ucsf-and-heal-share-10-tips-to-avoid-toxic-chemicals-during-and-after-pregnancy/For further examples of HEAL’s infographics about health-harming chemicals, please visit our joint project with the Belgian Mutualités Libres: https://www.env-health.org/mutualites-libres-and-heal-launch-infographic-illustrating-10-tips-to-avoid-endocrine-disruptors-in-and-around-your-home/
  8. Infographic: ‘Low Doses Matter – Everyday exposures to EDCs contribute to modern health epidemics’ by TEDX – The Endocrine Disruption Exchange and the Health and Environment Alliance (HEAL) https://www.env-health.org/infographic-low-doses-matter/

Join the second FREIA webinar

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EDC IDENTIFICATION: HOW DOES IT WORK?

27 October 2020, 15PM in Brussels.

In 2018, the European Commission adopted criteria to assess whether a biocide or pesticide is an endocrine disruptor. A guidance document was written on how to do this in practice. FREIA partner Julie Boberg (Technical University of Denmark) will explain the process of ED identification, using butylparaben as an example. 

Butylparaben is often used in cosmetics to prevent microbial growth. It is on the candidate list of substances of very high concern of the European Chemicals Agency for its endocrine disrupting properties.

Not only will Dr Boberg show that butylparaben has more negative effects on reproduction than previously thought. It is also a great example that current criteria and EDC identification tools may also be suitable for other chemical regulations.

This webinar is organised by the FREIA project, with support from the Health and Environment Alliance (HEAL). Participation is free. For more details, please contact info@freiaproject.eu

Participation is free. You can register here.

A new FREIA newsletter is out

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The October 2020 FREIA newsletter is released today. We are proud to share some of our research updates, recently published papers, future activities, and introduce you to our talented researcher Hanna Johansson.

Despite the covid-19 pandemic, the FREIA team has done a great job to continue working towards the FREIA goal: provide better test methods for identification of EDCs harmful for female reproductive health.

We warmly invite you to read our latest newsletter or subscribe to future newsletters at www.freiaproject.eu/subscribe

FIGO, UCSF and HEAL share 10 tips to avoid toxic chemicals during and after pregnancy

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The Federation of Gynecology and Obstetrics (FIGO), the University of California – San Francisco (UCSF) and the Health and Environment Alliance (HEAL) have launched  easy-to-use infographics for obstetricians, gynecologists and health groups to create awareness around toxic chemicals and pregnancy in a one-week social media campaign.

Exposure to toxic chemicals before, during and after pregnancy jeopardizes women’s health. The infographics launched today (in English, French, German and Spanish) illustrates 10 tips that women can use for individual lifestyle and routine changes in efforts to avoid health-harming substances, as well as advice for policymakers.

You can download the infographics here on the HEAL website.