Protective effect of gonadotropin-releasing hormone agonist on ovarian functional impairment caused by radiation in rats

Objective To investigate the protective effect of gonadotropin-releasing hormone agonist (GnRHa) on ovarian function in rats during pelvic irradiation and its possible mechanism. Methods 1. Five female Fischer-344 rats were subcutaneously injected with 0.25 mg of GnRHa. Changes in serum follicle-stimulating hormone(FSH), estradiol(E2), and anti-mullerian hormone(AMH) levels were observed continually. 2. Forty female rats were randomly divided into four groups(Control, GnRHa, R, and GnRHa+R) and given their corresponding treatments. At 20 days after pelvic irradiation, the weight; ovarian wet weight; serum FSH, E2, and AMH levels; and follicular numbers of the four groups were compared using one-way ANOVA and independent-sample t-test. The apoptotic index and microvessel density(MVD) in the ovarian tissue of each group were also compared. Results 1. Treatment with GnRHa inhibited ovarian function. Under this treatment, serum FSH and E2 declined, reached the minimum values in approximately 15 days, and then normalized in approximately 20 days. 2. After pelvic radiotherapy, the GnRHa+R and R groups showed different degrees of ovarian function damage compared with the control group, but the damage to the GnRHa+R group was less severe compared with that to the other groups. The GnRHa+R group showed higher E2(t= 12.79, P < 0.01), lower FSH(t= 4.65, P < 0.01), and relatively higher AMH (t= 5.65, P < 0.01) compared with the R group. Follicular classification revealed significantly more primordial and primary follicles in the GnRHa+R group than in the R group(t=7.70, P<0.01). Tunnel and CD31 staining showed that the apoptotic index and MVD were significantly higher in the R group than in the GnRHa+R group(t= 8.20 and 9.83, both P < 0.05). Conclusions Administration of GnRHa before radiotherapy can significantly decrease radiation damage to ovarian function in rats. GnRHa exerts its protective effect against ovarian functional impairment by inhibiting follicular development in primordial and primary follicles. It decreases the blood supply and oxygen of ovarian tissue, thereby reducing the radiation sensitivity of the ovary. Key words: Radiation tolerance; Radiotherapy; Ovary; Radiation protection; Gonadotropin-releasing hormone agonist