REEF (Reproductive effects of environmental chemicals in females)
DEER (Developmental effects of environment on reproductive health): focus on male reproductive health problems.
CONTAMED (Contaminant mixtures and human reproductive health - novel strategies for health impact and risk assessment of endocrine disrupters)Focused on the development of biomarkers for combined exposures of chemicals and long-term delayed effects of chemical cocktails.
CLEAR (Climate change, environmental contaminants and reproductive health)
There is a large body of evidence that when a developing foetus is exposed to environmental chemicals (ECs), its future reproductive potential may well be reduced. These ECs include endocrine disrupting compounds (EDCs), and their adverse effects are seen in wildlife, domestic species and humans. Currently scientists and doctors think that such exposure to ECs is part of the mechanism increasing the rates of reproductive defects and infertility in males and females. Just one example is the 2% annual increase in EU breast cancer rates.
Studies on a wide range of ECs, including the plasticisers, phthalates, and many other chemicals (e.g. PCBs, BPA and dioxins), show that the female reproductive tract is sensitive to damaging effects of chemicals, often in a manner different to the male. In the past, many studies have focused on single or small numbers of ECs, on short-lived rodent species, and have used high doses of the chemicals. These patterns of exposure to chemicals is completely different from how humans are exposed to ECs and research to better understand the risks posed by man-made chemicals must tackle this difficult issue.
The sheep, exposed to sewage sludge treated pastures, provides a model of real-life exposure to a broad range of ECs at low/environmental concentrations. Sheep are long-lived and have many reproductive similarities with humans. Therefore REEF will utilize this model, as well as the mouse, in order to clarify links between exposure of the female during fetal development, her reproductive capacity as an adult and the extent to which damage is passed on to her own young.
How will REEF address these problems?
The REEF partnership believes that the issue of environmental factors and their possible role in the deterioration of human reproductive health in Europe demands research into specific damage of the female. REEF will analyze tissues from sheep and mouse models of exposure to “real-life” very complex mixtures of ECs, and also to focused combinations of ECs, and then directly relate the outcomes to the human fetal ovary . The project’s aims are:
It is widely accepted that fetal events can predispose an individual to develop certain health disorders in adulthood; indeed, the commonest disorders of European and Western adults today (obesity, type 2 diabetes, cardiovascular disease), which are increasing progressively in incidence, are well-established to have prenatal determinants.
Equally, it is increasingly clear that the commonest disorders of male reproductive health in newborn (cryptorchidism, hypospadias) and young adult (low sperm counts, testis germ cell cancer) human males may also be caused by adverse events in fetal (and perhaps neonatal) life. These reproductive disorders are thought to comprise a testicular dysgenesis syndrome (TDS), which arises because of a cascade of changes triggered by maldevelopment and malfunction of the foetal testis. The incidence of TDS disorders appears to be increasing in Europe.
Several pieces of evidence suggest that common environmental chemicals, probably acting together in mixtures or in combination with other factors (genetic, lifestyle) could contribute causally to TDS. However, there are numerous obstacles to proving this scientifically, such as the long latency (up to 40 years) between cause (in fetal life) and health consequence, coupled with inherent difficulties in evaluating human fetal exposure to complex chemical mixtures; assessing interactions between chemical exposures and other factors adds greater complexity.
How will DEER address these problems?
In order to circumvent the above-mentioned obstacles we will in DEER take advantage of existing human birth cohorts/samples with their associated chemical exposure analyses. Established animal and in vitro models will be used to improve our understanding of fetal testis development and function and its relationship to male reproductive development. The complexity of real-life chemical exposures will be tackled by new bioinformatics approaches for assessing associations between real-life exposure scenarios and effects in humans. More specifically:
Of considerable concern in Europe is a decline in male semen quality and an associated decrease in fertility. There have also been reports of increased incidence of physical defects of male reproductive organs in newborns. These pertubations in reproductive health, as well as increased incidence of hormone-dependent cancers, may be due to disruption of hormonal signaling in the womb.
Environmental chemicals may contribute to disruption of signaling pathways in the fetus and thereby be involved in the causation of these disorders. At present, individual substances cannot be shown to contribute to adverse effects at relevant exposure levels, however, people are typically exposed to multiple chemicals simultaneously.
There are indications that combinations of chemicals may play a cumulative role, for example, associations between malformations in boys and estrogenic load in mothers’ placentas have been reported. Adverse health effects in boys were also linked to widely used plasticizers, pesticides and other environmental chemicals found in mothers’ milk and urine. However, more information is needed to substantiate these findings.
How will CONTAMED address these problems?
The CONTAMED partnership believes that the issue of environmental factors and their possible role in the deterioration of human reproductive health in Europe cannot be resolved without considering combined exposures. CONTAMED will analyze human tissue specimens from existing mother-child cohorts, conduct experimental studies in animals and laboratory assays, and will use cutting-edge chemical analytical techniques. The project’s aims are:
The research project investigates the possible impact of global climate change on reproductive health in one Arctic and two European populations. The key questions to be addressed are, firstly, how may climate change influence human exposure to widespread environmental contaminants and, secondly, how may contaminants impact occurrence of reproductive disorders as sensitive indicators of health?
To provide affirmative answers to these questions the proposal will as a first step identify and describe mechanisms by which a changing climate may affect the exposure of Arctic and other human populations to contaminants through change in chemical use and emissions, delivery to the arctic ecosystem as well as processing within the arctic physical environment and human food chain. This work relies on modelling of existing data.
Secondly, the project will expand the existing knowledge database on human exposure to polybrominated biphenylethers, perfluorinated surfactants and phthalates by analyses of 1000 biobanked serum samples collected in a EU FP5 project.
Thirdly, the project will increase the limited knowledge on links between human exposure to contaminants and reproductive health. This work relies on a large existing parent-child-cohort, where a follow-up survey provides new data that are fed into risk assessment. Furthermore we will perform reviews of experimental and epidemiological literature to identify critical reproductive effects and exposure-response data for selected compounds as input to the risk assessment.
Finally the project will integrate data on climate-induced changes in contaminant mobility and distribution and links between contaminant exposure and reproductive health into a risk evaluation providing insight into possible future risk scenarios related to global climate change.
The project draws upon a network of experts in climate modelling and in experimental, epidemiological and risk assessment methodologies and builds upon