MI PBB Cohort 30 years later: Endocrine Disruption?

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，以跟踪该团队最近完成的一项有趣的研究结果。1973年，一种牲畜饲料添加剂被误用阻燃剂，导致密歇根州的肉类和奶制品普遍受到多溴联苯（PBBs）的污染。多溴联苯是一类化学物质，毒理学上与多氯联苯、多溴二苯醚、二苯二苯醚和其他被怀疑会破坏内分泌功能的卤化有机物相似。随后，超过4000名极有可能接触多氯联苯的人被登记到密歇根多氯联苯登记处，并对血清样本进行了多氯联苯分析。提议者最近完成了一项关于内分泌相关结果发生的20年随访调查，目前的申请将追求这项调查的主要发现如下。围产期多氯联苯暴露与登记参与者女儿月经初潮年龄降低的关系观察将通过两种方式进行随访：1)对女孩亚组的卵巢功能进行扩展评估，使用月经日记和每日尿液样本的激素测定（50例高暴露，50例低暴露）；2)对登记的女性的儿子的青春期发育进行调查，以评估是否在男孩身上观察到类似的影响，使用问卷调查评估Tanner阶段和18岁以下儿子的其他青春期标志（n=204）。对于暴露的育龄女儿自然流产率过高的提示，将通过以下方法进行随访：1)更新18岁以上女儿的生育史（n=214）； 2)测定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名高暴露，50名低暴露）进行月经日记和尿激素研究，以发现登记妇女月经周期特征的改变，类似于对女儿提出的研究。每一项拟议的调查都允许对先前研究中观察到的重要发现进行有针对性的、有效的后续研究，并将进一步深入了解这类化学物质对青春期发育、生殖健康和卵巢功能的可能影响。

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.