It is generally agreed that Cd uptake and accumulation are the first steps in an effector pathway leading to a biological or toxic response, but the relationship between the amount of Cd bound and tissue sensitivity or responsiveness to Cd is still debated. The problem is complicated by Cd induction of factors like MT. MT has been variously reported to reduce, enhance, or have no role in susceptibility to metal toxicity. Initial results in sharks indicate that a single injection of CdCl2 increases the percentage of cysts with apoptotic germ cells in PrM stages where accumulation is maximal. Also, data in this report show that MT-like binding activity increases to a greater extent in GZ and PrM than in later stages.
The complete lack of responsiveness to MT induction by Cd in M stages may be due to a general shutdown of transcription that is known to occur in spermatocytes in rodents. High levels of type I and II Mt mRNA have been localized in germ cells in mouse testis but, in contrast to the stage-related pattern of MT-like protein in sharks, mRNA levels are highest in spermatocytes and round spermatids. flovent inhaler
Although further work is required to characterize the in-tratesticular Cd-binding mechanism and to determine its localization in germ cells or Sertoli cells, we conclude that the shark testis model has utility for stage-by-stage analysis of spermatotoxicant accumulation and effect.