The blastocoel of mammalian embryos is a fluid-filled cavity surrounded by a monolayer of trophectoderm, and its formation marks one of the earliest stages of embryonic development. During this process, the trophectoderm undergoes a metabolic shift toward oxidative phosphorylation, which increases the level of reactive oxygen species (ROS) and places the blastocyst under oxidative stress. In this issue (), Melvin DePamphilis and Kotaro Kaneko uncover a role for TEAD4, which was previously thought to specify trophectoderm, in managing oxidative stress and establishing energy homeostasis during murine blastocoel formation. The authors show that under conditions that mimic the in vivo environment, TEAD4 is necessary for trophectoderm and blastocoel formation, but that this requirement is lost when conditions are manipulated to minimise oxidative stress. The authors demonstrate that Tead4-/- mitochondria have a reduced membrane potential in trophoblast giant cells, and furthermore that TEAD4 could localise to mitochondria, possibly to prevent accumulation of ROS. These data reveal a metabolic requirement for TEAD4 in the developing mouse embryo, rather than in trophectoderm lineage specification.
