Hormones and testis development and the possible adverse effects of environmental chemicals

Abstract

Development of a fetus into a phenotypic male depends, first, on testis formation and second, on hormone production by the fetal testis. Disorders of testicular hormone production or action can lead in severe cases to phenotypic abnormalities or can predispose towards impaired reproductive health. Evidence for deteriorating human male reproductive health, especially an increase in testicular cancer, points to disturbed (hormonal) development of the fetal testis. By comparison of testicular dysgenesis in humans and exposure to certain phthalates in fetal rats, the similarities in outcomes and testicular cell-cell disruption are highlighted as are the pathways via which oestrogenic and (especially) anti-androgenic environmental chemicals might act to induce such changes. The susceptibility of sperm production in adulthood to 'hormonal' disruption in fetal and neonatal life is also discussed. Though it is concluded that no direct evidence links human exposure to environmental chemicals and male reproductive disorders that stem from disturbed testis development, this is based mainly on lack of information. Using the example of phthalates, for which new data have emerged, it is argued that until the appropriate in vivo studies are undertaken, the safety of hormonally active environmental chemicals, especially in mixtures, will continue to give cause for concern as far as testicular development is concerned.