Spermatogenesis

Spermatogenesis is the entire process by which spermatogonia, the germ cell population resident in the testis, are transformed into mature spermatozoa. It proceeds continuously throughout postpubertal male life within the seminiferous tubules. The female process is very different: it is initiated prenatally and resumed cyclically.

Within the seminiferous tubules, germ cells at progressively more advanced stages of maturation lie at progressively greater distances from the basement membrane. They move inward toward the lumen as maturation proceeds.

Germ cells develop in close physical association with Sertoli cells. These somatic supporting cells extend from the basement membrane to the tubule lumen and provide structural and nutritional support to the developing germ cells at every stage.

Sertoli cells form tight junctions with one another that create the blood-testis barrier. This immunological barrier shields the developing haploid germ cells from immune attack. These cells express surface antigens the immune system would otherwise recognise as foreign.

Spermatogonia are the diploid germ cell population resident at the basement membrane of the seminiferous tubule. They derive from the primordial germ cells that colonised the testis during embryonic development. They are the stem cell population that continuously sustains spermatogenesis throughout adult male life.

Spermatogonia divide by mitosis, and each division serves two purposes at once:

• A proportion of the daughter cells remain as spermatogonia, replenishing the stem cell population for future cycles
• Another proportion differentiate further and commit to entering meiosis, becoming primary spermatocytes

This dual outcome from a single mitotic division allows spermatogenesis to continue essentially indefinitely from puberty into old age. In contrast, the oocyte pool is fixed and non-renewing, established in the female before birth.

A spermatogonium committed to differentiation undergoes a final mitotic division and then enters meiosis I as a primary spermatocyte. This is the largest germ cell recognisable within the seminiferous tubule.

It is the diploid cell population in which the full complexity of meiotic prophase I occurs: synapsis, crossing over, and chiasma formation.

Primary spermatocytes remain in prophase I for an unusually prolonged period relative to the rest of the meiotic sequence. This reflects the extensive molecular processes that must occur correctly, synaptonemal complex formation and completion of recombination, before the cell can safely proceed to the first meiotic division.

Completion of meiosis I produces two secondary spermatocytes from each primary spermatocyte, each now haploid in chromosome number, 23 chromosomes, though each chromosome still comprises two sister chromatids.

Secondary spermatocytes are notably short-lived, proceeding rapidly into and through meiosis II without any equivalent prolonged arrest, since the essential, time-consuming recombination events of meiosis have already been completed during meiosis I; secondary spermatocytes are consequently difficult to identify on routine histological sections of the testis simply because they exist, at any given moment, only very transiently.

Completion of meiosis II produces spermatids from each secondary spermatocyte. Spermatids are haploid cells containing a single copy of the genome, 23 single chromatids. A single primary spermatocyte therefore gives rise to four spermatids in total.

At this stage spermatids are round, non-motile cells. Structurally they still resemble a fairly typical, rounded cell, not the highly specialised, streamlined mature spermatozoon.

They must undergo an extensive further structural transformation, spermiogenesis, to acquire the structure and motility required for their reproductive function.

Mature spermatozoa are the final, fully differentiated product of spermatogenesis. They are released into the lumen of the seminiferous tubule in a process termed spermiation.

They are then transported through the remainder of the male reproductive tract, where they undergo further functional maturation, including acquisition of full motility within the epididymis. Only then can they fertilise an oocyte.

The full sequence proceeds in a fixed order:

• Spermatogonium, undergoing mitosis
• Primary spermatocyte, undergoing meiosis I
• Secondary spermatocyte, undergoing meiosis II
• Spermatid, undergoing spermiogenesis
• Mature spermatozoon

A single spermatogonium committed to this pathway takes approximately 64 to 74 days to complete the entire sequence through to a released, though not yet fully functionally mature, spermatozoon.

The cycle proceeds continuously and asynchronously across different regions of the seminiferous tubules. Mature spermatozoa are therefore produced essentially continuously, in large numbers, throughout adult male reproductive life. This differs from the discrete, cyclical, single-gamete-per-cycle pattern of oogenesis.