Objectif Temporal and regional trends of malignant and reproductive disorders have renewed interest in environmental pollutants. Biopersistent organochlorines (POC) in food are an important source of environmental exposure to xenohormones. The objective of this proposal is to characterize the impact of dietary POCs on human fertility and to provide evidence in support of or against the environmental hormone hypothesis. Inuit people in Greenland, Swedish fishermen's families and population samples from Poland and Ukraine are selected for studies of time taken to conceive, semen quality and endocrine disruption. The study includes people with documented body burdens of POCs ranking among the highest in the world. Uniform study design and centralized laboratory analyses allow for pooled epidemiologic analyses.Couple fertility is measured by time to pregnancy (TTP). TTP data are collected by interview with the female partner. The Swedish TTP study addresses fishermen's families at the Baltic coastline (averagely high POC levels) and the Western coastline (averagely low POC levels). The TTP studies in Greenland, Poland and Ukraine enroll pregnant women referred to hospital for delivery. The women are included to ensure a balanced distribution of high and low level exposed couples (sea mammal diet versus European diet in Greenland; POC polluted regions versus other regions in Ukraine) In Warsaw, the POC levels are in range with most European levels and here the inference is based upon the natural contrast within the population. At least 600 pregnant women are enrolled at each site giving a total study size of some 2400 couples.Semen and neonatal studies are conducted in subsets of respectively 800 men and 100 male babies selected to provide maximal contrast of exposure.A long-term measure of POC exposure is obtained by determination of the PCB congener CB-153 in plasma (some 3000 measurements). A direct indication of the total non-endogenous estrogenic and androgenic activity of blood is measured in 400 men by in-vitro cell culture bioassays using gene constructs.In addition to standard measures of semen quantity and quality, we analyse the sperm chromatin structure - which is a strong and independent measure of male fertility -, markers of germ cell apoptosis and the ratio of sperm sex chromosomes. Apoptosis and the germ cell sex chromosome ratio are believed to be influenced of sex hormones and gonadotropins. Therefore, xeno hormones might also influence these endpoints. Finally, the reproductive hormones including inhibin B are measured in peripheral blood in 800 men and 100 newborns to indicate disruption of the hormonal regulation.We set out to corroborate or reject that high dietary intake of POC causes delayed time to conception because of impaired spermatogenesis due to disturbed gonadal development in prenatal life. The project will contribute scientific knowledge as basis for appropriate assessment and management of risk related to consumption of POC contaminated diet and provide strong evidence in support of or against the hormonal disruption hypothesis.This proposal is linked to a Shared Cost RTD proposal which was selected by the EU Commission for contract negotiations (INUENDO - QLRT-2000-00202) in June 2001, but the Ukranian contribution can not be funded by EU. This INTAS proposal is to raise funding to carry out the Ukranian studies while the funding for the epidemiologic studies in Greenland, Sweden and Poland as well as expenses to coordination, centralized analyses of biological samples in Sweden, Denmark and Italy (including Ukranian samples) and data analyses are provided by EU. Programme(s) IC-INTAS - International Association for the promotion of cooperation with scientists from the independent states of the former Soviet Union (INTAS), 1993- Thème(s) 5 - Earth Sciences, Environment, Energy POLL - POLL : Polluted Environment Appel à propositions Data not available Régime de financement Data not available Coordinateur UniversityHospital of Aarhus Contribution de l’UE Aucune donnée Adresse Noerrebrogade 44 8000 ?rhus Danemark Voir sur la carte Coût total Aucune donnée Participants (6) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire Ente Per Le Noueve Technologie, l'Energia e l'ambiente Italie Contribution de l’UE Aucune donnée Adresse Cr Casaccia Via Anguillarese 00060 Rome Voir sur la carte Coût total Aucune donnée Karkhiv Hospital University Ukraine Contribution de l’UE Aucune donnée Adresse Lenin pr. 4 61022 Kharkov Voir sur la carte Coût total Aucune donnée Kharkov Regional State Administration Ukraine Contribution de l’UE Aucune donnée Adresse Moscowsky 195 61037 Kharkov Voir sur la carte Coût total Aucune donnée National Institute of Hygiene Pologne Contribution de l’UE Aucune donnée Adresse Chocimska 24 00-791 Warsaw Voir sur la carte Coût total Aucune donnée Universita di Modena Italie Contribution de l’UE Aucune donnée Adresse Via campi 213/D 41100 Modena Voir sur la carte Coût total Aucune donnée University of Lund Suède Contribution de l’UE Aucune donnée Adresse Lund University Hospital 22185 Lund Voir sur la carte Coût total Aucune donnée
