TESTICULAR DEVELOPMENT AND
SPERMATOGENESIS
Histologically, newborn testes appear as
“testis cords” that harbor mainly Sertoli cells and rarer early germ cells,
called gonocytes, in layers without tubular lumina. Consistent with a brief
surge in androgen levels during the first few months of life that is thought to
hormonally imprint later androgen-dependent organs, large prominent
interstitial Leydig cells occupy the spaces among the testis cords. In early
childhood, little change occurs in the testis cords except for linear growth.
At 5 to 7 years of age, lumina begin to appear in the cords and they gradually
increase in diameter to become seminiferous tubules, characterized by primitive
spermatogonial stem cells and marking the first stage of spermatogenesis.
Mitotic activity of early spermatogonia begins at about 11 years of age;
however, the age at which the germ cells begin to differentiate varies greatly,
as does the onset of puberty. Primary spermatocytes appear soon thereafter,
indicating the beginning of meiosis in the testis, and spermatids are noted at
about 12 years of age. Once this germ cell maturation sequence (termed spermarche)
begins, the testes enlarge rapidly and constitute one of the first signs of
puberty (Tanner stage I).
The interstitial Leydig
cells mature concurrently with germ cells during early puberty, but androgen
production lags slightly behind spermatogenesis. The pubertal surge in
testosterone from mature Leydig cells is responsible for the remainder of
pubertal development (Tanner stages II to V). Spermatogenesis remains active
throughout adult life but decreases during the seventh or eighth decade with
the onset of andropause, as a response to decreased androgen production by
Leydig cells.
Spermatogenesis is a
continuous process in vertebrates (only seasonal in some moose species) and, in
males, involves germ cell progression though 13 cell types over a period of 64
days. It consists of (1) a proliferative phase as spermatogonia divide to
replace their number (self-renewal) or differentiate into daughter cells that
become mature gametes; (2) a meiotic phase when germ cells undergo a reduction
division, resulting in haploid (half the normal DNA complement) spermatids; and
(3) a spermiogenesis phase in which spermatids undergo a profound metamorphosis
to become mature sperm.
Spermatogenesis begins with
type B spermatogonia dividing mitotically to form primary spermatocytes within
the adluminal compartment. Primary spermatocytes are the first germ cells to
undergo meiosis. As they move from the adluminal or basal to luminal or apical
compartment of the Sertoli cell (as defined by intercellular tight junctions),
they divide into secondary spermatocytes. The latter cleave immediately into
spermatids, which metamorphose into mature sperm.
A cycle of spermatogenesis
involves the division of spermatogonial stem cells into sperm. Several cycles
of spermatogenesis coexist within the germinal epithelium at any one time and
are described morphologically as stages. When viewed from a fixed point within a
seminiferous tubule, six recognizable stages exist in humans. Superimposed on
this, there is also a specific organization of spermatogenic cycles within the
seminiferous tubule space, termed spermatogenic waves. It is likely that human
spermatogenesis occurs in a spiral or helical wave pattern that
ensures constant and not pulsatile sperm production at 1200 sperms/heartbeat.
There are two important
differences between mitosis and meiosis. During the phase of DNA synthesis in
both mitosis and meiosis, reproducing cells have double the normal content of
DNA (4n). In mitosis, DNA content is reduced to diploid (2n) after a
single reduction division. However in meiosis, a second reduction division
(secondary spermatocytes to spermatids) occurs to generate
daughter cells with haploid (n) DNA content consisting of 22 autosomes
and either an X or a Y chromosome. The other difference is that mitosis
produces identical daughter cells, whereas genetically different daughter cells
result from meiosis. This occurs as a consequence of chromosomal synapse and recombination
during meiosis, in which DNA is exchanged between sister chromatids and is the
basis for genetic diversity in our species.
