160
spermatogenesis can be considered as a particular cellular achievement. Thus, the
testis is considered one of the most complex tissues in the body. This sophisticated
communication network has a weak point, such that the dysfunction of one cell type
spreads to all other cell types in cascade. This largely explains the particular vulnerability of the testis to exogenous molecules from the environment, and more specifically drugs and xenobiotics. It also explains the general difficulty encountered by
the toxicologist in identifying the testicular cell target of a given toxicant and hence
its precise mode of action. More or less complex culture systems of isolated testicular cells have been developed over the past decades which represent very useful
tools for the toxicologist. Among the different testicular cell types, Sertoli and
Leydig cells, have been the ones most usually used for the in vitro analysis of toxic
compounds. While Sertoli cells are used in vitro for mechanistic toxicology studies,
the extreme fragility of germ cells prevents their culture for that purpose. However,
Sertoli and germ cells can be cultured together for short periods of time.
10.3 The Epididymal Function
The mammalian epididymis is major organ of the male excurrent duct system. It is a
single, narrow, tightly-coiled tubule connecting the testis (i.e., efferent ducts) to the
vas deferens. Its unraveled length was estimated as 6-7 meters in humans with a gross
anatomical structure consisting of three histologically and functionally distinct
regions, i.e., the caput, corpus and cauda. (for a review see refrence [22]. The epididymis fulfills major functions that are: (i) the storage of spermatozoa produced by the
testis; (ii) the preservation of viability for these stored gametes; and (iii) the post-testicular maturation of sperm (for a review see reference [23]. Interestingly, the caput
epididymis that is characterized histologically by a thick epithelium with long stereocilia, is involved in absorbing fluid to make the sperm more concentrated.
The epididymis is covered by a two layered pseudostratified epithelium separated from the connective tissue wall by a basement membrane. The two major cell
types form the majority of the epithelium. The so-called Principal cells are columnar shaped and equipped in the caput with stereocilia, long cytoplasmic projections
with an actin filament backbone that project into the lumen. Principal cells actively
secrete numerous molecules into the lumen. Shorter and pyramid-shaped Basal
cells which contact the basal lamina are thought to be undifferentiated precursors of
principal cells. Stereocilia in the epididymis are non-motile. These membrane
extensions aim at increasing the surface area of the cell, allowing for greater absorption and secretion capabilities.
Although morphologically complete, spermatozoa released from the testis are
immotile and do not fulfill the requirements for a correct fertilization process (for a
review see [23]. Thus, large volumes of testicular fluid are secreted by Sertoli cells
to propel them to the epididymis. The core function of stereocilia is to resorb most
of this fluid and to create a fluid current that will move immotile sperm deeper into
the epididymis.
C. Pineau
spermatogenesis can be considered as a particular cellular achievement. Thus, the
testis is considered one of the most complex tissues in the body. This sophisticated
communication network has a weak point, such that the dysfunction of one cell type
spreads to all other cell types in cascade. This largely explains the particular vulnerability of the testis to exogenous molecules from the environment, and more specifically drugs and xenobiotics. It also explains the general difficulty encountered by
the toxicologist in identifying the testicular cell target of a given toxicant and hence
its precise mode of action. More or less complex culture systems of isolated testicular cells have been developed over the past decades which represent very useful
tools for the toxicologist. Among the different testicular cell types, Sertoli and
Leydig cells, have been the ones most usually used for the in vitro analysis of toxic
compounds. While Sertoli cells are used in vitro for mechanistic toxicology studies,
the extreme fragility of germ cells prevents their culture for that purpose. However,
Sertoli and germ cells can be cultured together for short periods of time.
10.3 The Epididymal Function
The mammalian epididymis is major organ of the male excurrent duct system. It is a
single, narrow, tightly-coiled tubule connecting the testis (i.e., efferent ducts) to the
vas deferens. Its unraveled length was estimated as 6-7 meters in humans with a gross
anatomical structure consisting of three histologically and functionally distinct
regions, i.e., the caput, corpus and cauda. (for a review see refrence [22]. The epididymis fulfills major functions that are: (i) the storage of spermatozoa produced by the
testis; (ii) the preservation of viability for these stored gametes; and (iii) the post-testicular maturation of sperm (for a review see reference [23]. Interestingly, the caput
epididymis that is characterized histologically by a thick epithelium with long stereocilia, is involved in absorbing fluid to make the sperm more concentrated.
The epididymis is covered by a two layered pseudostratified epithelium separated from the connective tissue wall by a basement membrane. The two major cell
types form the majority of the epithelium. The so-called Principal cells are columnar shaped and equipped in the caput with stereocilia, long cytoplasmic projections
with an actin filament backbone that project into the lumen. Principal cells actively
secrete numerous molecules into the lumen. Shorter and pyramid-shaped Basal
cells which contact the basal lamina are thought to be undifferentiated precursors of
principal cells. Stereocilia in the epididymis are non-motile. These membrane
extensions aim at increasing the surface area of the cell, allowing for greater absorption and secretion capabilities.
Although morphologically complete, spermatozoa released from the testis are
immotile and do not fulfill the requirements for a correct fertilization process (for a
review see [23]. Thus, large volumes of testicular fluid are secreted by Sertoli cells
to propel them to the epididymis. The core function of stereocilia is to resorb most
of this fluid and to create a fluid current that will move immotile sperm deeper into
the epididymis.
C. Pineau