HCG EXPRESSION IN PREGNANCY AND PREGNANCY LOSS

描述：我们的目标是准确地衡量率，并了解 早期妊娠丢失（EPL）和反复自然流产的原因。 这些不孕问题，特别是EPL，在某些情况下， 与环境中的生殖毒素有关。的 我们前面的假设是hCG的切口形式， 生物活性降低，在许多现有的 hCG测定，可能是由于减少了 生物活性我们的合作者和我们发现hCG EPL受试者的生物活性确实降低了。我们有 确定这种减少的原因不是存在增加 丢失受试者的hCG缺口。在这个实验中要检验的假设 建议是，怀孕成功的受试者产生早期的 具有增强的生物活性的hCG的妊娠同种型。这个hCG 同种型在注定流产的妊娠中低或不存在。我们有 开发的测定法（基于单克隆抗体B152）可以测量 早孕期hCG的同种型这种异构体存在于较高的 浓度在早期成功怀孕比hCG亚型 包括尿hCG对照品。这是一 我们提出了一个令人意想不到的和挑衅性的新观察，我们建议证明我们的 假设通过以下具体目标：1。为了确定时间进程 在整个妊娠期间，尿液和血液中B152识别的亚型 并确定B152 hCG同种型的妊娠期， 被怀孕后期的hCG所取代。2.测定B152 hCG 存在于具有以下病史的女性的血液和尿液中的同种型 反复自然流产和接受胚胎植入的妇女。 早期流产率（EPL +自然流产）为32%， 在其他人群中，这一比例更高。3.到 从早孕尿液中分离B152 hCG亚型， 它们的蛋白质和碳水化合物结构。分离并比较 孕晚期hCG亚型结构与早孕关系的研究4. 描述早期的生物活性和清除率， 妊娠hCG亚型与第三代hCG纯化形式相比 孕激素和hCG标准参考制剂。

DESCRIPTION: Our goal is to accurately measure the rate and understand the causes of early pregnancy loss (EPL) and recurrent spontaneous abortion. These infertility problems, especially EPL, can in some instances, be related to exposure to reproductive toxins in the environment. The hypothesis of our preceding proposal was that nicked forms of hCG, which have reduced biological activity, and are poorly detected in many current assays for hCG, might be causal in some losses because of diminished biological activity. Our collaborators and we have discovered that the hCG and EPL subjects does display reduced biological activity. We have determined that the cause of this reduction is not the increased presence of nicked hCG in the loss subjects. The hypothesis to be tested in this proposal is that subjects whose pregnancies succeed produce an early pregnancy isoform of hCG with enhanced biological activity. This hCG isoform is low or absent in pregnancies destined to be lost. We have developed assays (based upon monoclonal antibody B152) which can measure this early pregnancy isoform of hCG. This isoform is present in higher concentrations in early successful pregnancies than the hCG isoform comprising the reference preparations of urinary hCG. This is an unexpected and provocative new observation and we propose to prove our hypothesis by the following specific aims: 1. To determine the time course throughout pregnancy of the isoforms recognized by B152 in urine and blood and to determine the gestational period over which the B152 hCG isoform is replaced by the hCG of later pregnancy. 2. To determine the B152 hCG isoforms present in the blood and urine of women who have a history of recurrent spontaneous abortion and women undergoing embryo implantation. Early loss rate (EPL + spontaneous abortion) is 32% in a normal population and significantly higher in these other populations. 3. To isolate the B152 hCG isoforms from early pregnancy urine and determine their protein and carbohydrate structures. To isolate and compare the structure of third trimester hCG isoforms with hose of early pregnancy. 4. To characterize the biological activities and clearance rates of early pregnancy hCG isoforms as compared to hCG purified form the third trimester and hCG standard reference preparations.