NAD+: Placental nicotinamide adenine dinucleotide modulates the timing of labor.

Labor is mediated proximately by prostaglandin signaling within gestational tissues and must be tightly regulated for birth to occur after appropriate fetal development. Metabolic changes accompanying gestational aging have been postulated as a determinant of birth timing, but specific nutrients, sensors, and messengers remain obscure. We report that placental nicotinamide adenine dinucleotide (NAD + ) dynamically tunes gestational length. Depletion of placental NAD + in mice provoked labor onset, mediated by the role of NAD + as a cofactor for 15-hydroxy prostaglandin dehydrogenase, an enzyme responsible for suppressing prostaglandin accumulation. Augmentation of placental NAD + prolonged gestation at baseline and in a model of preterm labor. These findings suggest a central role for metabolic exhaustion in provoking labor and reveal potential therapeutic avenues for preterm labor and the optimization of labor induction.