Figure 2117

Electron micrograph of Sertoli cell junctions. This electron micrograph demonstrates a Sertoli-to-Sertoli junctional complex and, in close proximity, a Sertoli-to-spermatid junctional specialization. Condensation and shaping of the spermatid nucleus (N) are well advanced. The acrosome (A) of the spermatid appears as a V-shaped profile, and in close association with it is the Sertoli cell junctional specialization characterized by bundles of microfilaments that are cut in cross section (arrows). The associated profile of endoplasmic reticulum resides immediately adjacent to the microfilament bundles. The Sertoli-to-Sertoli junction lies below, joining one Sertoli cell (S]) to the adjacent Sertoli cell (S2). The arrowheads indicate the limits of the junction. Note that the junction here reveals the same elements, the microfilament bundles (arrows) and a profile of endoplasmic reticulum, as are seen in the Sertoli-to-spermatid junctional specialization. Not evident at this magnification is the tight junction associated with the Sertoli-to-Sertoli junctional complex. x30,000.

microtubules basal lamina

Sertoli-to-Sertoli junctional specialization spermatogonium late spermatid early spermatid

Golgi apparatus sER

Sertoli-to-spermatid junctional specialization primary spermatocyte karyosome fil

Two basic facts are well established about the immunologic importance of the blood-testis barrier:

• Spermatozoa and spermatogenic cells possess molecules that are unique to these cells and are recognized as "foreign" (not self) by the immune system.

• Spermatozoa are first produced at puberty, long after the individual has become immunocompetent, i.e., capable of recognizing foreign molecules and producing antibodies against them.

Failure of the spermatogenic cells and spermatozoa to remain isolated results in the production of sperm-specific antibodies. Such an immune response is sometimes seen after vasectomy and in some cases of infertility. After vasectomy, sperm-specific antibodies are produced as the cells of the immune system are exposed to the spermatozoa that may leak from the severed ductus deferens. Thus, sperm no longer remain isolated from the immune system within the reproductive tract. In some cases of infertility, sperm-specific antibodies have been found in the semen. These antibodies cause the sperm to agglutinate, preventing movement and interaction with the ovum.

tional specializations of the Sertoli cells include gap junctions between Sertoli cells, desmosome-like junctions between Sertoli cells and early-stage spermatogenic cells, and hemidesmosomes at the Sertoli cell-basal lamina interface.

The Sertoli cell-to-Sertoli cell junctional complex divides the seminiferous epithelium into basal and luminal compartments

The Sertoli cell-to-Sertoli cell junctions establish two epithelial compartments, a basal epithelial compartment and a luminal compartment. Spermatogonia and early primary spermatocytes are restricted to the basal compartment, i.e., between the Sertoli cell-to-Sertoli cell junctions and the basal lamina. More mature spermatocytes and spermatids are restricted to the luminal side of the Sertoli cell-to-Sertoli cell junctions. Early spermatocytes produced by mitotic division of type B spermatogonia must pass through the junctional complex to move from the basal compartment to the luminal compartment. This movement occurs via the formation of a new junctional complex between Sertoli cell processes that extend beneath the newly formed spermatocytes, followed by the breakdown of the junction above them. Thus, in the differentiation of the spermatogenic cells, the processes of meiosis and spermiogenesis occur in the luminal compartment.

In both compartments, spermatogenic cells are surrounded by complex processes of the Sertoli cells. Because of the unusually close relationships between Sertoli cells and differentiating spermatogenic cells, it has been suggested that Sertoli cells serve as "nurse," or supporting, cells, i.e., they function in the exchange of metabolic substrates and wastes between the developing spermatogenic cells and the circulatory system.

In addition, Sertoli cells phagocytose and break down the residual bodies formed in the last stage of spermiogenesis. They also phagocytose any spermatogenic cells that fail to differentiate completely.

The Sertoli cell-to-Sertoli cell junctional complex is the site of the blood-testis barrier

In addition to the physical compartmentalization described above, the Sertoli cell-to-Sertoli cell junctional complex also creates a permeability barrier called the blood-testis bairier. This barrier is essential in creating a physiologic compartmentalization within the seminiferous epithelium with respect to ionic, amino acid, carbohydrate, and protein composition. Therefore, the composition of the fluid in the seminiferous tubules and excurrent ducts differs considerably from the composition of the blood plasma and testicular lymph.

Plasma proteins and circulating antibodies are excluded from the lumen of the seminiferous tubules. The exocrine secretory products of the Sertoli cells, particularly 90-kDa androgen-binding protein (ABP), which has a high binding affinity for testosterone and DHT, are highly concentrated in the lumen of the seminiferous tubules and maintain a high concentration of testosterone, which provides a favorable microenvironment for the differentiating spermatogenic cells.

Most importantly, the blood-testis barrier isolates the genetically different and therefore antigenic haploid germ cells (secondary spermatocytes, spermatids, and sperm) from the immune system of the adult male. Antigens produced by, or specific to, the sperm are prevented from reaching the systemic circulation. Conversely, -y-globulins and specific sperm antibodies found in some individuals are prevented from reaching the developing spermatogenic cells in the seminiferous tubule.

Therefore, the blood-testis barrier serves an essential role in isolating the spermatogenic cells from the immune system.

Sertoli cells have both exocrine and endocrine secretory functions

In addition to secreting fluid that facilitates passage of the maturing sperm along the seminiferous tubules to the intratesticular ducts, Sertoli cells secrete ABP. ABP concentrates testosterone in the luminal compartment of the sem iniferous tubule, where high concentrations of testosterone are essential for normal maturation of the developing sperm.

Sertoli cells also secrete several endocrine substances such as inhibin, a 32-kDa glycoprotein hormone involved in the feedback loop that inhibits FSH release from the anterior pituitary gland. Sertoli cells, themselves, are stimulated by both FSH and testosterone. In addition, Sertoli cells also synthesize plasminogen activator, which converts plasminogen to the active proteolytic hormone plas-min) and transferrin (an iron-transporting protein). FSH receptors are believed to be present only on Sertoli cells and are essential for the secretion of ABP, inhibin, and plasminogen activator (Fig. 21.18).

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