Two Multipotential Transcription Factors, NF-kappaB and Stat-3, Play Critical and Hierarchal Roles for Implantation

Implantation, the beginning of fetal life in utero, has complex and dynamic processes including apposition and attachment of embryo to the uterine endometrial surface, invasion, placentation and decidualization. In mice, the period when uterus is available to accept the conceptus implanted called “implantation window”, is a very limited time, around day 3-5 post-coitum (p.c.). Orchestral regulation of various molecules including cytokines, growth factors, and matrixrelated molecules should play an important role in endometrium during implantation. Many reports focused on the strict physiological control of implantation within uterine endometrial epithelium and stroma. Some genetargeting studies indicated several implantation failure models. However, these experimental settings often do not reflect clinical scenario (1). In women, most of the causes of implantation failure are supposed to be reversible process, because the definitive and hereditary implantation failure may be rare and the patient may conceive at some stage of cycle. It could be suggested that it is suitable to use a local and transient gene transfer system for investigation of the implantation mechanism, because the uterus can play different roles and its functions are dependent on short term events during life. Moreover, uterus is the applicable organ for local gene therapy without any operation, because it is tubular organ accessible from vagina. To modulate the uterine function during implantation period, we first established in vivo transient gene transfer system in murine uterus.