Chronic treatment of cycling rhesus monkeys with low doses of the antiprogestin ZK 137 316: morphometric assessment of the uterus and oviduct

The long-term effects of the antiprogestin ZK 137 316 on reproductive tractmorphology in rhesus macaques were investigated. The monkeys were injecteddaily (i.m.) for five menstrual cycles with vehicle or 0.01, 0.03 or 0.1 mgZK 137 316/kg body weight. Reproductive tracts (n = 3/ group) werecollected during the mid-luteal phase (day 8) of the fifth cycle in thecontrol, 0.01 and 0.03 mg/kg groups, or 6-7 days after the oestradiol peakin the 0.1 mg/kg group. ZK 137 316 treatment resulted in a dose-dependentatrophy of the endometrium, marked by reduced mitotic activity in theglands, compaction of the stroma, degradation of spiral arteries anddilation of veins. There was no effect of ZK 137 316 on myometrial oroviductal weight. Treatment with 0.1 and 0.03 mg/kg, but not 0.01 mg/kgresulted in fully ciliated and secretory oviducts, indicating adose-dependent blockade of progesterone antagonism of oestrogen-dependentoviductal differentiation. In the endometrium, the suppressive action ofprogesterone on oestrogen and progestin receptors was also blocked by ZK137 316 in a dose-dependent manner. However, endometrial atrophy appeareddue to inhibition of progesterone action together with a blockade ofoestrogen-dependent proliferation. The profoundly suppressed endometriumproduced by chronic low-dose ZK 137 316 treatment is unlikely to supportimplantation. Such treatment may therefore provide a novel contraceptivemodality.