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Effect of Cyclophosphamide on the Immature Rat Ovary¹

Department of Obstetrics and Gynecology [K. M. A., A. J. R-A.] and Department of Medicine [F. A. V.], Wayne State University, Detroit, Michigan 48201

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 < 0.001). Following 16 and 24 h of cyclophosphamide exposure, (a) the number of granulosa cells expressed from each ovary decreased (P < 0.05 and P < 0.01, respectively); (b) the number of nucleated bone marrow cells decreased (P < 0.01 and P < 0.01), and their median nuclear size was significantly reduced (P < 0.05 and P < 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 µm were significantly lower than in control. After 4, 16, and 24 h of exposure, median granulosa cell nuclear size significantly increased (P < 0.05, P < 0.01, and P < 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.

¹ This research was funded by the American Cancer Society (Grant CH-365), Wayne State University Institute of Chemical Toxicology, and Children's Leukemia Foundation of Michigan.

² To whom requests for reprints should be addressed, at Division of Reproductive Endocrinology and Infertility, Department of Obstetrics and Gynecology, Wayne State University, 275 East Hancock, Detroit, MI 48201.

Received 5/24/88. Revised 10/ 5/88. Revised 12/29/88. Accepted 1/ 4/89.

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