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，持续给予低剂量 抗孕激素 ZK 137 316 (Schering AG) 治疗成年雌性恒河猴 猴子允许卵巢/月经周期，但会破坏生长 以及子宫内膜的分化。 以确定是否有这些 （或其他）生殖道的变化足以预防 生育力（宫内妊娠），雌性猕猴（n=10/组） 每天用载体（对照）治疗，0.01 或 0.03 mg ZK 137 316/kg 连续同居前和同居 5 个月期间的体重 已证实具有生育能力的男性。 通过视觉确认交配行为 观察，通过检测精子来判断是否射精 在阴道里。 累计妊娠率为 90%（10 例中有 9 例） 在对照中观察到。 在接受 0.01 mg/kg 剂量的动物中，40%（4 只） 10) 受孕，所有受孕发生在出生后的头 2 个月内 配对。 0.03 mg/kg 剂量范围内未发生妊娠（0%，10 例中有 0 例） 团体。 虽然及时的月经周期发生的频率更高 0.01 mg/kg-比0.03 mg/kg处理的动物，卵巢 通过对黄体的观察来判断周期性 观察两组卵巢情况。 血液循环指数 离子、肝功能和血细胞成分显示没有 长期治疗效果显着。 一般毒理学 主要器官和组织的评估，无论是总体还是 微观水平，没有发现任何与治疗相关的变化。 因此，长期服用低剂量抗孕激素可预防 非人类灵长类动物怀孕，同时允许卵巢周期性和 月经规律的发生率很高。 未来的研究已计划 确定避孕作用的部位和机制 低剂量抗孕激素，例如在子宫内预防配子 运输或植入。 此外，实验将检验是否 ZK 137 316 的抗生育作用是可逆的。 如果是的话，这 可以寻求新的抗孕激素治疗方案作为潜在的治疗方法 女性避孕药。 相关出版物 Zelinski-Wooten MB, Slayden OD、Chwalisz K、Hess DL、Brenner RM、Stouffer RL。 慢性的 用低剂量的抗孕激素治疗雌性恒河猴 ZK 137 316 建立允许正常月经的养生法 周期性。 嗯，Reprod，正在出版。 斯莱登 OD、泽林斯基-伍滕 MB、 Chwalisz K、Stouffer RL、Brenner RM。 骑自行车的慢性治疗 使用低剂量抗孕激素 ZK 137 316 的恒河猴 子宫和输卵管的形态测量评估。 嗡嗡声Reprod，在 按。