(ii) Dynamic and less well-defined tolerance mechanisms that control autoreactive lymphocytes. More than 40 years ago,

Johnson & Setchel cannulated the rete testes of rams and collected testicular fluid for analysis, noting the very low concentrations of proteins, including immunoglobulins, when compared with serum and lymph.53 They proposed the presence of a blood–testis permeability barrier around the seminiferous tubules. Initially, this was felt to be at the level of the myoid cells surrounding the base of the tubule. Subsequently, Dym & Fawcett54 studied the tight junctions in the seminiferous epithelium and the peritubular contractile layer at high magnification in rats, investigating selleck kinase inhibitor the permeability of these junctions to lanthanum nitrate, a very small electron-opaque tracer used in testing the

patency of intracellular clefts. They demonstrated that the blood–testis barrier existed at the level of tight junctions between CCI-779 Sertoli cells, what created a basal compartment containing lanthanum, separated from an adluminal compartment that did not. Cell surface interactions in the seminiferous epithelium are very dynamic. This epithelium consists of columnar Sertoli cells, along whose surface different generations of germ cells progress toward the tubular lumen while undergoing spermatogenic differentiation.3,4 The Sertoli cell lateral membrane is involved in dynamic contact with the germ cells, as well as in connecting adjacent Sertoli cells to each other by a belt of occluding junctions that provide structural integrity to the BTB. The domains of the Sertoli cell involved in anchoring late spermatids as well as those involved in inter-Sertoli junctional contacts in which the Sertoli cell membrane is paralleled by a thick bundle of actin filaments,

the so-called ectoplasmic specialization (ES).4,10 The BTB physically divides the seminiferous epithelium into basal C1GALT1 and apical (or adluminal) compartments. Besides its function as an immunologic barrier to segregate post-meiotic germ cell antigens from the systemic circulation, it creates a microenvironment for germ cell development and confers cell polarity. During spermatogenesis, the BTB must physically disassemble permitting the passage of preleptotene and leptotene spermatocytes. Studies have shown that this dynamic process is regulated by transforming growth factor-beta 3 (TGF-beta-3) and tumor necrosis factor-alpha.55 Antisperm antibodies (ASA) are detected in approximately 70% of men who have undergone vasectomy.56 These antibodies have also been associated with obstructive azoospermia secondary to cystic fibrosis and with unilateral or bilateral congenital absence of the vans deferens.57 Autoimmunity to sperm can also occur following testicular trauma or following mumps orchitis, which may occur in post-pubertal men but is rare before puberty.