Effect of Cyclophosphamide on the Postnatal Development of the Ovary of the Albino Rat

Background: Cyclophosphamide is the most widely used alkylating agent in the treatment of haematological malignancies. On the other hand, cyclophosphamide has adverse effects on the fertility of both sexes.   Aim of the work: The present work was done to study the histological and stereological changes in the developing ovary of the albino rat after a period of treatment with cyclophosphamide and the effect of rehabilitation after stopping the drug. Materials and Methods: Thirty-six immature female rats (newborn, one week, two weeks, oneand-half month and two- and-half month) were used in this study. They were subdivided into two groups. The control group (n=24) was injected intraperitoneally with dextrose 5%. The experimental group (n= 12) at the age of two weeks, received 100mg/ kg body weight cyclophosphamide intraperitoneally once weekly for four successive weeks. At the end of the treatment period this group was subdivided into two subgroups: subgroup A (treated group) including the rats at the age of one- and- half month and subgroup B (rehabilitated group) including  the rats at the age of two-and-half month which received the same drug regimen, but sacrificed after another four weeks without treatment.  The specimens of all age groups were processed and stained with Heamatoxylin and Eosin. Other specimens at the age of one- and- half month were processed for semi-thin and ultra-thin examination. In the two age groups (control and treated) morphometeric measurements were performed. Results: The study showed shrinkage with decrease in the number and the size of the antral follicles, apoptosis and disorganization in the granulosa cell layers.  Ultrastucturally, the most important feature observed was the fragmentation and leakage of the cellular nuclear materials of the granulosa cells and their clumping in the antrum. Morphometeric measurements showed a very highly significant reduction in the average follicular and oocytic diameter of the antral follicles and in the number of the healthy antral follicles while there was high significant reduction in the number of atretic antral follicles. In the rehabilitated group the follicles were less affected. Oocytes were affected in both groups; they were either vacuolated or totally absent. Morphometeric measurements showed highly significant reduction of the average oocytic diameter and in the average number of the granulosa cell layers