Aspects of the regulation of human sperm motility

Abstract: In this thesis I address some of the possible causes for oligozoospermia and low sperm motility, two factors that, singly or in combination, are often seen in cases of male subfertility. In the first study we evaluated the effect on human spermatozoa of the toxicity of compounds present in diesel exhaust. The compounds tested were derivatives of 2-nitrofluorene, and some of them were found to drastically lower the motility of human spermatozoa. We concluded that human spermatozoa may be a working model system for testing potentially toxic compounds. Sperm Activating Protein is a complex of immunoglobulin G4 and apolipoprotein A-I, previously shown to be a major extracellular factor that increases sperm motility. In the second study we determined the exact identity of the components. In addition we were able, using selective proteolytic digestion and Western blot, to demonstrate that the apolipoprotein A-I is bound in the Fab-portion of the immunoglobulin G4. Oligozoospermia is an other common abnormality seen in male subfertile patients, and can be due to defects in cell division. In the third study we focused on the synaptonemal complex, which is a structure that takes part in the joining of homologous chromosomes during meiosis. The structure is almost universally conserved in eucaryotic species, and controls the number and distribution of cross-overs and converts these into chiasmata. In this work we found that the synaptonemal complex protein 1 is present in all testicular biopsies from patients with a partial or fully functional spermatogenesis.