Histological and immunohistochemical study of cyclophosphamide effect on adult rat testis

Abstract

Background: Nowadays, cyclophosphamide is widely used as anticancer and immunosuppressive agent in various drug regimens in many diseases and in young and old age. The aim of this research is to study the possible histological changes that may occur in the testes of adult male albino rats as a result of chronic exposure to cyclophosphamide and the prognosis of this effect. Methods: Thirty healthy adult male albino rats were used in this study.  They were equally divided into three groups; a control, an experimental and a withdrawal groups. The Animals of the experimental group were treated with daily dose of 5 mg/ kg cyclophosphamide orally for successive 28 days. Animals of the withdrawal group were left without treatment and sacrificed after 28 days from the last dose of cyclophosphamide.  At the time of sacrifice, all animals were anesthetized by ether inhalation and their testes were dissected out carefully and processed for light and electron microscope examinations. Results: Testes of the cyclophosphamide treated group revealed presence of many distorted shrunken seminiferous tubules which appeared with marked reduction in the thickness of the epithelium and wide lumina. Many germ cells with deeply stained nuclei, giant cells in mitosis and intracellular vacuoles were observed. Cross sections in mid pieces of sperms showed marked affection of axoneme, fibrous sheath and mitochondrial sheath. The cytoplasm of the Leydig cells contained mitochondria, dilated SER, Golgi cisternae and RER. Testes of the withdrawal group showed that the seminiferous tubules still had reduced height of their epithelium with wide intercellular spaces. Abnormal stratification and destructed germinal epithelium were evident with desquamated germ cells. Cross sections of mid pieces of the sperms showed distorted axoneme and swollen mitochondrial sheath. The cytoplasm of leydig cells contained many electron dense granules, RER, many dilated SER and mitochondria. Conclusions: Chronic cyclophosphamide treatment not only produced serious histological changes of the testis but also in its serological parameter. These changes persisted after cessation of cyclophosphamide administration which indicates the cumulative irreversible toxic effect of cyclophosphamide. So, it is advisable to avoid the usage of cyclophosphamide as possible especially in young patients.