Physiology, sperm maturation

"If anyone asks what the epididymis is, we shall answer that it is a vessel constituting by various twists a body affixed to the back of the testicle'' (deGraaf, 1668; see Jocelyn and Setchell, 1972).

Spermatozoa leave the testis neither fully motile nor able to recognize or fertilize an egg, but must traverse a long duct, the epididymis, to acquire these abilities. These transformations of spermatozoa are called sperm maturation. For a number of years, the epididymis was considered a holding tube for the spermatozoa; the epididymis did not influence the process of sperm maturation, but was a place where spermatozoa aged. It was felt that sperm maturation was inherent to the spermatozoa and had little to do with the epididymis. Because it takes anywhere from 1 to 14 days for spermatozoa to traverse the epididymis, the aging hypothesis seemed reasonable. However, it is now very clear that the epididymis is actively involved in the sperm maturation process, not only providing an appropriate environment but also providing many of the molecules needed by the spermatozoa to allow them to fertilize an egg.

Structure of the epididymis
Looking at the gross structure of the epididymis of several species, the organ can be divided into a number of segments or regions: initial segment, caput (head), corpus (body), cauda (tail) and the vas deferens ( Fig. 1). There has been much discussion of the precise delineation of each epididymal region as it related to the gross structure of the organ, to the physiological process within the organ and to the localization of discrete stages of sperm maturation. For example, sperm motility is generally observed as the spermatozoa pass through the caput region whereas sperm fertilizing ability is usually achieved as the spermatozoa pass through the corpus. Spermatozoa are eventually stored within the cauda region. The gross structure of the human epididymis is unique among the species studied in that it does not have a prominent cauda region. Hence the human epididymis has little capacity to store large numbers of spermatozoa as compared with many other species, for example the ram or bull.

Histologically the epididymis is composed of several cell types including principal, basal, apical, halo, clear, and narrow cells, each of which vary in number and size along the epididymal duct. The principal cells in the more proximal regions of the epididymis tend to be very tall resulting in a duct with a small luminal diameter whereas, in the distal regions, the principal cells are low columnar cells and the luminal diameter much larger (Fig. 1). Such dramatic differences in the cellular architecture are primarily due to the functional roles of each cell within each epididymal region. In the proximal region there is considerable absorption of water, hence the cells take on the classical appearance of a water absorbing epithelium -large apical surface area with long stereocilia, and many mitochondria in the basal aspects. The distal epididymis is primarily a sperm storage region, hence the cells are much smaller and some cells, for example the clear cells, are specialized for removing cellular debris.

Ultrastructurally, epididymal cells in general can be seen to have an extensive endoplasmic reticulum and an elaborate Golgi apparatus, reflecting the involvement of this tissue in protein synthesis. Tight junctional complexes between the epididymal cells form what is referred to as the blood-epididymis barrier, an important physiological and anatomical barrier that allows the epididymis to create a specialized fluid environment for the maturing spermatozoa. It has also been suggested that another function of the blood-epididymis barrier is immunological protection of the spermatozoa. Spermatozoa are immunogenic and must be protected from the immune system during their transit along the epididymal duct.

Maturation of spermatozoa
It is the fluid microenvironment within the epididymis that has been suggested to promote maturation of the spermatozoa. The fluid is hyperosmotic and distinctly different in composition from blood plasma. In the epididymis of many species the major constituents are organic solutes: L-carnitine, myo-inositol, glutamate, taurine, glycerophosphorylcholine, sialic acids, lactate, and certain steroids such as dihydrotestosterone. Concentrations of these organic solutes can reach anywhere from 20 to 90 mM depending upon the species and the epididymal region. The luminal fluid also contains several ions: sodium, potassium, chloride and bicarbonate. The fluid in the proximal epididymis is quite acidic with pH values in the 6.5 range increasing to approximately 6.8 in the distal epididymis. The role of each organic solute and ion is not precisely known but several studies suggest they are involved in the acquisition of motility, in osmoregulation for spermatozoa and epididymal epithelial cells, and in sperm and epididymal cell metabolism. There are also several proteins found within the lumen including transferrin, albumin, clusterin (SGP-2), immobilin, retinoid-binding proteins, metalloproteins, proenkephalin, and enzymes such as glycosyltransferases, glycosidases, glutathione peroxidase, and gamma- glutamyl transpeptidase. Several of these proteins have been shown to be associated with spermatozoa suggesting a role in sperm maturation and/or sperm-egg interactions. However, the role of most of these proteins is not yet clear.

Other functions of the epididymis
In addition to promoting sperm maturation and providing a place for sperm storage, the epididymis plays a role in the transport of spermatozoa along the duct and protects spermatozoa from harmful substances. Spermatozoa within the epididymis of several species are held in a quiescent state by luminal fluid factors and, therefore, do not propel themselves along the duct. Transport of spermatozoa is achieved by two processes, contractions of the smooth muscle that surrounds the epididymal epithelium, and the continuous production and movement of fluid originating from the testis. Protection of spermatozoa from harmful substances such as xenobiotics and oxygen radicals is an important aspect of epididymal function. The manner by which this is achieved is unclear, but it appears that the epididymis has evolved elaborate protective mechanisms. For example, the blood-epididymis barrier regulates the entry of solutes and ions into the lumen, and the luminal fluid contains antioxidants, e.g., glutathione, and enzymes such as gamma-glutamyl transpeptidase, superoxide dismutase and glutathione- S-transferase involved in antioxidant defense and protection against xenobiotics.

In summary, the epididymis promotes sperm maturation, facilitates the transport of spermatozoa along the duct, stores sperm and protects spermatozoa from harmful substances. All these functions are coordinated with remarkable precision to ensure production of fully viable spermatozoa.

Suggested Reading

Jocelyn HD, Setchell BP. Regnier de Graaf on the human reproductive organs. J Reprod Fert 1972; Suppl. 17:1-222.

Setchell BP, Brooks DE. Anatomy, vasculature, innervation, and fluids of the male reproductive tract. In: Knobil E, Neill JD, eds. The Physiology of Reproduction. New York: Raven Press Ltd.; 1988:753-836.

Robaire B, Hermo L. Efferent ducts, epididymis, and vas deferens: structure, functions, and their regulation. In: Knobil E , Neill JD, eds. The Physiology of Reproduction. New York: Raven Press Ltd.; 1988:999-1080.