Morphological and morphometrical study of cyclophosphamide-induced changes in the ovary and uterus in the Syrian mice

The objective of this research was to evaluate the cause of fertility reduction after chemotherapy. Cyclophosphamide is a common chemotherapy and immunosuppressive agent used for the treatment of a wide range of neoplastic and some auto-immune diseases. In the present study, morphometrical changes in the ovary and uterus of 12 5–6-week-old female Syrian mice after intraperitoneal injection of 75 mg cyclophosphamide/kg BW were assessed. Control animals (n = 8) were injected with sterile distilled water using similar method. The results of this study revealed that cyclophosphamide eliminated almost more than 50% of the primordial follicles (PMF) reserve. The mean ± SE number of PMF in the control group was 1210 ± 135 compared to 464 ± 55 in the test group. The mean number of secondary, tertiary follicles and corpora lutea also showed significant (P<0.05) reduction in the treatment group. The histomorphometric studies also showed that the mean ± SE diameter of the ovary in the control group was 1703 ± 78 µm as compared to 900.9 ± 86 µm in the test group (P<0.01). The thickness of the uterine wall was also significantly different with a mean ± SE of 745.7 ± 13 µm in the control and 393.1 ± 23 µm in the test group. The mean ± SE thickness of endometrium in the control group was 392.1 ± 16 µm, whereas in the test group it was 194 ± 10 µm (P<0.001). The results of this study revealed that chemotherapy with cyclophosphamide causes destruction of PMF as well as other growing follicles; accordingly, the reproductive potential was negatively affected. The method used in this study can be most likely used as a sensitive and inexpensive tool to predict the damage to fertility caused by new chemotherapy protocols. In conclusion, chemotherapy brings about a) reduction in ovarian follicular populations, especially PMF, b) it causes reduction in diameter and size of ovary and c) decreases thickness of uterine wall, especially endometrium.