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 tract morphology in rhesus macaques were investigated, The monkeys wer e injected daily (i.m.) for five menstrual cycles with vehicle or 0.01 , 0.03 or 0.1 mg ZK 137 316/kg body weight, Reproductive tracts (n = 3 /group) were collected during the mid-luteal phase (day 8) of the fift h cycle in the control, 0.01 and 0.03 mg/kg groups, or 6-7 days after the oestradiol peak in the 0.1 mg/kg group, ZK 137 316 treatment resul ted in a dose-dependent atrophy of the endometrium, marked by reduced mitotic activity in the glands, compaction of the stroma, degradation of spiral arteries and dilation of veins, There was no effect of ZK 13 7 316 on myometrial or oviductal weight, Treatment with 0.1 and 0.03 m g/kg, but not 0.01 mg/kg resulted in fully ciliated and secretory ovid ucts, indicating a dose-dependent blockade of progesterone antagonism of oestrogen-dependent oviductal differentiation. In the endometrium, the suppressive action of progesterone on oestrogen and progestin rece ptors was also blocked by ZK 137 316 in a dose-dependent manner, Howev er, endometrial atrophy appeared due to inhibition of progesterone act ion together with a blockade of oestrogen-dependent proliferation, The profoundly suppressed endometrium produced by chronic low-dose ZK 137 316 treatment is unlikely to support implantation, Such treatment may therefore provide a novel contraceptive modality.