title: p38 Mitogen activated protein kinase (MAPK): a new therapeutic target for reducing the risk of adverse pregnancy outcomes.
abstract: Spontaneous preterm birth (PTB) and preterm premature rupture of the membranes (pPROM) remain as a major clinical and therapeutic problem for intervention and management. Current strategies, based on our knowledge of pathways of preterm labor, have only been effective, in part, due to major gaps in our existing knowledge of risks and risk specific pathways. Areas covered: Recent literature has identified physiologic aging of fetal tissues as a potential mechanistic feature of normal parturition. This process is affected by telomere dependent and p38 mitogen activated protein kinase (MAPK) induced senescence activation. Pregnancy associated risk factors can cause pathologic activation of this pathway that can cause oxidative stress induced p38 MAPK activation leading to senescence and premature aging of fetal tissues. Premature aging is associated with sterile inflammation capable of triggering preterm labor or preterm premature rupture of membranes. Preterm activation of p38MAPK can be considered as a key contributor to adverse pregnancies. Expert opinion: This review considers p38MAPK activation as a potential target for therapeutic interventions to prevent adverse pregnancy outcomes mediated by stress factors. In this review, we propose multiple strategies to prevent p38MAPK activation.
authors.affiliation: a Division of Maternal-Fetal Medicine and Perinatal Research, Department of Obstetrics and Gynecology , The University of Texas Medical Branch at Galveston , Galveston , TX , USA.
authors.forename: Ramkumar
authors.initials: R
authors.lastname: Menon
authors.affiliation: b Department of Biochemistry and Molecular Biology , The University of Texas Medical Branch at Galveston , Galveston , TX , USA.
authors.forename: John
authors.initials: J
authors.lastname: Papaconstantinou
mesh_terms: D000818:Animals; D005260:Female; D005322:Premature Rupture of Fetal Membranes / Q000517:prevention & control*; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology; D011247:Pregnancy; D011256:Pregnancy Outcome; D047928:Premature Birth / Q000517:prevention & control*; D012307:Risk Factors; D016615:Telomere / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D048051:p38 Mitogen-Activated Protein Kinases
keywords: Preterm birth; aging; interventions; oxidative stress; pregnancy and child birth; premature rupture of membranes; senescence; sterile inflammation