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: 6277888
• 负责人: ANDREW G HENDRICKX
• 金额: $ 5.99万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6277888
• 关键词: Mammalia; Primates; biological products; infant mortality; low birth weight infant human; model design /development; reproductive system; technology /technique

Significance Although the endocrinology of normal pregnancy has been well characterized in humans, there is little information on the endocrine events associated with early pregnancy loss resulting from known toxic exposures. This type of information could be used to monitor the reproductive function of women exposed to environmental hazards. 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 (g/kg) administered during early pregnancy resulted in fetal loss in the majority of animals (10/12). The primary endocrine alteration associated with fetal loss was lowered steroid levels (estrogen and progesterone) indicative of a direct effect of TCDD on ovarian function. There were less notable changes in the production of chorionic gonadotropin by the trophoblast. Similarly, relaxin production by the ovary was largely unaffected. The relatively long time from TCDD exposure to embryonic death (10-20 days) is consistent with a delayed effect on the conceptus that could involve the endocrinology of the maternal-fetal unit or be the result of a direct action on the embryo. Future Directions To further characterize TCDD-induced alterations of ovarian hormone production in vitro using different ovarian cell populations. KEYWORDS TCDD, abortion, pregnancy, hormones

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