Local effects of mifepristone on the nonhuman primate endometrium.

Objective: To determine the effects of a low-dose mifepristone regimen on endometrium in the rhesus monkey by endometrial staging and analysis of molecular markers of endometrial receptivity.

Design: A prospective, randomized comparative study.

Setting: Academic research environment.

Animal(s): Normally cycling rhesus (Macaca mulatta) monkeys.

Intervention(s): Monkeys (5 per control or treatment group) received 0.03 mg of mifepristone in vehicle (sesame oil) per kilogram of body weight or vehicle daily from day 2 of the menstrual cycle to 7 days after the midcycle E2 surge.

Main Outcome Measure(s): Serum estradiol (E2) and progesterone (P) levels; endometrial staging and immunoreactivity of leukemia inhibitory factor and interleukin-6 performed on fixed endometrial tissues; and relative abundance of endometrial estrogen and P receptor mRNA evaluated with semiquantitative reverse transcriptase polymerase chain reaction in which cyclophilin mRNA, a housekeeping gene product, was coamplified as the reference standard.

Result(s): Mifepristone at 0.03 mg/kg/d induced a delay in the endometrial cycle with a shift from the late to midsecretory phase. This treatment regimen did not suppress the midcycle gonadotropin surge or, presumably, ovulation because P levels were normal during the midluteal phase. The staining intensity of leukemia inhibitory factor and interleukin-6 was dependent upon the endometrial stage and was decreased in treated monkeys. E and P receptor mRNAs increased significantly with mifepristone treatment compared with controls, another indication of delayed uterine staging.

Conclusion(s): Mifepristone at 0.03 mg/kg/d had no antiovulatory effect but delayed development of the endometrium from the late to midsecretory phase. This study provides further evidence that endometrial maturation can be altered without affecting ovarian cyclicity.