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 is not clear whether STAT3 activation itself can cause induction of embryo implantation. In this study, the effects of RO8191, a potential STAT3 activator, on embryo implantation were investigated through a series of studies with different mouse models. We found that RO8191 can induce embryo implantation by activating the STAT3 pathway in delayed implantation mice. Furthermore, RO8191 can initiate decidualization, which is essential for embryo implantation, even in uterine epithelial-specific Stat3, Gp130, or Lifr conditional knockout (cKO) mice that exihbits infertility due to embryo implantation failure. Histomorphological observations revealed successful embryo implantation and embryonic development in Lifr cKO mice. Increased epithelial detachment and vascularization were observed in Stat3 cKO mice, and excessive inflammatory response and embryo death were observed in Gp130cKO mice. These results suggest that STAT3, Gp130 and LIFR each play a distinct role in embryo implantation and development. Although the specific mechanisms of RO8191 are not fully understood, this study providedinsights to support the application of RO8191 in treating recurent implantation failure.