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)：研究人员建议对密歇根州PBB注册处的个人及其后代进行一项与内分泌相关的结果有针对性的调查，以跟进该团队最近完成的一项有趣的研究结果。1973年，在密歇根州，由于不小心将一种牲畜饲料添加剂替代为阻燃剂，导致肉类和乳制品被多溴联苯(PBBS)广泛污染，多溴联苯(PBBS)是一类毒理上类似于多氯联苯、多溴联苯醚、DDE和其他疑似扰乱内分泌功能的卤代有机物。超过4000名高暴露可能性的人随后被登记到密歇根州PBB登记处，并对血清样本进行了PBB分析。提倡者最近完成了一项关于内分泌相关结果发生情况的对登记的妇女进行的为期20年的跟踪调查，目前的申请将继续这项调查的主要结果如下。将通过两种方法观察登记参与者的女儿围产期多溴联苯暴露与月经初潮年龄降低之间的关系：1)利用月经日记和每日尿样荷尔蒙分析(高暴露50例，低暴露50例)，扩大对一组女儿的卵巢功能的评估；2)调查登记妇女的儿子的青春期发育，以评估是否对男孩的青春期发育也有类似的影响，方法是对18岁以下儿子的Tanner阶段和其他青春期标志进行问卷评估(n=204)。对暴露在生育年龄的女儿中自然流产率过高的建议将采取以下后续行动：1)更新18岁以上女儿的生育史(n=214)，以及2)确定18岁以上儿子的生育成功率(n=218)。最后，将通过对成年妇女(50人高暴露，50人低暴露)进行月经日记和尿液激素研究来发现登记的妇女中月经周期特征发生变化，类似于为女儿建议的研究。每一项拟议的调查都可以有针对性地、有效地跟进前一项研究中观察到的重要发现，并将进一步深入了解这类化学品对青春期发育、生殖健康和卵巢功能的可能影响。