SENSITIVITY OF SERTOLI AND LEYDIG-CELLS TO XENOBIOTICS IN IN-VITRO MODELS

Different chemicals are known to cause testicular damage in the human male and experimental animals. However, the ability to assess the pote ntial and mechanism of action leading to chemically-induced damage in men has been hampered by a lack of good predictive models. Although ma ny of these chemicals were found to impair reproductive capacity in va rious laboratory animals, only some have caused reproductive damage in men. Mammalian spermatogenesis takes places within the avascular semi niferous tubules of the testis. Specialized tight junctions, which for m between adjacent Sertoli cells at the time of puberty, divide the tu bular space into the basal and adluminal compartments, and create a '' blood-testis'' barrier that restricts passage of substances and ions f rom the circulation. Thus, the completion of meiosis and post-meiotic germ cell differentiation, which take place in the adluminal compartme nt, are isolated from circulating substances unable to cross the blood -testis barrier. It seems feasible, therefore, that damage to the germ cells induced by testicular toxicants may be mediated through other c ells in the testis such as the Sertoli, peritubular, or Leydig cells. A recently developed two-compartment system for culture of testicular cells can simulate, to some degree, the normal physiologic conditions. In principle, Sertoli cells isolated from mammalian testes are cultur ed on a permeable support (that is millipore filter) between two fluid compartments. They form a highly polarized epithelial layer with char acteristic tight junctions that restrict the passage of substances bet ween the two compartments, in analogy to the blood-testis barrier. We believe this system provides an excellent in vitro model for determini ng the ability of chemicals to: a) alter the permeability of the blood -testis barrier, b) impair the secretory function of Sertoli cells, or c) affect their viability, all of which could indirectly affect the g erm cells. We have utilized this system for examining the effects of c admium chloride (CdCl2) and other toxic substances known to affect the testis. The Leydig cell toxicity was investigated in testicular perfu sion system or cultures of isolated Leydig cells.