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多溴联苯登记处的个人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，由于疏忽将牲畜饲料添加剂替换为阻燃剂，导致密歇根州的肉类和乳制品受到多溴联苯（PBBs）的广泛污染，PBBs是一类化学品，在毒理学上类似于PCB，PBDE，DDE和其他卤化有机物，被怀疑会破坏内分泌功能。随后，密歇根州多溴联苯登记处登记了4，000多名极有可能接触多溴联苯的人，并对血清样本进行了多溴联苯分析。提议者最近完成了一项关于内分泌相关结局发生率的登记研究中女性的20年随访调查，当前申请将追求该调查的关键结果，如下所示。将以两种方式跟踪观察围产期接触多溴联苯与登记参与者女儿初潮年龄降低之间的关系：1）使用月经日记和每日尿样的激素测定，对女儿的一个亚组进行卵巢功能的扩展评估（50例高暴露，50例低暴露），以及2）对登记册中女性的儿子进行青春期发育调查，以评估是否在男孩中观察到对青春期发育的类似影响，使用问卷评估坦纳阶段和其他青春期标志的儿子小于18岁（n=204）。对于暴露的育龄女儿中自发性流产率过高的建议，将采取以下措施：1）更新18岁以上女儿的生殖史（n=214），2）确定18岁以上儿子的生殖成功率（n=218）。最后，将通过在成年女性中进行月经日记和尿激素研究（50例高暴露，50例低暴露）来追踪登记研究中女性月经周期特征改变的结果，该研究与为女儿拟定的研究相似。每一项拟议的调查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跟踪，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。