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Abstract

EFFECTS OF LOW DOSE OF METHRATAXATE (MTX) ON WEIGHT, STILLBIRTH (INTRAUTERINE DEATH) OF MICE EMBRYOS AND HISTOLOGICAL STUDY OF EMBRYONIC BRAIN

*Ban Thabit Al-Ani, Mohammad Oda Salman: MBChB, FIBMS (CAA) and
Rana R. Al-Saadi

ABSTRACT

Background: MTX a medicine stop growth of cells and interfere with immune system. Its efficacy is wide but it may cause serious or lifethreatening toxicities on liver, lungs, kidney and immune system. In humans, a severe malformation called the “aminopterin syndrome” has been described in outcomes of pregnancies exposed to MTX from four to 12 weeks. This syndrome consists of CNS abnormalities (spina bifida, mental retardation, hydrocephaly, anencephaly). Closed neural tubes but poor brain development were seen in rat embryos cultured on folate-deficient serum, and neural tube defects have been demonstrated in embryos of folic-acid-deficient rats. The Objective is to Observed the effect of low dose MTX on weight, mortality rate and the toxic effect of MTX on the brain of mice embryos. A group of pregnant female mice (10 pregnant mice) injected by low dose MTX (0.02 mg/kg), at day 4, 5, 6 of gestation (G1), another (10 pregnant mice) injected by the same dose of MTX day 14, 15, 16 (G2). Four pregnant female mice served as a control group. Pregnant females were sacrificed on gestational day 7, 17 then examine the embryos weight and the incidence of intrauterine death. For histological study 20 mice embryos were fixed in Bouin fixative, paraffin infiltration, then embedded sections stained with haematoxylin and eosin, the specimens independently read. The Results shows a highly significant decrease in weight of embryos at days 7, 17 (P< 0.01) as comparison with control groups. None of embryos died in control group, there is a highly significant increase in mortality rate were observed in G1, G2(P<0.05). And 60% of embryos died at day 7 and 30% of embryos died at day 17. The histological investigation showing embryonic brain damage in all brain regions. In Conclusion low dose MTX discontinued as early as possible in pregnant women because of its toxic effect on embryos.

Keywords: Methotrexate, embryo, weight, intrauterine death, brain toxicity.


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