BIOMARKERS FOR HUMAN REPRODUCTIVE EPIDEMIOLOGY

该项目将利用以前在中国进行的三项关于生殖健康的大型前瞻性研究中收集的暴露数据和样本。我们的目标是调查在月经周期的特定阶段环境引起的扰动的不良影响。主要结果包括卵泡延长、雌激素分泌减少、骨丢失增加和生育能力下降。该研究将使用来自1,200名妇女的所有合格周期进行轮班工作研究，以证明以下内容：黄体晚期尿FSH代谢物的变化可以预测随后周期的长卵泡期;长卵泡期与雌酮结合物的每日排泄量较低相关。在周期的前五天，整个卵泡期尿骨标记物的排泄量较高，与正常长度的卵泡期相比，受孕率较低;前一个黄体期的轮班变化与卵泡期长、雌激素排泄量低、骨吸收增加和生育力低有关。将分析来自石化研究中的600名妇女和铅研究中的800名妇女的额外样本，并结合来自轮班工作研究的受试者，以证明以下内容：在未暴露的受试者中，与hCG B：I比率不变的妊娠失败相比，在妊娠检测后一周内，将在存活妊娠中观察到尿hCG B：I比率的显著增加;在妊娠失败的妇女中，与未暴露的妇女相比，暴露于环境危害的妇女在妊娠检测后的一周内更可能经历B：I比率的显著增加，并且与存活的大样本来源相比，在妊娠终止前的几天内，hCG B：I比率将显著下降;（2）几个最近开发的生物标志物将被应用于阐明不良生殖结果所涉及的生物学机制;（3）轮班工作是一种客观的测量方法，应该没有测量误差，将被用来测试我们提出的几个假设;（4）前瞻性研究设计可以消除可能混淆回顾性研究的缺陷或潜在偏倚;（5）本研究可以作为研究其他生殖风险的生物学机制的范例。

This project will utilize exposure data and samples previously collected in three large prospective studies on reproductive health in China. Our objective is to investigate the adverse effects of environmentally-induced perturbations during specific stages of the menstrual cycle. The major outcomes of interest include prolonged follicular, decreased estrogen secretion, increased bone loss and decreased fecundability. The study will use all eligible cycles from 1,200 women in a rotating shift work study to demonstrate the following: changes in urinary FSH metabolites in the late luteal phase can predict a long follicular phase in the subsequent cycle; a long follicular phase is associated with lower daily excretion of estrone conjugates. In the first five days of the cycle, higher excretion of urinary bone markers throughout the follicular phase and lower conception rates compared to a normal length follicular phase; work shift changes in the preceding luteal phase are associated with a long follicular phase, low estrogen excretion, increased bone resorption and low fecundability. Additional samples from 600 women in petrochemical study and 800 women in lead study combined with the subjects from the rotating shift work study will be analyzed to demonstrate the following: among non- exposed subjects a significant increase in the urinary hCG B:I ration during the week following pregnancy detection will be observed in surviving pregnancies compared to failing pregnancies in which the hCG B:I ratio will not change; and of the women with failing pregnancies, those exposed to an environmental hazard are more likely to experience a significant increase in the B:I ratio during the week following pregnancy detection than are the unexposed, and there will be a significant decline in the hCG B:I ratio over a period of several days prior to termination of the pregnancy compared with surviving large sample source; (2) several recently developed biomarkers will be applied to elucidate the biological mechanisms involved in adverse reproductive outcomes; (3) shift work, which is an objective measurement and should be free of measurement error, will be used to test several of our proposed hypotheses; (4) the prospective study design can eliminate flaws or potential biases that can confound retrospective studies; and (5) this study can serve as a paradigm to study the biological mechanisms of other reproductive risk.