Human Reproduction, Vol 13, 1063-1069, Copyright © 1998 by Oxford University Press
JA DeLoia, AM Stewart-Akers and MD Creinin
Methotrexate is a folic acid analogue that has been used successfully for
the treatment of ectopic pregnancy and, in conjunction with misoprostol,
for medical abortions of early intrauterine pregnancies. To administer the
most efficacious treatment requires knowledge of the mechanism underlying
the induction of methotrexate-induced abortion. This study was designed to
ascertain trophoblast integrity, proliferation and differentiation
following administration of methotrexate. In addition, to determine if
methotrexate affects the local uterine immune response, we ascertained the
numbers and identities of decidual leukocytes following treatment. Ten
women with undesired intrauterine pregnancies of 42-49 days gestation were
recruited to receive methotrexte 50 mg/m2 i.m. A suction aspiration was
performed 7 days later. Tissues from gestational age-matched elective
surgical abortions were used as controls. Additionally, specimens from
women who received methotrexate and misoprostol for abortion in a clinical
trial of oral methotrexate in combination with misoprostol, who had a
suction abortion because of continued embryonic cardiac activity 14 days
after the methotrexate, were evaluated. Immunoreactivity to proliferating
cell nuclear antigen and cyclin D3 antibodies was used to demonstrate a
marked reduction in the proliferation index of cytotrophoblasts from
methotrexate-treated abortions. Methotrexate treatment failures and
non-treated pregnancies had a much higher proliferation index. There was no
direct destruction of the syncytiotrophoblast, as indicated by the
continued presence of human placental lactogen and beta-human chorionic
gonadotrophin proteins. A decrease in the total number of leukocyte cells
was observed in the decidua of methotrexate-treated samples, with the large
granular lymphocyte (LGL) cells showing the greatest decline in numbers.
Our conclusions from this study are that methotrexate acts primarily to
derail the normal developmental programme of the trophoblast stem cell
population, as well as to decrease LGL cell numbers in the decidua.
ARTICLES
Effects of methotrexate on trophoblast proliferation and local immune responses
Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, The Magee Women's Research Institute, PA 15213, USA.
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