Spermatogenesis represents the process by which precursors termed spermatogonia undergo a complex series of divisions to give rise to spermatozoa (4,5). This process takes place within the seminiferous epithelium which is a complex structure composed of germ cells and radially oriented supporting cells called Sertoli cells (Figure 5). The latter cells extend from the basementmembrane of the seminiferous tubules to reach the lumen. The cytoplasmic profiles of the Sertoli cells are extremely complex as this cell extends a series of processes that surround the adjacent germ cells in an arboreal pattern (5-7).
Spermatogenesis can be divided into three major phases (i) proliferation and differentiation of spermatogonia, (ii) meiosis, (iii) spermiogenesis which representsa complex metamorphosis involved in the transformation of round spermatids arising from the final division of meiosis into the complex structure of the spermatozoon.
Spermatogonial Renewal and Differentiation
These cells represent a population that divide by mitosis providing both a renewing stem cell population as well as spermatogonia that are committed to enter the meiotic process. Theidentification of different types of spermatogonia is complex due to a lack of definitive markers that can identify specific stages. To date, classification of these cells has depended on the features of their nuclei and, in particular, their chromatin patterns (5). The identification of the latter, which represents a crucial step in classification, is often obscured by poor fixation especially if thetissue is fixed in formalin. The ideal fixatives for testicular tissue are Bouin's or Cleland's solution. In general two main classes of spermatogonia can be identified in all mammals: Type A exhibiting fine pale staining nuclear chromatin and Type B with coarse chromatin collections found close to the nuclear membrane(8). In many mammals, the Type A spermatogonia can be divided into severalsubtypes that may represent different phases of proliferation and progression towards Type B spermatogonia. The Type B spermatogonia are generally agreed to represent the cells which differentiate and enter into the process of meiosis where they are called primary spermatocytes(9).
In the human and other primates, the Type A spermatogonia can be further divided into A dark (Ad) and A pale (Ap)(9)Some investigators have proposed that the Ad spermatogonia represent the reserve or non-proliferative spermatogonial population which can give rise to Ap(10-12) whereas others have suggested that the Ap spermatogonia are the true stem cell of the testis(13). Some of these differences arise from the difficulties in identifying spermatogonial cell types.
Spermatogonia do not separate completelyafter meiosis due to incomplete cytokinesis and remain joined by intercellular bridges (14). These intercellular bridges persist throughout all stages of spermatogenesis and are thought to facilitate biochemical interactions allowing synchrony of germ cell maturation.
Following damage to the seminiferous epithelium, some investigators have suggested new criteria which may facilitate theidentification of the true spermatogonial stem cell within the epithelium. These criteria have emerged from studies of investigators engaged in transplantation of germ cells into the testis. Following the induction of cryptorchidism, the surviving spermatogonia, from which restoration of spermatogenesis is possible, show the presence of α6β1 integrin (15). The studies of Brinster and colleagues have shownthat transplantation of spermatogonial populations can restore spermatogenesis in infertile recipients (15a-d). Further our understanding of some of the factors controlling spermatogonial stem cell proliferation have emerged and involve such proteins as Glial-derived neurotropic factor (15e-i).
This process commences when Type B spermatogonia lose their contact with the basement...