BIOMARKERS FOR HUMAN REPRODUCTIVE EPIDEMIOLOGY

本项目将利用之前在中国生殖健康的三个大型前瞻性研究中收集的暴露数据和样本。我们的目的是研究在月经周期的特定阶段环境引起的扰动的不利影响。主要结果包括卵泡延长，雌激素分泌减少，骨质流失增加和生育能力下降。该研究将使用来自1200名轮换轮班工作的女性的所有符合条件的周期来证明以下内容：黄体晚期尿卵泡刺激素代谢物的变化可以预测随后周期中较长的卵泡期；卵泡期较长与雌二醇偶联物的日排泄量较低有关。在月经周期的前5天，与正常长度的卵泡期相比，整个卵泡期尿骨标志物的排泄量较高，受孕率较低；黄体期前的轮班变化与卵泡期长、雌激素分泌低、骨吸收增加和生育能力低有关。来自石化研究中的600名妇女和铅研究中的800名妇女以及轮班工作研究中的受试者的额外样本将进行分析，以证明以下情况：在未暴露的受试者中，在妊娠检测后的一周内，将观察到存活妊娠的受试者与失败妊娠的受试者相比，hCG B:I比例显着增加。在怀孕失败的妇女中，暴露于环境危害的妇女比未暴露的妇女更有可能在怀孕检测后一周内显着增加B:I比率，并且与幸存的大样本来源相比，在终止妊娠前几天内hCG B:I比率将显着下降；(2)最近开发的几种生物标志物将用于阐明不良生殖结局的生物学机制；(3)轮班工作，这是一个客观的测量，应该没有测量误差，将用于检验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差；(5)本研究可为研究其他生殖风险的生物学机制提供范例。

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.