Effects of progesterone antagonists RU486 and ZK98734 on embryo transport, development and implantation in laboratory mice.

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.