Germ cell development in the testis (including mitosis, meiosis, spermiogenesis), Sertoli cells, other cell types

Spermatogenesis is an elaborate process of cell differentiation starting with a non-differentiated spermatogonial germinal stem cell and terminating with a fully differentiated highly specialized motile cell called a spermatozoon (Fig. 1). The formation of spermatozoa takes place within narrow coiled seminiferous tubules which form the bulk of the testis. Each seminiferous tubule, approximately half a millimeter in diameter, may be close to one meter in length. These tubules have a central fluid-filled lumen and a wall called the seminiferous epithelium composed of germinal cells and of somatic cells, the Sertoli cells, which support and nourish the germinal cells.

Spermatogenesis may be subdivided into three main phases, each involving a class of germinal cells.

First phase: The spermatogonia are immature germinal cells located at the base of the seminiferous epithelium. In man, there are three types of spermatogonia: the pale type A spermatogonia or Ap, the dark type A spermatogonia or Ad, and the type B spermatogonia. The Ap spermatogonia divide by mitosis and give rise either to new type Ap cells or to the more differentiated type B spermatogonia. Thus, the Ap cells may be thought of as self-renewing stem cells since they can produce both new Ap stem cells and a new class of type B spermatogonia. The Ad spermatogonia, which rarely divide in normal adults, are tentatively considered as dormant reserve stem cells. The type B spermatogonia produced by the Ap cells all divide by mitosis to yield differentiated spermatocytes. Thus, the spermatogonial population not only maintains itself, but continuously yields crops of spermatocytes.

Second Phase: Spermatocytes are ceIls which are unique in undergoing two successive special cell divisions, the so-called reductional or meiotic divisions, that produce, the spermatids. These cells have exactly half the number of chromosomes contained by the nuclei of cells that compose the rest of the body. Spermatids are said to be haploid while somatic cells are diploid. In man, somatic cells contain 46 chromosomes and spermatids and spermatozoa contain 23 chromosomes. The fusion of an haploid spermatozoon with an equally haploid ovum restores the diploid number of chromosomes in the cells of the embryo.

Because there are two meiotic divisions, there are two generations of spermatocytes: primary and secondary. At an early or preleptotene stage, the nuclei of primary spermatocytes replicate their DNA content. Fine filamentous chromosomes subsequently appear in the nucleus and the cells are at the leptotene stage. Soon after, homologous chromosomal filaments approximate each other and form close pairs, a phenomenon called synapsis, and the cell is at the zygotene stage. Then each chromosomal pair shortens and thickens and the chromosomes assume the pachytene configuration. The spermatocytes go through an early, mid and late pachytene stage during which the cell and its nucleus progressively increase in volume. The pachytene nucleus also has a prominent nucleolus indicating that these nuclei are actively synthesizing ribosomal RNA which enters the cytoplasm and contributes to the active protein synthesis observed in these cells. Following the long pachytene stage, the primary spermatocytes rapidly complete their first meiotic division going through metaphase, anaphase and telophase during which the homologous chromosomes separate and migrate to the poles of the cell which then splits to form two daughter cells called secondary spermatocytes. These cells undergo a second maturation division after a short interphase which, this time, is not accompanied by DNA replication. During this division, the chromosomes (of which there is an haploid number) split in half and each half reaches the nucleus of the daughter cells, which are now referred to as the spermatids. Thus spermatocytes, through complex regulatory mechanisms and elaborate cell division processes, are converted to haploid spermatids. This process of meiosis is covered in more detail in the following chapter.

Third phase: The newly formed spermatid, a small spheroidal cell, undergoes a dramatic metamorphosis referred to as spermiogenesis. The nucleus progressively elongates as its chromatin condenses, and gradually takes on the flattened and pointed paddle shape that characterizes the head of human spermatozoa. The Golgi apparatus elaborates a secretory-like granule which gradually grows to produce a cap-like structure, the acrosome, over the nuclear membrane. This structure contains the hydrolytic enzymes necessary for the fertilization of the ovum and partly covers the nucleus of the spermatozoon. The centrioles reach the membrane of the nucleus at the pole opposite to that occupied by the acrosome, bind to it and initiate the formation of the contractile components of the tail, i.e. the microtubules that form the axoneme. The mitochondria migrate toward a segment of the growing tail and form the mitochondrial sheath, which constitutes the respiratory organ of the spermatozoon. The spermatid bulk of cytoplasm is eventually discarded as the residual body, which is phagocytosed and eliminated from the seminiferous epithelium by the Sertoli cell.

Thus, the spermatozoon is a streamlined cell 60 mum long with a head and a tail completely encased in a cell membrane. The head is composed of a small compact nucleus covered by the acrosome. The tail is made up of the contractile axoneme associated with other complex cytoskeletal elements and is partly covered by mitochondria. This cell will continue to develop and mature during its transit through the epididymis.

The complexity of the whole process of spermatogenesis explains its marked sensitivity to toxic substances or hormonal imbalance. In addition, many abnormal and degenerating germinal cells are observed during spermatogenesis in normal men. Spermatogenesis takes approximately 60 days, a duration that does not appear to vary from one individual to the next.

Spermatogenesis is possibly one of the most complex processes of cell differentiation taking place in the tissues of adult individuals. Many of its facets remain to be studied and clarified at the molecular level.

Suggested Reading

Dym M. The male reproductive system. In: Weiss L, ed. Histology. Cell and Tissue Biology, fifth edition. New York, Amsterdam, Oxford: Elsevier Biomedical; 1983:1000-1053.
Desjardins C, Ewing LL, eds. Cell and Molecular Biology of the Testis. New York, Oxford: Oxford University Press, Inc., 1993.