Peri-Conceptional Biomonitoring

描述（由申请人提供）：该提案将解决1）人类发育早期阶段环境暴露的准确评估，以及2）这些暴露与精液质量和300对试图怀孕夫妇的社区居住队列中怀孕时间的关联。选择用于测量的污染物，消毒副产物（DBP）和双酚A（BPA），在动物模型和有限的流行病学研究中与不良生殖结果相关。这些和其他环境污染物的暴露没有通过传统的流行病学手段进行很好的测量，例如使用问卷调查的参与者回忆或怀孕早期的环境监测，例如在第一次产前检查时，或生态措施，例如分配饮用水系统监测报告的污染物水平。生物标志物可以更精确地估计体内剂量，但对于短暂照射和半衰期短的化学品，必须在正确的时间收集生物样本，以便根据关键的发育窗口对个人照射进行适当分类。如果接触是短暂的，或者如果相关化学品的半衰期很短，在怀孕早期收集的生物标志物可能太晚而无法检测围概念接触。在这种设计中，影响受孕概率的排卵期暴露也会被遗漏，因为未能怀孕的夫妇将不会进入产前护理。具体目标1.在人类孕前队列中进行前瞻性的、排卵期的消毒副产物（DBP）和双酚A（BPA）生物监测，使用一种新的策略，即通过观察社区居民的生育迹象触发环境和生物标本的自我收集。2.评价男性和女性的前瞻性测量暴露量与精液质量和妊娠时间的生殖结局之间的相关性。3.与前瞻性排卵期生物监测和采样相比，量化常用的回顾性暴露评估方法（参与者使用回忆问卷和/或存档环境监测数据自我报告既往暴露）产生的错误分类偏倚程度。建议招募一个受孕前队列，通过生物标志物和问卷进行前瞻性暴露评估，评价暴露与妊娠时间的相关性，并将前瞻性测量的暴露与回顾性估计的暴露进行比较。收集的生物标本将作为储存库，供未来分析使用。该队列和标本库的创建将启动主要研究者（早期）Porucznik的独立职业生涯。

DESCRIPTION (provided by applicant): This proposal will address 1) accurate assessment of environmental exposures during the earliest phases of human development, and 2) association of these exposures with semen quality and time to pregnancy in a community-dwelling cohort of 300 couples trying to conceive. The contaminants selected for measurement, disinfection by-products (DBP) and bisphenol-A (BPA), have been associated with adverse reproductive outcomes in animal models and in limited epidemiologic studies. Exposure to these and other environmental contaminants is not well measured via traditional epidemiologic means such as participant recall using questionnaires or environmental monitoring in early pregnancy, such as at the time of the first prenatal visit, or ecologic measures such as assignment of contaminant levels reported from drinking water system monitoring. Biomarkers can allow for more precise estimates of internal dose, but for transient exposures and chemicals with short half-lives, the biological specimen must be collected at the right time in order to properly classify individual exposure in relation to critical developmental windows. Biomarkers collected in early pregnancy may be too late to detect peri-conceptional exposure if the exposure was transient or if the relevant chemical had a short half-life. Peri-ovulational exposures that affect probability of conception would also be missed in this type of design, as couples who fail to conceive will not enter into prenatal care. SPECIFIC AIMS 1. Conduct prospective, peri-ovulational biomonitoring for disinfection by-products (DBP) and bis-phenol-A (BPA) in a human preconception cohort using a novel strategy of self-collection of environmental and biological specimens triggered by observation of fertility signs in a community-dwelling population. 2. Evaluate the association between prospectively measured exposures in the male and the female and the reproductive outcomes of semen quality and time to pregnancy. 3. Quantify the degree of misclassification bias generated by retrospective exposure assessment methods in common use (participant self-report of past exposure using a recall questionnaire and/or archival environmental monitoring data) compared to prospective peri-ovulational biomonitoring and sampling. The proposal is to recruit a pre-conception cohort, conduct prospective exposure assessment via biomarkers and questionnaires, evaluate the association of exposure with time to pregnancy, and compare prospectively measured exposures with retrospectively estimated exposures. Collected biospecimens will be banked as a repository for future analyses. Creation of this cohort and specimen bank will launch the independent career of Principal Investigator (Early Stage) Porucznik.