CONTRACEPTION W/ MINI DOSE ANTIPROGESTIN IN RHESUS MONKEYS

使用小剂量抗孕激素对恒河猴进行避孕

• 批准号: 6592336
• 负责人: Mary B Zelinski
• 金额: $ 11.11万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6592336
• 关键词: Mammalia; animal tissue; behavioral /social science research tag; clinical research; endocrine gland /system; hormones; model design /development; mother /infant health care; pharmacology; psychology; reproductive system; technology /technique; women's health

We recently determined that continual administration of low doses of the antiprogestin ZK 137 316 (Schering AG) to adult, female rhesus monkeys permits ovarian/menstrual cyclicity, but disrupts the growth and differentiation of the uterine endometrium. To determine if these (or other) changes in the reproductive tract are sufficient to prevent fertility (intrauterine pregnancy), female macaques (n=10/group) were treated daily with vehicle (controls), 0.01 or 0.03 mg ZK 137 316/kg body weight before and during 5 months of continual cohabitation with males of proven fertility. Mating behavior was confirmed by visual observation, and ejaculation occurred judged by the detection of sperm in the vagina. A cumulative pregnancy rate of 90% (9 of 10) was observed in controls. Of the animals receiving 0.01 mg/kg, 40% (4 of 10) conceived, with all conceptions occurring in the first 2 months of pairing. No pregnancies (0%, 0 of 10) occurred in the 0.03 mg/kg group. Although timely menstrual cyclicity occurred more frequently in the 0.01 mg/kg- than the 0.03 mg/kg-treated animals, ovarian cyclicity as judged from the observation of a corpus luteum on the ovaries was observed in both groups. Blood indices of circulating ions, liver function and blood cell constituents revealed no significant effects of chronic treatment. General toxicologic evaluation of major organs and tissues, either at a gross or microscopic level, did not identify any treatment-related changes. Thus, chronic administration of low dose antiprogestin prevents pregnancy in nonhuman primates, while permitting ovarian cyclicity and a high incidence of regular menstruation. Future studies are planned to determine the site(s) and mechanism(s) of contraceptive action of low-dose antiprogestin, e.g., in the uterus to prevent gamete transport or implantation. Also, experiments will examine whether the anti-fertility effects of ZK 137 316 are reversible. If so, this novel regimen of antiprogestin can be pursued as a potential contraceptive for women. RELEVANT PUBLICATIONS Zelinski-Wooten MB, Slayden OD, Chwalisz K, Hess DL, Brenner RM, Stouffer RL. Chronic treatment of female rhesus monkeys with low doses of the antiprogestin ZK 137 316 Establishment of a regimen that permits normal menstrual cyclicity. Hum Reprod, in press. Slayden OD, Zelinski-Wooten MB, Chwalisz K, Stouffer RL, Brenner RM. Chronic treatment of cycling rhesus monkeys with low doses of the antiprogestin ZK 137 316 Morphometric assessment of the uterus and oviduct. Hum Reprod, in press.

我们最近确定不断的低剂量给药 对抗植物 猴子允许卵巢/月经循环，但破坏了增长 子宫内膜的分化。 确定这些是否 （或其他）生殖道的变化足以防止 生育能力（宫内怀孕），雌性猕猴（n = 10/组）为 每天用车辆（对照组）处理0.01或0.03 mg ZK 137 316/kg 在5个月持续同居的5个月前体重与 雄性的生育能力。 交配行为通过视觉确认 观察和射精是通过检测精子来判断的 在阴道中。 累积怀孕率为90％（10中的9个）为 在对照中观察到。 在接受0.01 mg/kg的动物中，40％（4个 10）构思，所有概念都发生在 配对。 在0.03 mg/kg中没有怀孕（0％，10中的0）发生 团体。 尽管及时的月经循环发生更频繁地发生 在0.01 mg/kg-中，比0.03 mg/kg处理的动物，卵巢 从观察叶酸属肠上判断的环状 两组都观察到卵巢。 循环的血液指数 离子，肝功能和血细胞成分揭示了没有 慢性治疗的显着影响。 一般毒理学 评估主要器官和组织，无论是在总处或 显微镜水平，未识别任何与治疗相关的变化。 因此，长剂量抗植物的长期给药可防止 非人类灵长类动物的怀孕，同时允许卵巢循环和 常规月经的高发病率。 计划未来的研究 确定避孕作用的位置和机制 低剂量抗植物，例如在子宫中以防止配子 运输或植入。 另外，实验将检查是否 ZK 137 316的抗毛发效应是可逆的。 如果是这样，这个 可以将抗植物的新型疗法作为潜力。 女性的避孕药。 相关出版物Zelinski-Wooten MB， Slayden OD，Chwalisz K，Hess DL，Brenner RM，Stouffer RL。 慢性的 与低剂量的抗植物的雌性恒河猴的治疗 ZK 137 316建立一种允许正常月经的方案 循环。 嗡嗡作响，印刷中。 Slayden OD，Zelinski-Wooten MB， Chwalisz K，Stouffer RL，Brenner RM。 骑自行车的慢性治疗 低剂量的抗植物ZK 137 316的恒河猴猴子 子宫和输卵管的形态评估。 嗡嗡声复制，在 按。