Reproductive and Endocrine Toxicology
E.W.P. Wong, ... C.Y. Cheng, in Comprehensive Toxicology, 2010
11.09.2.3.2 Physiological significance of the BTB and its vulnerability to cadmium toxicity
In mammalian testis, BTB anatomically divides the seminiferous epithelium into the basal and the adluminal compartments. During spermatogenesis, preleptotene spermatocytes residing in the basal compartment of the seminiferous epithelium must translocate across the BTB, entering into the adluminal compartment for further development at stage VIII of the epithelial cycle (Russell 1977). Once behind the BTB, spermatocytes continue their differentiation into spermatids and migrate progressively across the epithelium until elongated spermatids reach the luminal edge of the epithelium (de Kretser 1990; de Kretser and Kerr 1988). The fully developed elongated spermatids (spermatozoa) then detach from the epithelium at late stage VIII of the epithelial cycle at spermiation. This event of germ cell movement across the BTB is undoubtedly unique to the testis. It also illustrates that BTB is a highly dynamic structure since it has to open (or restructure) to facilitate germ cell migration while maintaining the barrier function to sequester postmeiotic germ cell antigens behind the BTB from the immune system of the host animal (for reviews, see Byers et al. (1993), de Kretser and Kerr (1988), Dym and Cavicchia (1978), Dym and Fawcett (1970), Pelletier (2001), and Pelletier and Byers (1992)). It is likely that due to the dynamic nature of the BTB, it is being safeguarded by the coexisting TJ and specialized AJ structures basal ES. This is plausibly physiologically necessary, perhaps even essential, to maintain BTB integrity during extensive junction restructuring in the seminiferous epithelium pertinent to spermatogenesis. Yet it is also plausible that because of this unusual feature of the BTB being composed of coexisting AJs and TJs, it makes the BTB more susceptible to cadmium toxicity. For instance, it is known that cadmium mediates its toxic effects primarily on AJ proteins (e.g., E-cadherin) (Prozialeck 2000), perhaps only secondarily on TJ proteins and cytoskeletal elements. But since the BTB is composed of coexisting TJ and AJ proteins and the BTB is adjacent to ECM in close proximity to the interstitium, basal ES proteins (e.g., E-cadherin and integrins) at the BTB are readily exposed to cadmium. As such, BTB is more severely affected by cadmium than microvascular TJ barrier where TJ proteins are restricted to the apical surface which, in turn, seals the underlying AJ network from cadmium.