Effect of cyclophosphamide on the immature rat ovary.

To investigate the early ovarian changes after cyclophosphamide treatment, immature rats primed for 48 h with pregnant mare serum gonadotropin were given injections i.p. of cyclophosphamide (100 mg/kg) at 1, 2, 4, 16, and 24 h before decapitation. Serum estradiol dropped significantly after 24 h of exposure to cyclophosphamide (P less than 0.001). Following 16 and 24 h of cyclophosphamide exposure, (a) the number of granulosa cells expressed from each ovary decreased (P less than 0.05 and P less than 0.01, respectively); (b) the number of nucleated bone marrow cells decreased (P less than 0.01 and P less than 0.01), and their median nuclear size was significantly reduced (P less than 0.05 and P less than 0.05) as measured by Coulter Counter and C-256 channelyzer (Hialeah, FL); and (c) the mean follicular diameter and the number of follicles with diameters greater than 300 microns were significantly lower than in control. After 4, 16, and 24 h of exposure, median granulosa cell nuclear size significantly increased (P less than 0.05, P less than 0.01, and P less than 0.01, respectively). DNA cross-links in granulosa cells, measured by alkaline elution, reached a maximum at 2 h of exposure and decreased thereafter. The above findings demonstrate that cyclophosphamide has significant effects on the rat ovary structure and function and that the granulosa cell is an important target of cyclophosphamide-induced ovarian toxicity.