Genetic analysis of fetal development and parturition control in the mouse

The application of targeted gene inactivation methodologies to the study of late fetal development and control of the timing for parturition in mice has yielded insight into the mechanisms that enhance fetal survival. An essential role for glucocorticoids in promoting lung maturation sufficient for viability ex utero before the onset of normal parturition has been demonstrated in corticotropin-releasing hormone-deficient mice. In contrast, maternal deficiency in the prostaglandin synthetic enzyme cyclooxygenase-1 results in the markedly delayed onset of labor and fetal demise because of postdates gestation. The complex interplay of factors that govern the onset of labor is highlighted by mice deficient in both cyclooxygenase-1 and oxytocin. Whereas mice deficient in oxytocin demonstrate normal parturition, simultaneous cyclooxygenase-1 and oxytocin deficiency rescues the delayed onset of labor found in cyclooxygenase-1 knockout mice but results in the prolonged duration of labor. The consequences of complete deficiency of molecules involved in parturition in mice suggest novel interventions for human preterm labor.