A single dose of mifepristone induces ovulation in pseudopregnant rats

We used mifepristone (M) to evaluate the role of progesterone in maintaining pseudopregnancy. Cycling rats were made pseudopregnant (psp) by cervico-vaginal stimulation (CVS) on the day of estrus (day 0) and received 10 mg/kg M or vehicle (control groups) on day 3. Blood samples were taken at 06.00 h on days 4, 6 or 7 or at 18.00 h on days 3, 4, 6 or 10. M induced proestrus 2 days later (day 5), estrus on day 6, and a second prolonged diestrus afterwards. Prolactin and progesterone levels were similar in the control and M treated groups excepting on day 6, when both were reduced in the M-treated animals, and these rats were in estrus, suggesting a temporary impairment of luteal function. To demonstrate activated corpora lutea the endometrium was scratched on the fourth day of the first or second diestrus in additional control and M-treated groups. The deciduomal response was seen in the control and M groups after scratching the endometrium on day 4 of the first or second diestrus, respectively, but M blocked the deciduomal response in the first diestrus. Ovulation was confirmed by finding that 66.7% of the M-treated rats showed ova in the Fallopian tubes on the M-induced estrus and 4 out of 10 of the M rats placed with males on the M-induced proestrus showed spermatozoa in the vaginal smears. Half of these became pregnant, delivering 2 pups each. The results show that M can induce ovulation in psp rats, demonstrating that the anovulation observed after CVS is dependent on progesterone, yet luteal function persists after M in pseudopregnancy. Progesterone may act either by suppressing LH secretion or by permitting prolactin secretion, or both. Moreover, progesterone is required to maintain endometrial responsiveness.