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

O. D. Slayden, M. B. Zelinski-Wooten, K. Chwalisz, R. L. Stouffer, R. M. Brenner

    Research output: Contribution to journalArticle

    86 Scopus citations

    Abstract

    The long-term effects of the antiprogestin ZK 137 316 on reproductive tract morphology in rhesus macaques were investigated. The monkeys were 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 fifth 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 resulted 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 137 316 on myometrial or oviductal weight. Treatment with 0.1 and 0.03 mg/kg, but not 0.01 mg/kg resulted in fully ciliated and secretory oviducts, 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 receptors was also blocked by ZK 137 316 in a dose-dependent manner. However, endometrial atrophy appeared due to inhibition of progesterone action 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.

    Original languageEnglish (US)
    Pages (from-to)269-277
    Number of pages9
    JournalHuman Reproduction
    Volume13
    Issue number2
    DOIs
    StatePublished - Jan 1 1998

    Keywords

    • Antiprogestin
    • Antiproliferative
    • Endometrium
    • Macaque
    • Oestrogen action

    ASJC Scopus subject areas

    • Reproductive Medicine
    • Obstetrics and Gynecology

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