Kaplan-Kraicer R, Kostovetsky I, Bardin C W, Shalgi R
Department of Embryology, Sackler School of Medicine, Tel Aviv University, Israel.
Contraception. 1996 Jun;53(6):367-73. doi: 10.1016/0010-7824(96)00087-x.
Tamoxifen is a non-steroidal antiestrogen that possesses antagonistic as well a agonistic properties, while RU39411 is an antiestrogen that is known to possess only antagonistic properties. These steroid antagonists were administered orally to rats, with or without mifepristone, an antiprogestational agent, prior to implantation on Day 2 of pregnancy. The status of pregnancy was assessed on Day 14. Low doses of tamoxifen reduced litter size and weight and inducing embryonic absorption in some animals; a dose of 0.25 mg/Kg prevented pregnancy in all animals. RU39411 also had a dose-dependent effect on pregnancy, but a higher dose (0.5 mg/Kg) was required to achieve the same degree of pregnancy prevention. Addition of mifepristone to both antiestrogens had a synergistic effect on reducing litter size and weight. To determine the mechanism by which antiestrogens terminate pregnancy in rats, oviducts and uteri of treated rats were examined for the presence of embryos on Day 3 and 4 of pregnancy, times when most embryos would be expected to be in the oviducts. Most of the embryos of the treated animals were found in the oviducts on Day 3 of pregnancy. By Day 4, only a few embryos were still present in oviducts. These observations suggest acceleration of embryo transport by Day 4 of pregnancy. There was no accumulation of embryos in the uterus. Since acceleration of embryo transport through the reproductive tract in rat is induced by low doses of estrogens, it is likely that the agonistic action of tamoxifen is responsible for pregnancy prevention in these experiments. The fact that RU39411 also prevents pregnancy by a similar mechanism suggests that this estrogen antagonist also has some estrogen agonist effects on the oviduct. The fact that both antiestrogens also affected embryo weight could suggest the action of the antihormones on other mechanisms controlling embryo development.
他莫昔芬是一种非甾体类抗雌激素药物，具有拮抗和激动特性，而RU39411是一种已知仅具有拮抗特性的抗雌激素药物。在妊娠第2天植入前，将这些类固醇拮抗剂口服给予大鼠，同时给予或不给予抗孕激素药物米非司酮。在第14天评估妊娠状态。低剂量的他莫昔芬可减少窝仔数和体重，并在一些动物中诱导胚胎吸收；0.25mg/Kg的剂量可使所有动物妊娠终止。RU39411对妊娠也有剂量依赖性影响，但需要更高剂量（0.5mg/Kg）才能达到相同程度的妊娠预防效果。在两种抗雌激素药物中添加米非司酮对减少窝仔数和体重具有协同作用。为了确定抗雌激素药物终止大鼠妊娠的机制，在妊娠第3天和第4天检查处理过的大鼠的输卵管和子宫中是否存在胚胎，这两个时期大多数胚胎预计会在输卵管中。在妊娠第3天，处理过的动物的大多数胚胎在输卵管中被发现。到第4天，输卵管中仅存在少数胚胎。这些观察结果表明，在妊娠第4天时胚胎运输加速。子宫中没有胚胎聚集。由于低剂量雌激素可诱导大鼠生殖道中胚胎运输加速，因此在这些实验中，他莫昔芬的激动作用可能是妊娠终止的原因。RU39411也通过类似机制预防妊娠这一事实表明，这种雌激素拮抗剂对输卵管也有一些雌激素激动作用。两种抗雌激素药物都影响胚胎体重这一事实可能表明抗激素对控制胚胎发育的其他机制有作用。
