Methotrexate (MTX) is a common folate antagonist and it blocks the dihydrofolate reductase,thereby causing tetrahydrofolate formation disorder.Tetrahydrofolate is the active folate form and its related metabolic products are required for DNA synthesis and DNA methylation modification.The effects of MTX have been demonstrated by DNA methylation aberrations,DNA damage,and DNA synthesis obstruction,causing cell replication disorder and apoptosis [1,2].Since MTX passes through blood-brain,blood-testis,and blood-ocular barriers,high-dose MTX is commonly used to treat malignancies in clinic (the high dose generally is the total dosage of MTX ＞1 g once or single dose ＞20 mg/kg) [3].The main defect of MTX treatment is its insufficienttumor targeting because MTX kills cancer cells and at the same time also destroys the normal cells [2].Additionally,MTX has also been reported to reduce the oocyte quality [4].
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