It has been reported that a number of drugs and chemicals act
preferentially on spermatogenesis (Fox & Fox, 1967; Patanelli,
1975). A specific action of a toxic compound on spermatogenesis
suggests a specific target in the testicular tubules and may point
to a unique. or at least rare property of spermatogenic cells (or
possibly Sertoli cells) as compared with all (other) somatic cell
types. As indicated in this Introduction, spermatogenic cells
possess a number of particular features. In the present thesis it
was studied whether specific biochemical processes in spermatids
are possible targets for antispermatogenic agents.
Remarkable biochemical properties of advanced spermatogenic
cells include the presence of the testis-specific lactate dehydrogenase
isoenzyme LDH-C 4 (see 1.2) and the deviating energy
metabolism (see 1.2 and Appendix paper). Drugs acting on
mitochondria may preferentially kill spermatogenic cells, since
these cells are highly dependent on mitochondrial function. In the
experiments described in Chapter 2 and 3, effects of the antifertility
agent gossypol on LDH-C4 activity and ATP production in spermatids
were studied. From the biochemical analysis of the preferential
action of gossypol on spermatogenic cells, more can be learned
about biochemical processes which are of particular importance in
the spermatogenic cells. It was observed that gossypol may
interfere with spermatogenesis through an effect on ATP production.
In this context, ATP metabolism in spermatids was studied in
more detail as described in Chapter 4.
Another possible target for antispermatogenic agents is
glutathione metabolism in the testicular tubules (see 1.6). In the experiments described in Chapter S, glutathione S-transferase
substrates and oxidizing agents were applied to study the presence
of GSH-dependent defence mechanisms in round spermatids. In
Chapter 6, it is evaluated to what extent the GSH-dependent
defence systems in spermatids can provide protection against
xenobiotics and the induction of DNA damage by ionizing radiation.
The possible role of Sertoli cells in the de novo glutathione
biosynthesis in seminiferous tubules is indicated in Chapter 7. In
the experiments described in this Chapter 7 the glutathione
biosynthesis in isolated testicular cells and tubule fragments was
studied, making use of the glutathione-depleting agent diethyl
maleate and the glutathione biosynthesis inhibitor buthionine
sulfoximine.
It is anticipated that improved understanding of the action of
different compounds on biochemical processes in Sertoli cells and
spermatogenic cells, may provide working hypothesises to test and
identify antispermatogenic agent
