Epithelial-trophoblast interactions in human embryo implantation: role for interleukin 11 and leukemia inhibitory factor

不孕不育、自然流产和先兆子痫是主要的临床问题。女性不孕不育通常是由于植入失败，许多试管受精胚胎无法植入。胎盘的适当发育对妊娠结局至关重要，胎盘放置不当会导致自然流产。然而，如果继续妊娠时胎盘发育不良，母亲很可能会发展为先兆子痫，随后对母亲和婴儿都会产生严重的不良后果。胎盘闭锁是导致低出生体重儿和产妇死亡的最常见原因。低出生体重通常是妊娠合并先兆子痫的结果，与以后的生活障碍(包括高血压、糖尿病、冠心病和肥胖症)有关。白介素11和白血病抑制因子是已知的极少数对小鼠胚胎植入至关重要的分子。它们在人类不孕症中的作用尚不清楚，尽管有证据表明LIF降低与女性植入失败有关。这些分子在灵长类动物子宫和胎盘中的分布表明，它们在准备植入子宫衬里和女性胎盘发育过程中发挥着重要作用。该项目将研究植入部位局部产生的IL-11和LIF如何影响人类子宫和胎盘的形成。目前还没有诊断女性子宫内膜不孕症的方法，也没有确定胎盘是否发育充分的方法。这些研究将提供有关这两个分子的作用及其作为治疗不孕症和与妊娠相关的重大疾病的急需诊断和治疗工具的靶标的新的关键信息。应用这种新的检测方法将对母亲和孩子的健康产生终生的好处。

Infertility, spontaneous abortion and pre-eclampsia are major clinical problems. Female infertility is frequently due to implantation failure and many IVF embryos fail to implant. Appropriate development of the placenta is critical to the outcome of pregnancy and inadequate placentation can result in spontaneous abortion. However, if the pregnancy continues with a poorly developed placenta, the mother is likely to develop pre-eclampsia with subsequent major adverse outcomes for both mother and baby. Pre-clampsia is the most common cause of low birth weight infants and also of maternal death. Low birth weight, which is commonly an outcome of a pregnancy with pre-eclampsia, correlates with disorders later in life (including hypertension, diabetes, coronary heart disease and obesity). Interleukin (IL)-11 and leukemia inhibitory factor (LIF) are among very few molecules known to be critical for embryo implantation in the mouse. Their roles in human infertility are not well understood, although there is evidence that decreased LIF is associated with implantation failure in women. The distribution of these molecules within the uterus and placenta in primates suggests they have important roles in preparing the uterine lining for implantation and for development of a placenta in women. This project will examine how IL-11 and LIF that are locally produced at implantation sites affect the human uterus and the formation of the placenta. There is still no means of readily diagnosing endometrial infertility in women or of establishing whether the placenta is developing adequately. These studies will provide new critical information regarding the roles of these two molecules and their potential usefulness as targets for much- needed diagnostic and therapeutic tools for infertility and major diseases associated with pregnancy. Application of such new tests will produce lifelong benefits to the health of both the mother and child.