Page 317 - Veterinary Toxicology, Basic and Clinical Principles, 3rd Edition

284 SECTION | II Organ Toxicity

VetBooks.ir number of spermatozoa produced daily by the testes, Differentiation (spermiogenesis)
when determining the period of toxicant exposure relative
Spermatozoa have been aptly characterized as “sophisti-
to the appearance of abnormal spermatozoa in an ejacu-
late and when assessing the severity and reversibility of cated, self-propelled packages of DNA and enzymes”
(Senger, 2003; Evans and Ganjam, 2017). “Differentiation”
toxicant-induced damage to sperm precursors within the or “spermiogenesis” involves all the changes occurring
testes. within the adluminal compartment, which transform round
Spermatogenesis can be subdivided into three phases spermatids into spermatozoa possessing an acrosome for
or stages referred to as “proliferation,” “meiosis” and penetration of the zona pellucida and a tail or flagellum to
“differentiation.” During each of these phases, sperm facilitate motility (Genuth, 2004b). Differentiation can be
precursors or male germ cells (spermatogonia, sperma- subdivided into the “Golgi,” “cap,” “acrosomal” and “mat-
tocytes or spermatids) undergo specific, stepwise uration” phases, which correspond respectively to acroso-
changes as they develop into spermatozoa which will mal vesicle formation; spreading of the acrosomal vesicle
eventually be released into the excurrent duct system. over the nucleus; elongation of the nucleus and cytoplasm
Each of these phases involves a different type of germ and final assembly involving the formation of the post
cell undergoing a different developmental process, and, nuclear cap organization of the tail components (Senger,
as such, these phases have the potential to differ in their 2003; Evans and Ganjam, 2017). Following the nuclear and
susceptibility to the mechanisms of action of various cytoplasmic reorganization which characterizes the changes
reproductive toxicants. to germ cells during spermiogenesis, differentiated sperma-
tozoa are released from Sertoli cells into the lumen
Proliferation (Mitosis or Spermatocytogenesis) of the seminiferous tubules by a process referred to as
The “proliferation” phase of spermatogenesis has also “spermiation.” The complex signaling pathways and geno-
been referred to as “mitosis” or “spermatocytogenesis” mic imprinting involved in regulating the differentiation
and occurs within the basal compartment of the seminifer- of round spermatids into spermatozoa are potential targets
ous tubule. Proliferation denotes all of the mitotic divi- for EDCs.
sions involving spermatogonia (Senger, 2003; Evans and
Ganjam, 2017). A large number of B-spermatogonia The Cycle of the Seminiferous Epithelium
result from the mitoses of several generations of sper-
In most sexually mature mammals, spermatozoa are
matogonia (e.g., A 1 ,A 2 ,A 3 ,A 4 and I; some species varia-
produced continuously, with the entry of germ cells
tions in nomenclature) (Senger, 2003; Genuth, 2004b;
into the proliferation phase of spermatogenesis occurring
Evans and Ganjam, 2017). Stem cell renewal is accom-
in a coordinated cyclic manner (Genuth, 2004b).
plished during proliferation by the reversion of some sper-
Spermatogonia A in a given region of the seminiferous
matogonia to more primitive germ cells (Senger, 2003;
tubule commit to proliferate in a synchronous manner,
Evans and Ganjam, 2017). Germ cell mitosis during
with cohorts of their progeny germ cells (cellular genera-
spermatogenesis ends with the transformation of B-
tions) connected by intercellular bridges and developing
spermatogonia into primary spermatocytes, and this
and differentiating in unison (Thomas and Thomas, 2001;
process is particularly susceptible to toxicants, such as
Senger, 2003, Evans and Ganjam, 2017). Including sper-
chemotherapeutic agents and radiation, which target rap-
matogonia A, four or five generations or concentric layers
idly dividing cells.
of sperm precursors are present in each cross-section of
the seminiferous tubules (Figure 17.1)(Thomas and
Meiosis Thomas, 2001; Senger, 2003; Haschek et al., 2010; Evans
“Meiosis” takes place within the adluminal compartment and Ganjam, 2017). The cycle of the seminiferous epithe-
of the seminiferous tubules and involves the participation lium in most mammals is characterized by germ cells in
of primary and secondary spermatocytes in a total of two each spermatogenic phase associating with contiguous
meiotic divisions. The chromosomal reduplication, syn- generations in a repeatable pattern of specific cellular
apsis and crossover, as well as cellular division and sepa- associations or “stages” (Thomas and Thomas, 2001;
¸
ration, which occur during this phase of spermatogenesis, Franca et al., 2005). There is generally only one stage per
are extremely complex and guarantee genetic diversity seminiferous tubular cross-section in subprimates (Franc¸a
(Senger, 2003; Genuth, 2004b; Evans and Ganjam, et al., 2005), and each stage transitions into the next at
2017). The meiosis phase of spermatogenesis is consid- predictable intervals (Senger, 2003). At any given point
ered by some to be most susceptible to toxic insult along a seminiferous tubule, the entire cycle of the semi-
(Thomas and Thomas, 2001) and ends with the produc- niferous epithelium occurs over a set time interval closely
tion of haploid round spermatids (Senger, 2003; Evans associated with the spermatogonial turnover rate for that
and Ganjam, 2017). particular mammalian species (Thomas and Thomas, 2001;