Smith S K, Charnock-Jones D S, Sharkey A M
Department of Obstetrics and Gynaecology, University of Cambridge, Rosie Maternity Hospital, UK.
Hum Reprod. 1998 Jun;13 Suppl 3:237-43; discussion 244-6. doi: 10.1093/humrep/13.suppl_3.237.
There is now strong evidence that many of the actions of steroids in controlling reproduction are mediated by locally acting factors such as growth factors and cytokines. These have been shown to act both in an autocrine and paracrine manner to regulate preimplantation embryo development and migration which is necessary for placental development. The creation of mouse strains lacking genes for receptors or growth factors has proved important in defining which of these are essential in reproduction in this species and those that play a lesser role. Using this approach, a lack of leukemia inhibitory factor (LIF) in the murine endometrium has been shown to result in failed implantation. Evidence from infertile women supports the notion that abnormal expression of LIF, or the related cytokine interleukin-6 (IL-6) in the endometrium may underlie some forms of human infertility. This offers the opportunity for therapeutic intervention, if levels of these cytokines can be altered in a specific and controlled way. The recently described method of delivery of genes to the uterine epithelium provides a powerful new approach by which this could be achieved. The ability to regulate the function of specific genes in the endometrium by direct gene transfer raises the prospect of novel opportunities for therapeutic intervention.
现在有强有力的证据表明，类固醇在控制生殖方面的许多作用是由局部作用因子如生长因子和细胞因子介导的。这些因子已被证明以自分泌和旁分泌方式发挥作用，以调节着床前胚胎发育和迁移，而这对胎盘发育是必要的。事实证明，创建缺乏受体或生长因子基因的小鼠品系对于确定其中哪些对该物种的生殖至关重要以及哪些作用较小非常重要。使用这种方法，已表明小鼠子宫内膜中缺乏白血病抑制因子（LIF）会导致着床失败。来自不孕女性的证据支持这样一种观点，即子宫内膜中LIF或相关细胞因子白细胞介素-6（IL-6）的异常表达可能是某些形式人类不孕的原因。如果这些细胞因子的水平能够以特定且可控的方式改变，这就为治疗干预提供了机会。最近描述的将基因传递到子宫上皮的方法提供了一种强有力的新途径来实现这一点。通过直接基因转移调节子宫内膜中特定基因功能的能力为治疗干预带来了新的机会。
