Morphological changes induced by cyclophosphamide on the testis of adult albino rats

ABSTRACT

Cyclophosphamide [CP] remains a necessary treatment for severe neoplastic and non neoplastic disorders. Recently it is also used in the control of organ rejection after transplantation as an Immunosuppressive chemotherapeutic agent. For patients receiving chemotherapy containing CP, the major concern is gonadal dysfunction with, impaired reproductive capacity. To assess how CP exposure produces testicular toxicity, the present study, try to show the morphological and ultrastructural effects induced by CP treatment on the rat testis and the possible reversibility of these effects with rehabilitation. Thirty adult male rats were treated intraperitoneally for five successive weeks with saline or CP dissolved in 5% dextrose [100mg/kg/week]. Semithin and ultrathin sections from testicular tissue were examined one week and 6 weeks [rehabilitation period] after stopping the treatment. Atrophic shrunken seminiferous tubules with markedly distorted shape were revealed in semithin sections of CP treated rats. Many vacitoles and areas of separations between the spermatogenic cells were detected in the tubules which were more numerous towards the basement membrane. The interstitial spaces showed increase in its mount with moderately dilated blood vessels. Different degenerative changes in the nucleus and cytoplasm could be seen in the form of disruption of cell and nuclear membranes, malformed nucleus with condensed chromatin or vacuolization of the cytoplasm, degenerated mitochondria and accumulation of lipid droplets in the germinal cells of CP treated seminiferous tubules by electron microscopy. Type A spermatogonia were predominantly affected that they were rarely seen or replaced by degenerative muoles, Spermatids were severely suffered as they showed loss of integrity, marked irregularity and intense degenerative structural changes. Leydig cells were also suffering from some changes in the form of distorted shape nucleus, multiple vacuoles and damaged mitochondria. With rehabilitation there was different degrees of improvement in the shape of some seminiferous tubules and arrangement of their germinal epithelial cells with decrease in signs of degeneration. Other tubules were still suffering from the damaging effects of CP. This current study confirms the toxic effect of CP on the testicular tissue in the form of morphological and degenerative alterations in the germ cells and supported the reversibility of these effects. In addition, the present data proved that a potential recovery in spermatogenesis and testicular function levels to normal is appreciated with time of rehabilitation period after stopping the drug treatment