Morphological and immunohistochemical analysis in ovaries and fallopian tubes of tamoxifen, letrozole and clomiphene-treated rats

Ovarian and tubal dysplasia may be precursors to ovarian cancer. The goal of this study was to check whether these histopathological lesions would be found after ovulation induction using tamoxifen, clomiphene citrate and letrozole. Seventy-two rats were divided into four groups. In the first group, 24 rats received normal saline. The second group (16 rats) received clomiphene citrate for six cycles. The third group, divided into two sub-groups of eight rats each, were stimulated with tamoxifen for six cycles, with a dosage, respectively, of 0.4 and 0.8 mg/kg/day. In the last group, eight rats received letrozole 0.1 mg/kg/day and eight other rats received letrozole 0.5 mg/kg/day, for six cycles. Once the six cycles had been completed the rats were killed in order to remove ovaries and tubes for histopathological analysis (morphological, p53 and Ki67 immunohistochemical assessment). Histopathological lesions were found in both ovaries and tubes. The mean ovarian dysplasia score was significantly higher in the tamoxifen group whatever the dosage (p = 0.006 and 0.0002) and in the letrozole group with 0.5 mg/kg/day (p = 0.0002) compared with the control group. The mean tubal dysplasia score was significantly higher in all groups that received drug treatment compared with the control group, whatever the dosage used. The proliferation index (Ki67) was significantly higher in the tamoxifen and letrozole groups while no significant difference was found for apoptosis marker p53. Ovulation induction may induce histopathological abnormalities in ovaries and tubes with a different immunohistochemical profile in comparison with salpingo-oophorectomies for genetic risk.