PPAR gamma is required for placental, cardiac, and adipose tissue development

The nuclear hormone receptor PPAR gamma promotes adipogenesis and macrophag e differentiation and is a primary pharmacological target in the treatment of type II diabetes. Here, we show that PPAR gamma gene knockout results in two independent lethal phases. Initially, PPAR gamma deficiency interferes with terminal differentiation of the trophoblast and placental vasculariza tion, leading to severe myocardial thinning and death by E10.0. Supplementi ng PPAR gamma null embryos with wild-type placentas via aggregation with te traploid embryos corrects the cardiac defect, implicating a previously unre cognized dependence of the developing heart on a functional placenta. A tet raploid-rescued mutant surviving to term exhibited another lethal combinati on of pathologies, including lipodystrophy and multiple hemorrhages. These findings both confirm and expand the current known spectrum of physiologica l functions regulated by PPAR gamma.