In mammals, spermatogenesis begins with diploid stem cells that resemble other somatic cells; it ends with highly specialized motile haploid cells that are remarkably unique in appearance and function. Continuous production of spermatozoa throughout life requires that spermatogonia replenish themselves. Type B spermatogonia undergo mitosis to give rise to diploid primary spermatocytes. The spermatocytes then cross the blood-testis barrier formed by the Sertoli tight junctions to the adluminal compartment. Spermiogenesis refers to the acquisition by the germ cell of several organelles and accessory structures such as the acrosome and the flagellum. Testosterone and follicle-stimulating hormone (FSH) are the two major regulatory hormones of spermatogenesis. FSH binding to its receptor activates adenylate cyclase, and the resultant rise in cAMP triggers binding of cAMP response element modulator (CREM) to ACT (activator of CREM). The complex then acts as a molecular master-switch for a number of genes involved in spermatogenesis.

Apoptosis is a highly regulated form of cell death, involving a cascade-like activation of a series of catabolic processes that progressively disassemble the cell. High levels of endogenous maternal estrogens are associated with increased risks of testicular cancer and cryptorchidism in male offspring. In males, smoking negatively affects sperm production, motility, and morphology. Enzymes involved in the steroid biosynthesis pathway are beginning to be recognized as targets for the action of a number of endocrine-disrupting chemicals (EDCs). The blood-testis barrier (BTB) serves to protect spermatogenesis from many potentially cytotoxic drugs and other chemicals. Drugs and medications may have an adverse impact on fertility through a variety of mechanisms including direct toxicity to the testicular germ cells and supporting cells, alterations of the hypothalamic-pituitary-gonadal (HPG) axis, or effects on sexual performance by impairment of libido, erections, or ejaculation.

The Sertoli cell is implicated centrally in spermatogenesis, organogenesis, male phenotypic development, and the hypothalamic-pituitary-gonadal axis. The cytoskeletal architecture of the Sertoli cell, as in many other cells, consists of actin filaments, intermediate filaments, and microtubules. The interaction of adjoining Sertoli cells with each other and with the basement membrane is crucially important to the function of the Sertoli cell: tight junctions and adherens junctions between Sertoli cells allow for the creation of an immunologically privileged space within the seminiferous tubule. This barrier, created by Sertoli cells and the basement membrane, is known as the blood-testis barrier. This chapter provides a brief discussion spermiogenesis and spermiation. Sertoli cells in adult mammals exist as a terminally differentiated, postmitotic population. Regulation of the Sertoli cell in its function as "nurse cell" for developing spermatogenic cells is obviously multifaceted and complex.