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General Information
Lifestyle and genetic predisposition are considered to be the main determinants of non-communicable diseases in humans. Today, however, there is
increasing
evidence from studies in several distinct human populations in Europe and elsewhere, that many disorders occurring in adult life date back to influences of the intra-uterine environment during prenatal time. Examples of illnesses for which there is evidence of foetal origin are hypertension, coronary heart disease, diabetes and neurological disorders. In addition, behavioural disorders in childhood and adolescent life may also be programmed in the prenatal period. Since it is generally accepted that a multitude of pre- and postnatal influences are involved in pathophysiological processes that predispose individuals to such diseases, it is plausible to propose that there are factors triggering foetal development, thus amplifying or minimising certain long-term processes. One identified trigger is hormonal disturbance such as high glucocorticoid exposure during pregnancy. However, most of the respective studies in humans have been restricted to either epidemiological or some physiological measurements that in sum cannot explain the cause and basic mechanisms underlying the pathophysiological processes. Whilst many have argued on the basis of conventional rodent and ruminant animal models to explain the links between prenatal events and the commonest human disorders, none has shown strict relevance to human biology.
Understanding how such prenatal programming works, and knowledge of underlying pathophysiological changes provide one of the most exciting challenges
in contemporary biomedical research. Since ethical constraints determine that
mechanistic observations can only remain indirect in humans, more profound studies need to be conducted in a non-human primate, a species closely related to humans. Therefore, the EUPEAH programme proposes to investigate in the marmoset monkey, a non-human primate species, the evidence underpinning premature over-exposure to glucocorticoids as a key trigger of adult disease programming.
The EUPEAH
consortium provides the infrastructure to breed and house marmoset monkeys and to perform multidisciplinary and strongly interconnected studies in a longitudinal approach by sharing biological material, technology, knowledge and data between the partners. The establishment of a European non-human primate bank (EPTB) for tissues and body fluids harmonise resource collection and distribution between diverse research facilities, preventing duplicate collections across Europe, reducing the number of experimental animals thus contributing to animal welfare.
Besides state of the art animal facilities, the consortium has methods for ultrasound
examination of pregnancies, for measuring the endocrine and metabolic status in plasma and urine samples, for behavioural analysis, for telemetry to measure blood pressure, non-invasive brain imaging (MRI), computer-assisted tomography (CT) to measure bone development as well as body fat deposits. Furthermore, the following techniques and respective equipment are also set up in the laboratories of the EUPEAH partners: immunohistochemistry and a wide spectrum of cell and molecular biological methods including proteomics (quantitative PCR, 2D-SDS-PAGE, MALDI-TOF, LC-MS/MS) to quantify the impact of prenatal dexamethasone treatment on various body systems.
To unravel gene expression
profiles of different organs and allow the delineation of complex biological pathways a marmoset-specific cDNA microarray (EUMAMA) will be generated. This way, the optimum exploitation of technical expertise and scientific knowledge of the various groups is guaranteed, thereby increasing the efficiency and performance of the individual partner institutions.
The need for non-human primates in biomedical research was defined by a statement of the Scientific Steering Committee of the European Commission and adopted at its
meeting of 4-5 April 2002. Whether non-human primates are used for research, will need to be decided upon on a case-by-case basis, and following a careful assessment, which takes into account the justification, the
possible existence of alternatives, ethical considerations and the problems that could result from not using the non-human primates. However, the Scientific Steering Committee considers that for certain experiments
there are actually no alternatives to the use of non-human primates.
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