Blood testis barrier

No adverse effects were noted in the testes. The results of this study indicate that lead affected spermatozoa after release from the germinal epithelium which was possibly protected from the effects of lead by the blood-testes barrier (Barratt et al. 1989). 

To provide a barrier between the tubules and the blood the blood-testes barrier. 

The blood-testes barrier separates two parts of the seminiferous tubules, the part in which the spermatozoa are produced from the outer part which provides the blood supply. It has two functions (i) it prevents spermatozoa leaking into the blood or lymph, since proteins on the surface could act as antigens (ii) it maintains the distinct composition of fluid inside the tubules, which is necessary for spermatogenesis. 

It is sometimes possible to get an indication of how widely the parent compound may distribute in the body from the available physico-chemical data. The sites to which the parent compound distributes (pattern of distribution) once it has entered the systemic circulation are likely to be similar for all routes of administration. In general, substances and their metabohtes that readUy diffuse across membranes wUl distribute throughout the body and may be able to cross the blood-brain and blood-testes barriers, although the concentrations within the brain or testes may be lower than that in the plasma. The rate at which highly water-soluble molecules distribute may be hmited by the rate at which they cross cell membranes and access of such substances to the central nervous system (CNS) or testes is likely to be restricted (though not entirely prevented) by the blood-brain and blood-testes barriers. 

The actions of P-gp located on the cell surface that act to restrict substrate access and to enhance elimination via efflux directed from cytoplasm to extracellular milieu are the most widely studied and understood. The remainder of this section will focus on the ramifications of the P-gp activity at the cell membrane level to disposition, which has been shown to be particularly relevant in barrier tissues such as the intestine, BBB, and blood-testes barrier, and in cells of eliminating organs such as hepatocytes and renal tubule cells. 

Sertoli cells are epithelial cells that line the seminiferous tubules of the testes. At their basal aspects, these cells form the basement membrane and tight junctions that make up the highly selective blood-testes barrier, which normally prevents entry of immune cells into the lumen. 

Zinc fed to adult male rats at 500.0 mg/kg diet for 3 weeks or longer negatively impacts the testes and other male accessory organs effects are a direct result of zinc cytotoxicity from transfer across the blood-testes barrier. Elevated dietary zinc also depresses bone calcium levels and increases fecal calcium loss in rats. Inaeases in semm zinc levels of rats after acute zinc overload is mainly due to increases in the zinc bound to the albumin fraction. 

P-glycoprotein (P-gp), also known as ABCBl, or multi-drug resistance protein 1 (MDRl), is a multi-drug efflux pump (a protein that removes drugs and related compounds from cells) that can move a wide variety of compounds across cellular membranes. P-gp is concentrated in the excretory tissues (liver and kidney) and in barrier tissues (intestines, blood-brain barrier, placental barrier, blood-testes barrier,... 

Setchell BP, Waites GMH. 1975. The blood testis barrier. In Creep RO, Astwood EB, Geiger SR, eds. Handbook of physiology Endocrinology V. Washington, DC American Physiological Society. 

The importance of P-glycoprotein expression in the blood-testis barrier, peripheral leukocytes and the kidneys for drug disposition and disease risk is discussed in Sections 8.7.2 and 8.7.3. 

The existence of a barrier between the blood and testes is indicated by the absence of staining in testicular tissue after the intravascular injection of dyes. Morphological studies indicate that the barrier lies beyond the capillary endothelial cells and is most likely to be found at the specialized Sertoli-Sertoli cell junction. It appears that Pgp, the efflux transporter protein, also plays a role in forming this blood-testis barrier. This protein probably plays a role in preventing certain chemotherapeutic agents from reaching specific areas of the testis and thus hinders treatment of the neoplasm. 

Setchell, B.P., and G.M.H. Waites. The blood-testis barrier, pp. 143-172. In R.O. Greep and E.B. Astwood, Eds. Handbook of Physiology. Section 7 Endocrinology. Vol. V Male Reproductive System. Washington, D.C. American Physiological Society, 1975. 

In the tissue cross-reactivity studies, the antibody has equal access to all tissues and all cell components (membrane, cytosol, nucleus) of the tissues on the section. This is not true in vivo where access to the tissues is governed by passive diffusion of the antibody to the tissue. Moreover, unless uptake by tissues is receptor-mediated, cell membranes preclude entrance of an antibody into the cells. In addition there are blood-brain, blood-nerve, blood-eye, and blood-testis barriers characterized by specialized endothelium that reduce movement of immunoglobulin into these protected spaces. Thus, some tissues have relatively little access by antibodies compared to others. Likewise, antigens within cells have little chance of access to the antibody compared to cell membrane or transmembrane antigens. 

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