Basic Endocrinology

Spermatogenesis

Spermatogenesis refers to the transformation of germ line stem cells into sperm cells within the seminiferous tubules of the testis. This process can be divided into three stages: proliferation, meiosis, and differentiation.

The seminiferous tubules are extensive structures within the testis and are lined by a stratified epithelium that consists of both germinal and somatic (Sertoli) cell types. Spermatogonia are stem cells of the first phase and are located along the basement membrane of the tubule. These cells proliferate by mitotic division and replenish the epithelium by continuously multiplying. In addition to this self-renewal process, the spermatogonia also produce stem cells that move away from the basement membrane towards the fluid-filled lumen of the seminiferous tubule through Sertoli cell junctions. These junctions make up the blood-testis barrier that separates the male sperm cells from the body.

The division of spermatogonia produces spermatocytes, cells of the second phase. Spermatocytes undergo reduction-division by meiosis, a process whereby a single germ cell increases its DNA content and then undergoes two successive nuclear divisions to produce four individual germ cells with half the number of chromosomes of the parent cell. The second meiotic division produces small, round cells known as spermatids that enter the final phase of spermatogenesis.

The immature, undifferentiated spermatid cells undergo spermiogenesis, an extended phase of cellular rearrangements that elongate and differentiate the spermatids into mature sperm. Spermiogenesis includes the following three major changes: (i) formation of the acrosomic system consisting of the hydrolytic enzymes required for sperm-egg interaction and fertilization; (ii) fusion of membranous organelles to the cell body plasma membrane; and (iii) formation of a long tail and loss of excess cytoplasm.

Spermatogenesis is regulated through endocrine interactions between the pituitary gland and Sertoli cells. This endocrine system is referred to as the brain-pituitary-gonad (BPG) axis and involves a series of signaling mechanisms that coordinate mammalian spermatogenesis. Two hormones, follicle-stimulating hormone (FSH) secreted by the pituitary, and androgens (i.e. testosterone) produced by the Leydig (interstitial) cells in the testis, control the functions of the Sertoli cell functions. FSH causes Sertoli cells to secrete androgen-binding protein, and this protein may facilitate germ cell differentiation by binding to androgens. A feedback-inhibition mechanism exists between luteinizing hormone (LH), another pituitary hormone, and the male sex hormones; LH controls androgen production and circulating androgen, in turn, causes a reduction in the production of LH. Although it is understood that FSH and androgens are required for sperm production, the target genes in Sertoli cells that are required for spermatogenesis to occur have not yet been identified.