Chronic treatment of cycling rhesus monkeys with low doses of the antiprogestin ZK 137 316: morphometric assessment of the uterus and oviduct.
Chronic treatment of cycling rhesus monkeys with low doses of the antiprogestin ZK 137 316: morphometric assessment of the uterus and oviduct.
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DOI：
10.1093/humrep/13.2.269
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发表时间：
1998-02
影响因子：
6.1
通讯作者：
O. Slayden;M. Zelinski-Wooten;Krzysztof Chwalisz;R. Stouffer;Robert M. Brenner
中科院分区：
文献类型：
--
作者：
O. Slayden;M. Zelinski-Wooten;Krzysztof Chwalisz;R. Stouffer;Robert M. Brenner
研究了抗孕酮ZK 137 316对恒河猴生殖道形态的长期影响。每天（i.m.）给予溶媒或0.01、0.03或0.1 mg ZK 137 316/kg体重，持续5个月经周期。在对照组、0.01和0.03 mg/kg组的第5个周期的黄体中期（第8天）或0.1 mg/kg组的雌二醇峰值后6-7天采集生殖道（n = 3/组）。ZK 137 316治疗导致剂量依赖性子宫内膜萎缩，其特征为腺体有丝分裂活性降低、基质致密化、螺旋动脉降解和静脉扩张。ZK 137 316对子宫肌层或输卵管重量无影响。0.1和0.03 mg/kg（而非0.01 mg/kg）处理导致完全纤毛和分泌性输卵管，表明孕酮拮抗雌激素依赖性输卵管分化的剂量依赖性阻断。在子宫内膜中，孕酮对雌激素和孕酮受体的抑制作用也被ZK 137 316以剂量依赖性方式阻断。然而，子宫内膜萎缩出现由于抑制孕激素的作用，连同阻断雌激素依赖性增殖。长期低剂量ZK 137 316治疗产生的深度抑制的子宫内膜不太可能支持着床。因此，这种治疗可能提供一种新的避孕方式。
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.