Spermatogenesis

SPERMATOGENESIS
Maturation of Sperm Begins at Puberty
Spermatogenesis, which begins at puberty, includes all of the events by which
spermatogonia are transformed into spermatozoa. At birth, germ cells in the
male can be recognized in the sex cords of the testis as large, pale cells surrounded
by supporting cells (Fig. 1.21A). Supporting cells, which are derived
from the surface epithelium of the gland in the same manner as follicular cells,
become sustentacular cells, or Sertoli cells (Fig. 1.21C ).
Shortly before puberty, the sex cords acquire a lumen and become the
seminiferous tubules. At about the same time, primordial germ cells give
rise to spermatogonial stem cells. At regular intervals, cells emerge from this
stem cell population to form type A spermatogonia, and their production
marks the initiation of spermatogenesis. Type A cells undergo a limited number
of mitotic divisions to form a clone of cells. The last cell division produces
type B spermatogonia, which then divide to form primary spermatocytes
(Figs. 1.21 and 1.22). Primary spermatocytes then enter a prolongedprophase (22 days) followed by rapid completion of meiosis I and formation
of secondary spermatocytes. During the second meiotic division, these cells
immediately begin to form haploid spermatids (Figs. 1.21–1.23). Throughout
this series of events, from the time type A cells leave the stem cell population
to formation of spermatids, cytokinesis is incomplete, so that successive
cell generations are joined by cytoplasmic bridges. Thus, the progeny of a single
type A spermatogonium form a clone of germ cells that maintain contact
throughout differentiation (Fig. 1.22). Furthermore, spermatogonia and spermatids
remain embedded in deep recesses of Sertoli cells throughout their
development (Fig. 1.24). In this manner, Sertoli cells support and protect the
germ cells, participate in their nutrition, and assist in the release of mature
spermatozoa.
Spermatogenesis is regulated by luteinizing hormone (LH) production by
the pituitary. LH binds to receptors on Leydig cells and stimulates testosterone
production, which in turn binds to Sertoli cells to promote spermatogenesis.
Follicle stimulating hormone (FSH) is also essential because its binding to
Sertoli cells stimulates testicular fluid production and synthesis of intracellular
androgen receptor proteins.
Spermiogenesis
The series of changes resulting in the transformation of spermatids into spermatozoa
is spermiogenesis. These changes include (a) formation of the acrosome,
which covers half of the nuclear surface and contains enzymes to assist in penetration
of the egg and its surrounding layers during fertilization (Fig. 1.25);
(b) condensation of the nucleus; (c) formation of neck, middle piece, and tail;
and (d) shedding of most of the cytoplasm. In humans, the time required for
a spermatogonium to develop into a mature spermatozoon is approximately
64 days.
When fully formed, spermatozoa enter the lumen of seminiferous tubules.
From there, they are pushed toward the epididymis by contractile elements
in the wall of the seminiferous tubules. Although initially only slightly motile,
spermatozoa obtain full motility in the epididymis.

Abnormal Gametes
In humans and in most mammals, one ovarian follicle occasionally contains
two or three clearly distinguishable primary oocytes (Fig. 1.26A). Although
these oocytes may give rise to twins or triplets, they usually degenerate before
reaching maturity. In rare cases, one primary oocyte contains two or even
three nuclei (Fig. 1.26B). Such binucleated or trinucleated oocytes die before
reaching maturity.
In contrast to atypical oocytes, abnormal spermatozoa are seen frequently,
and up to 10% of all spermatozoa have observable defects. The
head or the tail may be abnormal; spermatozoa may be giants or dwarfs;
and sometimes they are joined (Fig. 1.26C ). Sperm with morphologic abnormalities
lack normal motility and probably do not fertilize oocytes.

Primordial germ cells appear in the wall of the yolk sac in the fourth
week and migrate to the indifferent gonad (Fig. 1.1), where they arrive
at the end of the fifth week. In preparation for fertilization, both
male and female germ cells undergo gametogenesis, which includes meiosis
and cytodifferentiation. During meiosis I, homologous chromosomes
pair and exchange genetic material; during meiosis II, cells fail to replicate
DNA, and each cell is thus provided with a haploid number of chromosomes
and half the amount of DNA of a normal somatic cell (Fig. 1.3). Hence, mature
male and female gametes have, respectively, 22 plus X or 22 plus Y
chromosomes.
Birth defects may arise through abnormalities in chromosome number
or structure and from single gene mutations. Approximately 7% of major
Chapter 1: Gametogenesis: Conversion of Germ Cells Into Male and Female Gametes 29
birth defects are a result of chromosome abnormalities, and 8%, are a result
of gene mutations. Trisomies (an extra chromosome) and monosomies
(loss of a chromosome) arise during mitosis or meiosis. During meiosis, homologous
chromosomes normally pair and then separate. However, if separation
fails (nondisjunction), one cell receives too many chromosomes and
one receives too few (Fig. 1.5). The incidence of abnormalities of chromosome
number increases with age of the mother, particularly with mothers
aged 35 years and older. Structural abnormalities of chromosomes include
large deletions (cri-du-chat syndrome) and microdeletions. Microdeletions
involve contiguous genes that may result in defects such as Angelman syndrome
(maternal deletion, chromosome 15q11–15q13) or Prader-Willi syndrome
(paternal deletion, 15q11–15q13). Because these syndromes depend
on whether the affected genetic material is inherited from the mother or the
father, they also are an example of imprinting. Gene mutations may be dominant
(only one gene of an allelic pair has to be affected to produce an alteration)
or recessive (both allelic gene pairs must be mutated). Mutations responsible
for many birth defects affect genes involved in normal embryological
development.
In the female, maturation fromprimitive germ cell to mature gamete, which
is called oogenesis, begins before birth; in the male, it is called spermatogenesis,
and it begins at puberty. In the female, primordial germ cells form
oogonia. After repeated mitotic divisions, some of these arrest in prophase of
meiosis I to form primary oocytes. By the seventh month, nearly all oogonia
have become atretic, and only primary oocytes remain surrounded by
a layer of follicular cells derived from the surface epithelium of the ovary
(Fig. 1.17). Together, they form the primordial follicle. At puberty, a pool of
growing follicles is recruited and maintained from the finite supply of primordial
follicles. Thus, everyday 15 to 20 follicles begin to grow, and as they mature,
they pass through three stages: 1) primary or preantral; 2) secondary
or antral (vesicular, Graafian); and 3) preovulatory. The primary oocyte remains
in prophase of the first meiotic division until the secondary follicle is
mature. At this point, a surge in luteinizing hormone (LH) stimulates preovulatory
growth: meiosis I is completed and a secondary oocyte and polar
body are formed. Then, the secondary oocyte is arrested in metaphase of
meiosis II approximately 3 hours before ovulation and will not complete this
cell division until fertilization. In the male, primordial cells remain dormant
until puberty, and only then do they differentiate into spermatogonia. These
stem cells give rise to primary spermatocytes, which through two successive
meiotic divisions produce four spermatids (Fig. 1.4). Spermatids go through
a series of changes (spermiogenesis) (Fig. 1.25) including (a) formation of
the acrosome, (b) condensation of the nucleus, (c) formation of neck, middle
piece, and tail, and (d) shedding of most of the cytoplasm. The time required
for a spermatogonium to become a mature spermatozoon is approximately
64 days.