Hippo signaling in mammalian reproduction

The Hippo signaling pathway, so named for its massive overgrowth mutant phenotypes, has become one of the most exciting signaling pathways to emerge in the field of reproductive biology. While disruption of Hippo is associated with tumorigenesis in many organs and tissues, relatively less is understood about the normal roles of Hippo signaling in the reproductive organs. Here, we highlight the recent literature illuminating the roles of Hippo pathway members in mouse and human reproduction. We place special emphasis on the inputs and outputs of Hippo signaling during preimplantation development, where Hippo signaling has been extensively studied in both mouse and human. We note a common emerging theme is the critical and highly conserved role of Hippo signaling in epithelia of the reproductive organs. We also discuss human reproductive disorders, whose etiology may be related to dysregulation of Hippo signaling, and possible therapies that have been proposed to correct this dysregulation. Finally, we describe the edge of our knowledge, which currently limits our understanding of Hippo signaling in reproductive health and disease.