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: 6116156
• 负责人: Mary B Zelinski
• 金额: $ 9.03万
• 依托单位: OREGON REGIONAL PRIMATE RESEARCH CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-15 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6116156
• 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，持续给予低剂量 的抗白细胞介素ZK 137 316（Schering AG）对成年雌性恒河猴 猴子允许卵巢/月经周期，但破坏生长 和子宫内膜的分化。 为了确定这些 (or其他）生殖道的变化足以防止 生育力（宫内妊娠），雌性猕猴（n=10只/组） 每日给予溶剂（对照），0.01或0.03 mg ZK 137 316/kg 连续同居5个月前和期间的体重 有生育能力的男性 交配行为通过目视检查确认 观察，并通过检测精子判断是否发生射精 在阴道里 累积妊娠率为90%（9/10）， 在对照组中观察到。 在接受0.01 mg/kg的动物中，40%（4只 10)怀孕，所有概念发生在前2个月， 配对 0.03 mg/kg组未发生妊娠（0%，0/10） 组 虽然及时月经周期发生更频繁 0.01 mg/kg组动物的卵巢 周期性判断从观察黄体上的 两组均观察卵巢。 循环血液指标 离子，肝功能和血细胞成分显示， 慢性治疗效果显著。 一般毒理学 主要器官和组织的评价，无论是在一个总的或 显微镜水平，未发现任何给药相关变化。 因此，长期给予低剂量的抗胰蛋白酶抑制剂可防止 非人灵长类动物妊娠，同时允许卵巢周期性， 月经规律发生率高。 未来的研究计划 确定避孕作用的部位和机制 低剂量抗孕酮，例如，在子宫里防止配子 运输或植入。 此外，实验将检查是否 ZK 137 316的抗生育作用是可逆的。 如果是这样， 新的抗孕酮治疗方案可以作为一种潜在的 女性避孕药。 相关出版物Zelinski-Wooten MB， Slayden OD，Chwalisz K，Hess DL，Brenner RM，Stouffer RL. 慢性 用低剂量的抗黑素蛋白治疗雌性恒河猴 ZK 137 316建立允许正常月经的方案 周期性 Reprod，in press. Slayden OD，Zelinski-Wooten MB， Chwalisz K，Stouffer RL，Brenner RM. 慢性治疗骑自行车 恒河猴与低剂量的抗白细胞介素ZK 137 316 子宫和输卵管的形态测量评估。 Reprod，in press.