DESCRIPTION (provided by applicant): Male reproductive disorders have become an important public-health issue during recent decades: The incidence of testicular cancer has increased and semen quality has decreased, and the incidences of cryptorchidism and hypospadias appear to have increased in certain regions. These conditions are thought to reflect an underlying entity called the testicular dysgenesis syndrome (TDS), with a common origin in fetal life. TDS appears also to be related to other adverse effects, such as decreased birth sex ratios. Although the etiology is uncertain, endocrine disruption is suspected, perhaps due to persistent organochlorine pollutants. Research in this area has been impeded by the relative rarity of some pathologies and because functional assessment of male reproduction is feasible only at adult age, i.e., many years after the initial toxic exposures. We have chosen to carry out a study in the Faroe Islands north of Scotland, where the residents have an increased exposure to suspected endocrine disrupters from traditional marine food, which may include meat and blubber from the pilot whale. Wide exposure intervals are known to exist and appear independent of confounders in this rather homogeneous community. In Faroese adults, an estimate of prenatal exposure levels can be obtained from the mother's dietary habits and current serum concentration of persistent organochlorine substances. The study will therefore examine reproductive outcomes thought to be associated with endocrine disruption and the TDS. These will include measures of semen quality, ratio of X/Y chromosome-bearing sperm, chromatin stability of the sperm, sex ratio of births, and waiting time to pregnancy. The study will include 400 pregnant couples whose mothers are also invited to participate. Because the men of the pregnant couples constitute a selected population (about 250 are expected to provide a semen sample), we will also examine semen quality parameters in 250 young men from the general population (aged 20-24 years) as well as their exposures. This study therefore aims at providing evidence whether increased exposure to endocrine disrupters, whether from postnatal sources or from prenatal exposure caused by maternal seafood consumption, is associated with reproductive abnormalities in both men and women. Decreased sperm quality, decreased fertility, and decreased sex ratio are reproductive outcomes of substantial public health interest. Current evidence already suggests that these pathologies may already affect many populations, and the present proposal aims at identifying whether persistent organochlorine pollutants contribute to these abnormalities.