HCG EXPRESSION IN PREGNANCY AND PREGNANCY LOSS

描述：我们的目标是准确测量比率并了解 早孕丢失(EPL)和反复自然流产的原因。 这些不孕不育问题，特别是早泄，在某些情况下可能是 与暴露在环境中的生殖毒素有关。这个 我们之前提议的假设是hCG的缺口形式，它 生物活性降低，且在许多当前情况下检测不到 HCG的检测，可能是某些损失的原因，因为减少了 生物活性。我们的合作者和我们发现hCG 而EPL受试者确实表现出生物活性降低。我们有 确定减少的原因不是增加的存在 在丢失的受试者中的hCG。这里要检验的假设是 建议怀孕成功的受试者早产 人绒毛膜促性腺激素的妊娠亚型具有增强的生物活性。这个hCG 在注定要失去的妊娠中，亚型是低的或不存在的。我们有 开发的分析方法(基于单抗B152)可以测量 人绒毛膜促性腺激素的这种早孕亚型。这种异构体在高等生物中存在 人绒毛膜促性腺激素亚型在早期妊娠中的浓度 包括尿液hCG参比制剂。这是一个 意想不到的和挑衅性的新发现，我们建议证明我们的 假设的具体目的如下：1.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亚型的妊娠期 取而代之的是妊娠后期的hCG。2.测定B152 hCG 有血液病病史的女性血液和尿液中存在异构体 反复自然流产和接受胚胎植入的妇女。 正常的早期失败率(EPL+自然流产)为32% 而在这些其他人口中，这一比例要高得多。3.至 从妊娠早期尿液中分离B152人绒毛膜促性腺激素亚型 它们的蛋白质和碳水化合物结构。来分离和比较 妊娠晚期人绒毛膜促性腺激素异构体的结构。4. 以表征早期的生物活性和清除率 妊娠人绒毛膜促性腺激素亚型与第三代纯化hCG的比较 三孕期和人绒毛膜促性腺激素标准参考制剂。

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.