Dr. Pauliina Damdimopoulou’s group focuses on reproductive toxicology and recently, they have been working on a new technique obtained from Dr. Claus Andersen’s laboratory in Copenhagen. They have been isolating structures from within the ovary called follicles, which consist of supporting and nourishing cells surrounding the growing egg.
The group has successfully modified the technique learned in Copenhagen to isolate follicles from bovine and human ovaries, specifically focusing on an area of tissue called the cortex which contains the most follicles. The next step is culturing follicles for long periods of time, such as several days or weeks, so that the effects of chemical mixtures on egg development and health can be tested. The research will increase our understanding on whether chemicals can affect women’s fertility.
A growing follicle after 5 days of culture. The egg can be seen in the centre of several layers of supporting cells.
For more information on the research team:
The position is linked to EDC-MixRisk project and it is open at the Department of Environmental Science and Analytical Chemistry, Stockholm University. The Postdoctoral Fellow will contribute to the work package that concerns the development of a transparent and systematic risk assessment procedure that can integrate epidemiological and experimental research to facilitate the assessment of risk for EDCs and their mixtures.
Main responsibilities will include:
(1) To perform a risk assessment case study with a single chemical, using the recently proposed SYRINA framework for EDC risk assessment. SYRINA is described here: http://ehjournal.biomedcentral.com/articles/10.1186/s12940-016-0156-6. The case study includes performing all the steps outlined in SYRINA for a selected case chemical. The process will also be presented and discussed with all other scientists involved in the project.
(2) Together with other scientists in EDC-MixRisk, further develop the SYRINA framework to encompass also mixtures.
For more information, click here.
Meet our EDC-MixRisk scientists working behind the scenes. Prof. Chris Gennings shares her insights into the project. She is Professor of Biostatistics at the Icahn School of Medicine at Mount Sinai, NY, USA and her research focuses particularly on the design and statistical analysis methodologies for studies of chemical mixtures.
Hi Chris – What are you researching in EDC-MixRisk?
We are using the SELMA pregnancy cohort data to identify mixtures of endocrine disrupting chemicals (EDCs) measured in early pregnancy that are associated with health effects in each of three health domains for the children: neurodevelopment, metabolism and growth, and sexual development. Our strategy includes evaluation of chemicals across a wide range of chemical classes. Once the sets of ‘bad actors’ are identified, we calculate a ‘typical mixture’ from the SELMA cohort data for each health domain using pharmacokinetic modeling. These mixtures are then constructed and experimentally evaluated across the consortium.
What are the key results so far?
Important results so far include the identification of bad actors that are detected in all or nearly all of the pregnant women in the SELMA cohort. Second, these identified chemicals come from multiple chemical classes, indicating that focusing on single chemical classes may underestimate risk. Further, we have detected health effects from each of the three health domains, indicating the potential comorbidity associated with exposures to EDCs.
What these findings could implicate?
The strategy we use for identifying bad actors is based on the simultaneous evaluation of mixtures of chemicals related to a health effect, i.e., the so-called ‘mixture effect’. An advantage of this strategy is the inference is focused towards detecting the mixture effect and thereby has more power to find it. Single chemical analyses may not indicate statistically significant associations; but combining across components we detect higher signal. The potential consequences are that we may identify that current regulatory guidelines, which generally focus on single chemicals or single chemical classes, are not adequately protective.
The annual Consortium meeting will be organized in Stockholm, 15-17 May 2017. The first day of the meeting will focus on presenting some of the key results of EDC-MixRisk project as well as of EDC-2020 project. Also a workshop on Adverse Outcome Pathways will take place in the context of the meeting. The following days aim at discussing and reviewing the progress of the project and future plans.
Meet our EDC-MixRisk scientists working behind the scenes.
This time Dr. Hannu Kiviranta is in the spotlight: He is head of the Chemicals and Health Unit at the National Institute for Health and Welfare (THL), located in Kuopio, Finland. In EDC-MixRisk Project, Dr. Kiviranta is Work Package Leader in WP3 that focuses on chemical and biological analyses.
Hi Hannu – What is your research group investigating in EDC-MixRisk?
Our task is to measure persistent organic pollutant (PCBs, organochlorine pesticides, and polybrominated flame retardants) in two large European pregnancy cohort, namely SELMA and LIFE Child Study. These results will be utilized to identify critical EDC mixtures which will then be tested in various animal and cell models. In addition, these exposure estimates will be used in traditional epidemiological studies in order to find associations between exposure and health endpoints in focus in EDC-MixRisk Project.
What have you discovered so far?
We have so far analyzed all SELMA cohort serum samples from mothers and these results have been used for determining the next set of critical mixture, Mixture I, to be used by other partners in experimental studies.
What are the potential implications of your findings?
We will have interesting data of the exposure of fetus to persistent organic pollutants in two large birth cohorts and enhance our understanding of the total exposure fetus is facing during sensitive developing stage at early life. If these exposures, both with persistent and non-persistent chemicals, will be associated to those health endpoints studied in EDC-MixRisk (either through mixture studies or in epidemiological studies), the project will provide crucial data for risk assessment and to risk managers to take actions to reduce the exposures in the future.
The overall concept underpinning EDC-MixRisk is that early life exposure to EDC mixtures induces changes in the organism that underlie increased susceptibility to diseases during the entire life span. Three health domains will be addressed in the project: growth and metabolism, neurodevelopment, and sexual development. Furthermore, the project integrates research from three relevant scientific modules: 1) epidemiology, 2) experimental systems and 3) risk assessment and societal impact. In the epidemiological module, mixtures of EDCs are identified, through associations between exposure and health outcomes in the three domains. These mixtures are tested in different experimental systems relevant for the respective health outcomes, whereas the experimental data are integrated into the risk assessment methods developed in module 3.
In contrast to the vast majority of studies that focus on one chemical and one physiological outcome at the time, EDC-MixRisk has developed a multiple-exposure-to-multiple-outcome approach, which mimics the real life exposure situation. Our first results demonstrate that EDC mixtures associated with adverse health outcomes in population based epidemiology evoke relevant molecular and physiological effects in experimental systems in cells and animals, even at low concentrations. This demonstrates the validity of our approach in interacting between epidemiology and experimental toxicology and the need to take mixture effects into account for risk assessment. The major innovative potential of EDC-MixRisk lies within the improved risk assessment methodologies directly linked to the data obtained in the project, and strategies to systematically engage policy-relevant stakeholders. Improved regulatory processes will be important for the general populations globally, for national regulatory agencies and organizations; for chemicals manufacturing industry and down-stream users of these chemicals.
Read the full summary here
The second half-year meeting of the EDC-MixRisk Project Steering Committee was organized in Athens, 1-2 December 2016. The meeting provided an overview of the progress on various tasks and ongoing activities within the project.
The discussions of the meeting focused mainly on creating the strategy for the next relevant mixture of chemicals to be tested in the different health domains; the risk assessment procedures of mixtures; as well as planning of a White Paper based on the approach, results and outcomes of the project. Also, the scientific progress in the field was discussed.
The meeting provided an excellent forum to address multidisciplinary aspects, information flow and the overall strategy of the project. It was concluded that the project is on track and a lot of interesting and useful data is being produced.
EDC-MixRisk scientists have contributed to another open letter to the EU Commission about the proposed criteria for classification of endocrine disrupting chemicals (EDCs). The letter is a response to the EC’s recently-published revised draft criteria.
While the redrafted criteria have attempted to address a number of concerns, the changes are insufficient and the proposed criteria are considered not fit for purpose.
Click here to read the letter.
The open letter was originally published by Paul Whaley (16 Nov 2016) on http://policyfromscience.com/another-open-letter-to-the-eu-commission-about-the-edc-criteria/
The work performed in EDC-MixRisk is vital to expand our knowledge on mixtures of endocrine disrupting chemicals. Here you will meet the scientist behind the research and hear their story on what they are doing and why it is important.
Vice-Coordinator of the project, Dr. Joëlle Rüegg from Swetox/Karolinska Institutet reveals some preliminary results of experimental studies.
Hi Joëlle – What is the aim of your experiments?
The aim of our experiments is to investigate if Mixture G, a mixture of EDCs that is associated with low birth weight in the SELMA children, changes features in mesenchymal stem cells so that they are more prone to differentiate towards fat cells (adipogenesis) than towards bone cells.
What have you discovered so far?
In our initial experiments, we have investigated the effects of different doses of Mixture G on adipogenesis of these cells. We found that even low doses of the mixture (10 times higher than the mean concentration found in the SELMA mothers) increased adipogenesis within weeks of exposure. We are now in the process of confirming these results. Further, we are investigating which genes are affected by the mixture and could be responsible for this increase in adipogenesis.
What these findings could implicate?
Our findings indicate that an EDC-mixture that is associated with low birth weight (which is, in turn, indicative for metabolic problems) changes features of stem cells so that they can more easily become fat cells. This could implicate that the higher exposed children are more prone to develop obesity later on in life.
EDC-MixRisk Project Partner, Prof. Christina Rudén (Stockholm University) will be discussing the SYRINA framework at an upcoming workshop “Association or causation in miasmas and mixtures: Current reflections on Bradford Hill’s 1965 contribution to Public Health”. The meeting will be organized in London, Royal Society of Medicine 13-14 October 2016.
The title of Prof. Rudén’s speech will be: Bradford Hill and evaluating evidence for action on endocrine disrupting chemicals: SYRINA.
The key messages of her speech point to the need of novel approaches to be used in risk assessment of endocrine disrupting chemicals. The SYRINA framework adds structure and transparency in the assessment process. It also encourages inclusion of all data – both regulatory studies and academic research, and allows integration of data from different streams of evidence to support conclusions. The method has been developed in international cooperation, with a main contribution from the EDC-MixRisk project.
The workshop is organized by the Epidemiology & Public Health Section of RSM in partnership with Brunel University London, the London School of Hygiene and Tropical Medicine and Imperial College London. For more information about the event: https://www.rsm.ac.uk/events/eph01