Vinijsanun A, Martin L
Department of Physiology and Pharmacology, University of Queensland, St Lucia, Australia.
Reprod Fertil Dev. 1990;2(6):713-27. doi: 10.1071/rd9900713.
Two progesterone antagonists blocked the actions of progesterone on uterine mitosis and epithelial morphology, but had no oestrogenic, anti-oestrogenic, cytotoxic or gestagenic activities in the mouse uterus. They interrupted early pregnancy and were luteolytic. These actions were reversed by treatment with exogenous progestins, but not dexamethasone. Doses of antagonists which blocked pregnancy and were luteolytic induced premature entry of embryos into the uterus on Day 3 and loss from the tract by Day 4. With the more potent RU486, most embryos remaining in the tract on Day 4 were in the oviduct. This 'tube-locking' and accelerated loss were probably due to 'unopposed' actions of ovarian oestrogen. They were reversed by progestin treatment; this suggests that progesterone is essential for normal embryo transport. Doses of antagonists which prevented normal embryo transport and implantation had little effect on preimplantation embryo development. Small increases in numbers of abnormal embryos on Day 4 were not significant or dose dependent. Abnormalities were not correlated with location of embryos, nor prevented by progestin treatment which reversed antagonist effects on embryo transport and implantation. Hence, progesterone is apparently not essential for successful completion of preimplantation development of mouse embryos in vivo.
两种孕酮拮抗剂可阻断孕酮对子宫有丝分裂和上皮形态的作用，但在小鼠子宫中无雌激素、抗雌激素、细胞毒性或孕激素活性。它们可中断早期妊娠并具有溶黄体作用。这些作用可通过外源性孕激素治疗逆转，但地塞米松不能。阻断妊娠并具有溶黄体作用的拮抗剂剂量可导致胚胎在第3天提前进入子宫，并在第4天从生殖道排出。使用效力更强的RU486时，第4天仍留在生殖道的大多数胚胎位于输卵管。这种“输卵管滞留”和加速排出可能是由于卵巢雌激素的“无对抗”作用。它们可通过孕激素治疗逆转；这表明孕酮对于正常胚胎运输至关重要。阻止正常胚胎运输和着床的拮抗剂剂量对植入前胚胎发育影响很小。第4天异常胚胎数量的少量增加并不显著或无剂量依赖性。异常情况与胚胎位置无关，也不能通过逆转拮抗剂对胚胎运输和着床作用的孕激素治疗来预防。因此，孕酮显然对于小鼠胚胎在体内成功完成植入前发育并非必不可少。
