Energy- and glutathione metabolism in spermatids as possible targets for antispermatogenic agents

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

Search for charged Higgs bosons in e+ e- collisions at s**(1/2) = 189-GeV - 202-GeV

A search for pair-produced charged Higgs bosons was performed in the high energy data collected by the DELPHI detector at LEP II at centre-of-mass energies from 189 GeV to 202 GeV. The three different final states, \tau \nu \tau \nu, c \bar s \bar c s and c \bar s \tau \nu were considered. New methods were applied to reject wrong hadronic jet pairings and for the tau identification, where a discriminator based on tau polarisation and polar angles was used. No excess of data compared to the expected Standard Model processes was observed and the existence of a charged Higgs boson with mass lower than 71.5 GeV/c^2 is excluded at the 95% confidence level.Comment: 19 pages, 6 figure