Methotrexate(4-amino-N10-methyl pteroyl glutamic acid) 투여가 수태백서태반에 미치는 영향에 관한 병리조직학적 연구

Abstract

Methotrexate is an anticancerous drug used most commonly in trophoblastic disease especially in choriocarcinoma by its antifolic acid effects. But its effects on the normal placenta was not well known. To see the effects of methotrexate on the normal trophoblasts and its stroma following experiment was carried out with 135 Sprague'Dawley rats. Experimental group were divided by 45 rats of preterm placenta group and 90 rats of term placenta groups. Preterm placenta group was subdivided into fifteen small groups by its dosage (0.1 to 0.4mg MTX) and date of administration of methotrexate. Preterm placenta group was sacrificed at 8th, l Ith, and 15th day those were one day after methotrexate administration. Term placenta group was sacrificed at term (20th day) after methotrexate administration at 7th, 10th and 14th day with one third dosage of total amount in each day by oral intubation. Placentae were examined histopathologically and histochemically with alkaline phosphatase, acid phosphatase, NADH diaphorase and succinic dehydrogenase stainings, Results obtained were as follows: 1. Wastage rates after methotrexate administration revealed that no wastage was seen in control rats but experimental groups showed 7.8% (group I, 0.15mg MTX) , 33.8% (n, 0.3mg MTX), 62.2% (ill, O. 6mg MTX), 88. 7%(N, 0.9mg MTX), 96.8% (V, 1. 2mg MTX), 94.4% (\1, 1. 5mg MTX), 94.0 % (W, 1. 8mg MTX) , 100% (IIII, 2. 1mg MTX) and 100% (lX, 2.4mg MTX). The wastage rates were increased as dosage of methotrexate was increased. 2. Histopathological study of pre term placenta group revealed that no specific changes in 8th day of gestation, mild and focal hemorrahge in 11th day placenta and focal fibrinoid necrosis in labyrinth and base were seen in the group N (0. 4mg MTX) accompanying mild cytolysis of glycogen cells. Alkaline phosphatase and NADH diaphorase activities were slightly decreased but activities of acid phosphatase and succinic dehydrogenase were not decreased. 3. Histophathological study of term placenta groups revealed mild congestion and fibrinoid necrosis and increased desposits of fibrinous materials in the basal zone in group I ~ ill (0. 15~0. 6mg MTX), increased hemorrhage and fibrinoid necrosis as well as resorbed placentae in groups N~W (0. 9mg~ 1. 8mg MTX) and all resorbed placentae were in group IIII~ lX (2. 1mg~2. 4mg MTX). Histochemically alkaline phosphatase activity was slightly increased in the labyrinth and basophilic cells of base. Acid phosphatase activity was increased in the basophilic cells of base. NADH diaphorase activity was slightly decreased in the labyrinth but succinic dehydrogenase activity was not decreased. 4. Therefore, with above features administration of methotrexate was related to the abortion and wastage rate of pregnancy and the first histological findings were seen in the labyrinth and basal zone showing decreased activities of alkaline phosphatase and NADH diaphorase with focal necrosis and hemorrhage followed by complete fibrinoid necrois and absorption of placenta.