Spermatotoxic Effect of Methanol Extract of Quassia amara L.: Impact on Expression of Specific Genes Concerned with Ubiquitination-Proteosome Degradation Pathway

Abstract

Ubiquitination is believed to play a critical role in removal of dead and/or defective spermatozoa in normal and, more importantly, under circumstances when such spermatozoa are produced in large numbers due to genetic defects or toxic manifestations. Ubiquitination under such instances would involve specific gene expressions, many of which are not yet clearly understood. In an exhaustive study in Swiss mouse model to find the spermatotoxic effect of quassin, a diterpene compound isolated from Quassia amara , we found most of the spermatozoa to be abnormal in morphology and unviable. In the present study, we aimed at analysing the transcriptional profile of three selected genes, Ubb, Ube2c and Psmb8, involved in the ubiquitin proteolytic pathway in the testis and epididymal segments of Q. amara bark methanol extract treated mice adopting semi-quantitative RT-PCR and to study the level of DNA damage of the treated mouse spermatozoa. The results revealed that the treatment induced considerable damage to the sperm DNA. All the three genes studied showed marked increase in their levels of expression in the treated mice compared to the corresponding controls. Thus, this study shows that Q. amara methanol extract is causative of sperm DNA damage and defective spermatozoa and, in such cases, the expression of specific genes concerned with ubiquitination pathway is increased, implying that ubiquitination-proteosomal degradation is involved in the processing of dead/defective spermatozoa.