RO8191, a new compound for initiating embryo implantation in mice

Abstract

During early pregnancy in mice, leukemia inhibitory factor (LIF) regulates embryo implantation by activating the JAK/STAT3 signaling pathway. The STAT3 pathway has been recognized to play a critical role in embryo implantation; however, it remains unclear whether STAT3 activation alone is sufficient to induce implantation. In this study, we investigated the effects of RO8191, a potential STAT3 activator, on embryo implantation through a series of studies with different mouse models. We found that RO8191 can induce embryo implantation and decidual reaction by activating STAT3, but not STAT1, signaling in both epithelial and stromal compartments in delayed implantation models. Furthermore, RO8191 was able to rescue implantation and establish pregnancy even in uterine epithelial-specific Lifr conditional knockout (cKO) mice, which exhibit infertility due to implantation failure. In contrast, in uterine epithelial-specific Stat3 or Gp130 conditional knockout (cKO) mice, which also show embryo implantation failure, RO8191 induces only a partial decidual response. These results suggest that STAT3, Gp130 and LIFR each play distinct roles in embryo implantation and development. Although the detailed mechanisms underlying RO8191's action remain to be elucidated, our findings provide insights supporting its potential application in treating recurrent implantation failure.