Altered molecular dynamics and antioxidant status in the spermatozoa in testosterone-induced oligospermia in mouse.

Abstract

Though supraphysiological doses testosterone (T) and its derivatives are known to suppress spermatogenesis in mammals by interfering with the hypothalamus-pituitary axis leading to oligozoospermia, no study has been performed to evaluate the integrity of the sperm cells produced by such individuals. In T-induced oligozoospermia in the mouse, the spermatozoa showed suppressed zona-binding ability though the motility and viability remained unchanged. In order to assess whether this decreased zona-binding ability is due to perturbations in the mechanical properties of the sperm membranes, we attempted to examine the molecular dynamics employing a lipophilic spin label (16-doxyl stearate) and a protein-binding label (Mal-Net) in two sets of independent experiments. The results showed that the rotational freedom of lipophilic molecules reduced significantly within the first week of T-treatment. During weeks 1 through 4, the protein rotation was found to be retarded significantly. We observed a sharp increase in the ascorbyl radical associated with the cauda epididymal spermatozoa and epididymal fluid of testosterone-treated mice. Moreover, the glutathione (GSH) content in the spermatozoa and the epididymal fluid increased significantly after testosterone-treatment. Further, there was a elevation in the superoxide dismutase (SOD) activity and suppression in the superoxide anion radical generated by the cauda epididymal spermatozoa of testosterone-treated animals. A change in the mechanical properties of a bilayer could modify both the mechanical properties and the function of incorporated proteins. In many instances, a liquid-crystalline bilayer is necessary for protein function. It is likely that the change in the physical properties of sperm membranes might cause the inhibition of enzymes associated with spermatozoa after T-treatment. The alterations in the sperm membrane structure and the antioxidant potentials of both the spermatozoa and the cauda epididymal fluid could also account for the decrease in the zona-binding index of the spermatozoa in T-treated animals. Thus, this study demonstrates for the first time that supraphysiological doses of testosterone could modify the mechano-dynamic properties of sperm membranes and could perturb the redox status of both spermatozoa and the epididymal fluid.

• Authors: S B Purohit, D Saxena, M Laloraya, P Kumar G
• Journal: Molecular reproduction and development (Mol Reprod Dev) Vol. 55 Issue 3 Pg. 316-25 (Mar 2000) ISSN: 1040-452X [Print] United States
• PMID: 10657051 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2000 Wiley-Liss, Inc.

Chemical References

• Antioxidants
• Free Radicals
• Testosterone
• Superoxide Dismutase
• Glutathione

Topics

• Animals
• Antioxidants (metabolism)
• Cell Membrane (metabolism)
• Female
• Free Radicals (metabolism)
• Glutathione (metabolism)
• Male
• Mice
• Oligospermia (metabolism)
• Oxidation-Reduction
• Sperm Count (drug effects)
• Spermatozoa (drug effects, metabolism)
• Spin Trapping
• Superoxide Dismutase (metabolism)
• Testosterone (pharmacology)
• Time Factors
• Zona Pellucida (metabolism)