Prenatal Effect of Methotrexate Exposure on the Fetal Brain of Albino Rats and the Possible Protective Role of Folic Acid

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Background: Methotrexate is a folate antagonist, used to treat several diseases by interfering with cell growth. The objective of this study was to evaluate the effect of methotrexate on rat fetal telencephalon and the protective role of folic acid. Methods: 20 Pregnant rats weighting 200 – 250 gm were divided into four equal groups; control negative group, control positive group: received 60 mg/kg folic acid daily via gastric gavage from the first gestational day. Methotrexate treated group which treated with a single dose of 30 mg/kg methotrexate at gestation day 16. Methotrexate and folic acid treated group: received combined methotrexate and folic acid by the same manner mentioned before. The pregnant females were sacrificed over 2 gestational days (17thand 19th). The cerebrum was excised from each embryo, gross measurements were taken then processed for hematoxylin and eosin and caspase-3 staining for light microscopic examination. Results: Weight, volume, anteroposterior and transverse diameters of total cerebrum in methotrexate group were decreased in comparison to the control group. Histopathological examination revealed distributed vacuolated cells, hemorrhagic spots and congested blood vessels with in meninges in methotrexate treated group. Caspase-3 was widely expressed in fetal telencephalon in day 19 of methotrexate treated group in when compared with control group. All these findings were considerably improved in the combined methotrexate and folic acid treated group. Conclusions: Methotrexate induces microcephaly and apoptosis in the fetal telencephalon which is partially improved by folic acid supplementation

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Zagazig University Medical Journal
Volume 25, Issue 5
September 2019
Pages 689-698

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