effect of methotrexate on the fallopian tubes of adult albino rats: a histological and immunohistochemical study

ABSTRACT

Methotrexate [Mtx] [the anticancer drug] has been a prevalent drug in the conservative treatment for unruptured tubal pregnancy for many years. Unfortunately, current emphasis has been on its damaging effects on the ovaries and fallopian tubes. The aim of this study was to examine the acute and long-term toxic effects of different doses of Mtx on the fallopian tubes. The study was carried out on 60 female rats. The rats were divided into three groups the control group [group I], comprising 20 rats; group II, comprising 20 rats given 2.5 mg/kg Mtx intraperitoneally for 10 days [acute study]; and group III, comprising 20 rats given 2.5 mg/kg Mtx for 2 months [long-term study]. Rats in each group were killed at each time point and the fallopian tubes were dissected and stained with H and E, following which estrogen receptor [ER] expression was detected by immunohistochemistry. Light microscopy [acute] study showed a decrease in the number of mucosal folds with fusions of some folds. Cellular infiltration was limited to the mucosa when Mtx was administered in small doses. With increasing dose of Mtx, cellular infiltration extended to the musculosa and serosal layer. In the chronic study some regions showed an improvement in epithelial folding and the muscle layer, together with a decrease in cellular infiltration, especially at low dose. The immunohistochemical study revealed a weak positive immunoreaction for ERs in all rats of the acute group and high-dose chronic group, whereas in the low-dose chronic study moderate positive reaction for ERs in epithelial cells was detected. These results prove that Mtx [>/=5 mg/kg] can induce long-term, irreversible damage to fallopian tubes and steroid hormone receptors [ER] in a dose-dependent manner. Therefore, Mtx should be used in a relatively small and safe range of dosage in order to avoid impairment and potential risk of subsequent tubal pregnancy or infertility