A proposed model of a clock that governs the length of human pregnancy.

In brief: The mechanisms that determine the length of pregnancy remain undetermined. Here, we review what has been previously published on the topic and incorporate new data to describe a molecular model in which placental stress and fetal signaling ultimately lead to labor onset in uncomplicated pregnancies.

Abstract: The mechanisms that govern the length of human pregnancy have not been determined, while preterm birth remains the leading cause of death and disability in newborns worldwide. Here, we review recent data to generate a novel hypothesis about how the pregnancy clock may function to initiate human labor in uncomplicated pregnancies. In this model, placental stress induced by the growing fetus drives placental production of NFKB, which is then activated by exosomes containing platelet-activating factor and complement 4-binding protein-A from the mature fetus, to drive pro-labor genes in the placenta. A better understanding of the clock that triggers labor may lead to new, more effective therapies to prevent spontaneous preterm birth.