Human Reproduction, Vol 13, 269-277, Copyright © 1998 by Oxford University Press
OD Slayden, MB Zelinski-Wooten, K Chwalisz, RL Stouffer and RM Brenner
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.
ARTICLES
Chronic treatment of cycling rhesus monkeys with low doses of the antiprogestin ZK 137 316: morphometric assessment of the uterus and oviduct
Division of Reproductive Sciences, Oregon Regional Primate Research Center, Beaverton 97006, USA.
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