Grant: CIHR Fellowship

Preterm birth (PTB) is the most important problem in maternal-child health in North America, affecting 12.7% of pregnancies and accounting for 75% of all perinatal death. Moreover, very premature babies that survive have an incredibly high incidence of severe long-term health consequences and PTB is estimated to cost the health care system $26 billion annually (USA). Despite intense clinical and research efforts, PTB has actually increased over the past three decades. Our inability to reduce these rates has been attributed to our poor understanding of both the molecular events that trigger spontaneous PTB and the unknown role of genetic, cellular, and environmental factors that underlie the condition. As a result all current preventive measures, such as drugs designed to delay labour, are ineffective as they attempt to alleviate the overlying symptoms but do not address the primary mechanisms that cause premature delivery. In order to combat PTB a greater understanding of these processes is required; however, this has been (historically) hindered by a lack of suitable animal models available for PTB research. Recently, my graduate work and current postdoctoral laboratory independently produced the first spontaneous PTB mouse strains for premature birth studies. Using the uterine-specific p53 knockout mouse line, we have initiated a comprehensive study to examine the potential role of unregulated oxidative stress as an underlying factor leading to decidua cell senescence (irreversible growth arrest) and premature birth. Our preliminary analysis indicates that modulating the level of oxidative stress in pregnant uterine p53 knockout females can significantly influence the incidence of PTB in our susceptibility model; however, the precise mode of action remains to be elucidated. These first steps must be undertaken to develop effective clinical therapies to mitigate the climbing rate of premature birth and improve neonatal, infantile and long-term health of children.