"Impact of endocrine disruptors on primate spermatogenesis"

The objective is to systematically examine, by integrating physiological, cellular, and molecular approaches, the impact of endocrine disruptors or modulators on pubertal testicular development using the juvenile non-human primate (rhesus monkey) model. Current thinking is that exposure to endocrine disruptors or modulators prevalent in the environment accounts, in part, for an increase in the development of reproductive disorders in boys and a significant decline in sperm count in men. The putative, adverse effects of endocrine disruptors on spermatogenesis may manifest indirectly by interfering along the hypothalamic-pituitary-testicular axis or directly at the level of the testis to compromise reproductive functions. To address the direct testicular effects of endocrine disruptors during puberty, prepubertal primate 'testicular clamp' preparation is used as an experimental model, and, in the presence of endocrine disruptors or modulators, 'testicular puberty' is induced by stimulating the testes of the immature monkey in a physiological manner with exogenous recombinant gonadotropins (FSH and LH). The focus of research is to identify in the primate testis the cell types (Sertoli, Leydig, and stem germ cells) and their specific endocrine/paracrine functions that are vulnerable to actions of endocrine disruptors during puberty. In addition, in collaboration with other members of the University of Pittsburgh Center for Research in Reproductive Physiology, alterations in the cell signaling mechanisms and functional integrity of genes due to endocrine disruption will be characterized.