ENDOCRINE BIOMARKERS OF EARLY FETAL LOSS IN MACAQUES FOLLOWING EXPOSURE TO TCDD

接触 TCDD 后猕猴早期流产的内分泌生物标志物

• 批准号: 6116648
• 负责人: ANDREW G HENDRICKX
• 金额: $ 5.91万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2000-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6116648
• 关键词: Mammalia; clinical research; endocrine gland /system; infant mortality; low birth weight infant human; mother /infant health care; reproductive system; women's health

beneath the table to the abstract. Use the Word Count cmd under Utilites menu for counting Significance Little information is available on embryo-maternal signaling during early pregnancy in primates. An increased understanding of the endocrine events that characterize this period in the nonhuman primate model will enhance our ability to monitor spontaneous and toxicant-induced pregnancy loss in humans. Objectives To study the endocrinology of early pregnancy loss induced by TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) in the cynomolgus monkey. The macaque exhibits similar endocrine and morphological characteristics during early pregnancy as described in humans and is sensitive to TCDD toxicity. Results Single doses of TCDD (1, 2, and 4 mg/kg) administered during early pregnancy resulted in fetal loss in the majority of animals (10/12). The primary endocrine alterations associated with fetal loss were decreases in serum estradiol and bioactive chorionic gonadotropin (CG) concentrations. Less pronounced decreases in serum progesterone, and relaxin were observed; there was no effect on immunoreactive CG. These results indicate that TCDD targets specific components of the CG synthetic machinery within the trophoblast to alter the functional capacity of the hormone. Moreover, these endocrine alterations occurred prior to overt signs of reproductive toxicity (i.e., early fetal loss). The relatively long interval from TCDD exposure to fetal loss (10-20 days) suggests that TCDD may have a direct toxic effect on the embryo. Future Directions Use of bioactive:immunoreactive CG ratio to monitor pregnancy outcome in human populations. KEY WORDS abortion, pregnancy, chorionic gonadotropin, estrogen, progesterone FUNDING NIH Grants ES06198 and RR00169

桌子下面的抽象。 使用Word Count cmd 利用菜单计算重要性信息很少 在妊娠早期， 灵长类动物 增加对内分泌事件的了解， 在非人类灵长类动物模型中描述这一时期将增强 我们监测自发性和毒物性流产的能力 在人类身上。 目的探讨早期妊娠的内分泌学 TCDD（2，3，7，8-四氯二苯并-对-二恶英）在 猕猴。 猕猴表现出类似的内分泌和 在早期妊娠期间的形态特征，如 对TCDD毒性敏感。 结果单剂量 妊娠早期给予TCDD（1、2和4 mg/kg）， 在大多数动物中胎仔丢失（10/12）。 主 与胎儿丢失相关的内分泌改变减少， 血清雌二醇和生物活性绒毛膜促性腺激素 浓度的 血清孕酮下降不太明显， 松弛素的观察;免疫反应CG没有影响。 这些结果表明，TCDD的目标是CG的特定组件 滋养层内的合成机制改变功能 荷尔蒙的能力。 此外，这些内分泌变化 发生在明显的生殖毒性迹象之前（即，早期 胎儿丢失）。 TCDD暴露至胎儿的相对较长时间间隔 损失（10-20天）表明，TCDD可能对 胚胎。 生物活性物质的使用：免疫反应性CG 以监测人群中的妊娠结局。 关键词 流产，妊娠，绒毛膜促性腺激素，雌激素，孕酮 资助NIH赠款ES 06198和RR 00169