Uterine sensing of the embryo.

Abstract

The uterus uses the Wnt pathway to sense the embryo during initial implantation. In the Hans Christian Andersen tale, a young princess is identified by her ability to sense a pea buried deep within a thick layer of mattresses. In this issue of PNAS, Mohamed et al. (1) provide new insight into the molecular mechanism of embryo implantation by identifying the Wnt pathway as part of the system the uterus uses to sense and respond to the relatively tiny embryo during the initial stage of implantation in mice. Ovarian steroids coordinate embryonic development to an attachment-competent state with maturation of the uterus to a receptive state. The latter is a transient process that is followed by a refractory period requiring reinitiation of the uterine cycle before again becoming receptive. A small rise in estrogen levels, i.e., nidatory estrogen, is required to trigger the implantation process, including expression of the molecules mentioned above in rodents. It has long been recognized that local events occur in the uterus in response to the implanting embryo, and a number of early molecular markers of these events have been described (2). Mohamed et al. (1) used a mouse model in which a lacZ reporter gene is activated by T cell factor/lymphoidenhancer factor, indicating that nuclear β-catenin signaling, a downstream event in canonical Wnt pathway activation, has occurred. Their studies demonstrate not only that this pathway is activated locally in response to the implanting embryo but also that embryo-derived Wnts mediate the process. Wnt7a, but not Wnt5a, appears to be particularly effective in triggering implantation-related responses. Consistent with this observation, previous studies by Mohamed et al. (3) demonstrated that mouse embryos increase expression of Wnt7a mRNA during development from the morula to the blastocyst stage. Furthermore, they show that the Wnt antagonist, secreted frizzled related …