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Methotrexate(4-amino-N10-methyl pteroyl glutamic acid) 투여가 수태백서태반에 미치는 영향에 관한 병리조직학적 연구 : Histopathological Study on Effects of Methotrexate (4-amino-Nlo-methyl pteroyl glutamic Acid) Administration in Rat Placentae

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이인철; 함의근; 송계용; 장자준

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서울대학교 의과대학
Seoul J Med, Vol.23 No.4, pp. 411-423
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.
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