Coordinated regulation of fetal and maternal prostaglandins directs successful birth and postnatal adaptation in the mouse

Cyclooxygenase (COX)-derived prostaglandins (PGs) regulate numerous materna l-fetal interactions during pregnancy. PGs stimulate uterine contractions a nd prepare the cervix for parturition, whereas in the fetus, PGs maintain p atency of the ductus arteriosus (DA), a vascular shunt that transmits oxyge nated placental blood to the fetal systemic circulation. However, the origi n and site of action of these PGs remain undefined. To address this, we ana lyzed mice lacking COX-1 (null mutation) or COX-2 (pharmacologic inhibition ) or pups with a double null mutation. Our results show that COX-1 in the u terine epithelium is the major source of PGs during labor and that COX-1(-/ -) females experience parturition failure that is reversible by exogenous P Gs, Using embryo transfer experiments, we also show that successful deliver y occurs in COX-1(-/-) recipient mothers carrying wild-type pups, establish ing the sufficiency of fetal PCs for parturition. Although patency of the D A is PG dependent, neither COX-1 nor COX-2 expression was detected in the f etal or postnatal DA, and offspring with a double null mutation died shortl y after birth with open DAs. These results suggest that DA patency depends on circulating PGs acting on specific PG receptors within the DA. Collectiv ely, these findings demonstrate the coordinated regulation of fetal and mat ernal PGs at the time of birth but raise concern regarding the use of selec tive COX inhibitors for the management of preterm labor.