The Protective Effect of GnRH Agonist Triptorelin on the Histomorphometric Parameters of the Utero-ovarian Tissue in the Doxorubicin- and Cyclophosphamide-treated Mice.

Abstract

One of the common side effects of chemotherapy drugs is ovarian failure and uterine dysfunction, which can occur after the administration of doxorubicin and/or cyclophosphamide. In clinics, gonadotropin-releasing hormone agonists (GnRHa) are used to modulate the toxic effect of chemotherapy and intercept infertility with some controversy and limited histological knowledge. This study aimed to evaluate the serological and histological features of protective effects of triptorelin, (GnRHa), on utero-ovarian tissue in the mice treated with cyclophosphamide and/or doxorubicin. Forty-eight female BALB/c mice were randomly divided into 8 groups as follows: Group I: normal saline; Group II: triptorelin; Group III: cyclophosphamide; Group IV: doxorubicin; Group V: cyclophosphamide + doxorubicin; and Groups VI, VII, and VIII: after injection of cyclophosphamide, doxorubicin, or cyclophosphamide + doxorubicin, administration of triptorelin (1 mg/kg; intraperitoneally) for 15 consecutive days, respectively. On the 21st day, the ovaries and uterine horns were dissected and weighed. Then, tissue processing and staining were performed for further histological and stereological studies. Triptorelin treatment in the damaged groups significantly increased the number of primordial and pre-antral follicles and granulosa cells. It decreased the number of atretic follicles compared to cyclophosphamide and/or doxorubicin-treated groups (P < 0.05). Triptorelin also significantly improved the volume of the ovary, cortex, medulla, oocytes in the primordial and antral follicles, uterus, endometrium, myometrium, uterine glands, and endometrial blood vessels in the damaged groups (P < 0.05). Triptorelin treatment prevents the destructive effects of cyclophosphamide and/or doxorubicin on utero-ovarian tissue.