DeLoia J A, Stewart-Akers A M, Creinin M D
Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, The Magee Women's Research Institute, PA 15213, USA.
Hum Reprod. 1998 Apr;13(4):1063-9. doi: 10.1093/humrep/13.4.1063.
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.
甲氨蝶呤是一种叶酸类似物，已成功用于治疗异位妊娠，并与米索前列醇联合用于早期宫内妊娠的药物流产。要进行最有效的治疗，需要了解甲氨蝶呤诱导流产的潜在机制。本研究旨在确定甲氨蝶呤给药后滋养层细胞的完整性、增殖和分化情况。此外，为了确定甲氨蝶呤是否影响局部子宫免疫反应，我们在治疗后确定了蜕膜白细胞的数量和类型。招募了10名妊娠42 - 49天的意外宫内妊娠妇女，接受50 mg/m²的甲氨蝶呤肌肉注射。7天后进行吸宫术。将与孕周匹配的选择性手术流产组织用作对照。此外，对在甲氨蝶呤联合米索前列醇口服的临床试验中接受甲氨蝶呤和米索前列醇流产的妇女的标本进行了评估，这些妇女在甲氨蝶呤给药14天后因胚胎持续心脏活动而进行了吸宫流产。使用增殖细胞核抗原和细胞周期蛋白D3抗体的免疫反应性来证明甲氨蝶呤治疗的流产中细胞滋养层细胞增殖指数显著降低。甲氨蝶呤治疗失败的病例和未治疗的妊娠增殖指数要高得多。人胎盘催乳素和β - 人绒毛膜促性腺激素蛋白持续存在表明合体滋养层没有直接被破坏。在甲氨蝶呤治疗的样本蜕膜中观察到白细胞总数减少，其中大颗粒淋巴细胞（LGL）数量下降最为明显。我们从这项研究中得出的结论是，甲氨蝶呤主要作用是扰乱滋养层干细胞群体的正常发育程序，并减少蜕膜中LGL细胞的数量。
