A gonadotropin-releasing hormone agonist for the prevention of docetaxel-induced gonadal damage

초록

This study aimed to evaluate the protective effect of a gonadotropin-releasing hormone (GnRH) agonist against docetaxel-induced gonadotoxicity in a mouse model. Forty mice (female B6, 6-8weeks old, weighing 16-18g) were divided randomly into four groups. Groups 1 and 2 were treated with a single intraperitoneal dose of 0.1mL normal saline; Groups 3 and 4 received 30mg/kg docetaxel. Groups 2 and 4 were pre-treated with a subcutaneous injection of 0.3mg leuprolide acetate, 2weeks before the administration of docetaxel. The ovaries were removed 6weeks after docetaxel or saline injection. Total follicle number decreased in Group 3 compared to Group 1. There was a significant difference between the Groups 3 and 4 in the total follicle number. Many ovarian follicles were stained for Ki-67 in Groups 1, 2, and 4; however, in Group 3, only a small number were stained and destruction of the ovarian structure was observed. There was no immunohistochemistry staining with -H2AX in Groups 1, 2, and 4. However, -H2AX staining of the primordial follicles was observed in Group 3. GnRH agonists may protect ovarian follicles from docetaxel-induced ovarian damage considering the total follicle number, follicle proliferation, and double-strand DNA breaks.Impact statementProtection of the ovarian reserve and prevention of infertility are the primary quality of life issues in young cancer patients. In this study, ovarian suppression by gonadotropin-releasing hormone agonists protected ovarian follicles from docetaxel-induced ovarian damage considering the total follicle number, follicle proliferation, and double-strand DNA break.The findings of our study will provide useful information for fertility preservation in women with cancer, undergoing chemotherapy with docetaxel.

키워드