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 h as yielded insight into the mechanisms that enhance fetal survival. An esse ntial role for glucocorticoids in promoting lung maturation sufficient for viability ex utero before the onset of normal parturition has been demonstr ated in corticotropin-releasing hormone-deficient mice. In contrast, matern al deficiency in the prostaglandin synthetic enzyme cyclooxygenase-1 result s in the markedly delayed onset of labor and fetal demise because of postda tes gestation. The complex interplay of factors that govern the onset of la bor is highlighted by mice deficient in both cyclooxygenase-1 and oxytocin. Whereas mice deficient in oxytocin demonstrate normal parturition, simulta neous cyclooxygenase-1 and oxytocin deficiency rescues the delayed onset of labor found in cyclooxygenase-1 knock-out mice but results in the prolonge d duration of labor. The consequences of complete deficiency of molecules i nvolved in parturition in mice suggest novel interventions for human preter m labor.