Effects of the progesterone antagonist RU486 on myometrial activity in vivo in early pregnant and pseudopregnant rats

Abstract

Myometrial activity in vivo was quantified by video-laparoscopy in early pregnant rats given doses of RU486 which caused embryo abortion and blocked the action of progesterone on the vagina. All treatments diminished the frequency of circular contractions and abolished the curling movements of the uterus which are characteristic of pregnant, pseudopregnant and progestin-treated rats. The effects of RU486 on circular contractions were similar in pseudopregnant rats, i.e. they were not a consequence of embryo abortion. These results support the thesis that increased myometrial circular contractions in early pregnancy and pseudopregnancy are induced by increasing levels of progesterone. Effects of RU486 on longitudinal contractions were more complex: the highest dose inhibited longitudinal contractions on Day 5 of pregnancy and pseudopregnancy, but increased their frequency on Day 6. The acute inhibition of longitudinal contractions by RU486 was unexpected and the mechanism remains to be elucidated. The later increase in the frequency of longitudinal contractions appears to be due to antagonism of progesterone by RU486. The frequency of caudal longitudinal contractions on Day 6 in mated rats given RU486 was similar to that in unmated oestrous rats, but the frequency of cranial longitudinal contractions was significantly higher. These results support the hypothesis that stimuli received during copulation may have long-term effects on myometrial activity, by increasing pacemaker activity at the cervix.