MI PBB Cohort 30 years later: Endocrine Disruption?

MI PBB 队列 30 年后：内分泌干扰？

• 批准号: 6929959
• 负责人: MICHELE MARCUS
• 金额: $ 55.94万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6929959
• 关键词: bioaccumulation; biphenyl compounds; bromine; children; clinical research; embryo /fetus toxicology; endocrine disorder; endocrine gland /system; epidemiology; fertility; food chain contamination; gender difference; human puberty; human subject; longitudinal human study; menstrual cycle; ovary; personal log /diary; questionnaires; reproduction; reproductive development; spontaneous abortion; toxicology; urinalysis

DESCRIPTION (provided by applicant): The investigators propose a targeted investigation of endocrine-related outcomes in individuals in the Michigan PBB Registry and their offspring to follow up intriguing findings of a study recently completed by this team. In 1973, inadvertent substitution of a livestock feed supplement with fire retardant led to widespread contamination of meat and dairy products in Michigan with polybrominated biphenyls (PBBs), a class of chemicals toxicologically similar to PCBs, PBDE, DDE and other halogenated organics suspected to disrupt endocrine function. Over 4000 individuals with high likelihood of exposure were subsequently enrolled into the Michigan PBB Registry, and serum samples were analyzed for PBB. The proposers recently completed a twenty-year follow up survey of women in the registry regarding occurrence of endocrine-related outcomes, and the current application will pursue key findings of this survey as follows. The observation of an association of perinatal PBB exposure with reduced age at menarche in the daughters of registry participants will be followed up in two ways: 1) an expanded assessment of ovarian function in a subgroup of the daughters, using menstrual diaries and hormonal assays of daily urine samples (50 high exposure, 50 low exposure), and 2) an investigation of pubertal development in the sons of women in the registry to assess whether analogous impacts on pubertal development are observed in the boys, using a questionnaire assessment of Tanner stages and other pubertal landmarks in sons less than 18 years of age (n=204). The suggestion of an excessive spontaneous abortion rate among the exposed daughters of reproductive age will be followed up by: 1) updating the reproductive histories of the daughters over age 18 (n=214), and 2) by determining reproductive success in the sons over 18 years of age (n=218). Finally, the finding of altered menstrual cycle characteristics among the women in the registry will, be pursued by performing a menstrual diary and urinary hormone study in the adult women (50 high exposure, 50 low exposure) similar to that proposed for the daughters. Each of the proposed investigations allows targeted, efficient follow up of the important findings observed in the previous study, and will provide further insight into possible impacts of this class of chemicals on pubertal development, reproductive health and ovarian function.

描述（由申请人提供）：研究人员提议对密歇根 PBB 登记处的个体及其后代的内分泌相关结果进行有针对性的调查，以跟进该团队最近完成的一项研究的有趣发现。 1973 年，无意中用阻燃剂替代了牲畜饲料补充剂，导致密歇根州的肉类和乳制品广泛受到多溴联苯 (PBB) 污染，这种化学物质的毒理学与 PCB、PBDE、DDE 和其他疑似扰乱内分泌功能的卤化有机物类似。随后，超过 4000 名高接触可能性的个体被登记到密歇根州 PBB 登记处，并对血清样本进行了 PBB 分析。提案者最近完成了一项针对登记册中的女性有关内分泌相关结果发生情况的二十年跟踪调查，当前的申请将追究该调查的主要结果如下。将通过两种方式对登记参与者的女儿围产期 PBB 暴露与初潮年龄降低之间的关系进行跟踪：1) 使用月经日记和每日尿液样本的激素测定（50 个高暴露，50 个低暴露）对女儿亚组的卵巢功能进行扩大评估，以及 2) 对妇女儿子的青春期发育进行调查 登记处使用对 18 岁以下儿子 (n=204) 的坦纳阶段和其他青春期标志的问卷评估来评估是否在男孩中观察到对青春期发育的类似影响。对于暴露的育龄女儿自然流产率过高的建议，将采取以下措施：1) 更新 18 岁以上女儿 (n=214) 的生育历史，2) 通过确定 18 岁以上儿子 (n=218) 的生育成功率。最后，将通过对成年女性（50 名高暴露，50 名低暴露）进行月经日记和泌尿激素研究来发现登记中女性月经周期特征改变的结果，类似于针对女儿提出的研究。每项拟议的研究都可以对先前研究中观察到的重要发现进行有针对性的、有效的跟踪，并将进一步深入了解此类化学物质对青春期发育、生殖健康和卵巢功能可能产生的影响。