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，持续服用低剂量 抗孕激素ZK 137 316(先灵公司)对成年雌性恒河猴的影响 猴子允许卵巢/月经周期，但会扰乱生长 子宫内膜的分化。以确定这些是否 生殖道的(或其他)变化足以防止 生育力(宫内妊娠)，雌性猕猴(n=10/组) 每天给予赋形剂(对照组)，0.01或0.03 mg ZK 137 316/kg 连续同居5个月前和期间的体重 已证实有生育能力的男性。交配行为是通过视觉确认的 观察，并通过检测精子判断是否发生射精 在阴道里。累计妊娠率为90%(9/10)。 在对照组中观察到。在注射0.01毫克/公斤的动物中，40%(4%) 10)怀孕，所有的怀孕都发生在 配对。0.03 mg/kg剂量组未发生妊娠(0/10) 一群人。尽管及时的月经周期发生得更频繁 在0.01 mg/kg比0.03 mg/kg处理的动物中，卵巢 从卵巢黄体的观察判断其周期性 两组均观察到卵巢。血液循环指标 离子、肝功能和血细胞成分显示 慢性治疗效果显著。普通毒理学 对主要器官和组织的评价，无论是总体评价还是 显微镜下，未发现任何与治疗相关的变化。 因此，长期服用低剂量的抗孕激素可以防止 在非人类灵长类动物中怀孕，同时允许卵巢周期和 月经规律发生率高。未来的研究正在计划中 确定避孕药的避孕作用部位(S)和作用机理(S) 低剂量的抗孕激素，例如在子宫内，以防止配子 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。如果是这样的话，这个 抗孕激素的新疗法可以作为一种潜在的治疗方法 女性避孕药。相关出版物泽林斯基-伍腾MB， Slayden OD，Chwalisz K，Hess DL，Brenner RM，Stouffer RL。慢性 小剂量抗孕激素对雌性恒河猴的治疗作用 ZK 137 316建立允许月经正常的养生法 周期性。Hum Reprod，在媒体上。Slayden OD，Zelinski-Wooten MB Chwalisz K，Stouffer RL，Brenner RM.自行车运动的慢性治疗 恒河猴服用低剂量抗孕激素ZK 137 316 子宫和输卵管的形态测量评估。Hum Reprod，In 按下。