Oxidative stress in development: nature or nurture?

Department of Pediatrics, University of Pennsylvania School of Medicine, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
Free Radical Biology and Medicine (Impact Factor: 5.27). 10/2010; 49(7):1147-51. DOI: 10.1016/j.freeradbiomed.2010.07.011
Source: PubMed

ABSTRACT An unavoidable consequence of aerobic respiration is the generation of reactive oxygen species (ROS). These may negatively impact development. Nevertheless, a certain amount of oxidative stress is required to allow for the normal progression of embryonic and fetal growth. Alterations in placental oxidative stress results in altered placental function and ultimately altered fetal growth and/or developmental programming leading to long-term consequences into adulthood. This article reviews the role of redox in fetal development and will focus on how developmental programming is influenced by the fetal and placental redox state as well as discuss potential therapeutic interventions.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Normal term and spontaneous preterm births (PTB) are documented to be associated with oxidative stress (OS), and imbalances in the redox system (balance between pro- and antioxidant) have been reported in the maternal–fetal intrauterine compartments.The exact mechanism of labor initiation either at term or preterm by OS is still unclear, and this lack of understanding can partially be blamed for failure of antioxidant supplementation trials in PTB prevention. Based on recent findings from our laboratory, we postulate heterogeneity in host OS response. The physiologic (at term) and pathophysiologic (preterm) pathways of labor are not mediated by OS alone but by OS-induced damage to intrauterine tissues, especially fetal membranes of the placenta. OS damage affects all major cellular elements in the fetal cells, and this damage promotes fetal cell senescence (aging). The aging of the fetal cells is predominated by p38 mitogen activated kinase (p38MAPK) pathways. Senescing cells generate biomolecular signals that are uterotonic, triggering labor process. The aging of fetal cells is normal at term. However, aging is premature in PTB, especially in those PTBs complicated by preterm premature rupture of the membranes, where elements of redox imbalances and OS damage are more dominant. We postulate that fetal cell senescence signals generated by OS damage are likely triggers for labor. This review highlights the mechanisms involved in senescence development at term and preterm by OS damage and provides insight into novel fetal signals of labor initiation pathways.
    Frontiers in Immunology 11/2014; 5(567):1-14. DOI:10.3389/fimmu.2014.00567
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Life-history traits are often involved in trade-offs whose outcome would depend on the availability of resources but also on the state of specific molecular signals. Early conditions can influence trade-offs and program the phenotype throughout the lifetime, with oxidative stress likely involved in many taxa. Here we address the potential regulatory role of a single intracellular antioxidant in life history trade-offs. Blood glutathione levels were reduced in a large sample of birds (zebra finch Taeniopygia guttata) during development using the synthesis inhibitor buthionine sulfoximine (BSO). Results revealed several modifications in the adult phenotype. BSO-treated nestlings showed lower glutathione and plasma antioxidant levels. In adulthood, BSO birds endured greater oxidative damage in erythrocytes but stronger expression of a sexual signal. Moreover, adult BSO females also showed weaker resistance to oxidative stress but were heavier and showed better body condition. Results suggest that low glutathione values during growth favor the investment in traits that should improve fitness returns, probably in the form of early reproduction. Higher oxidative stress in adulthood may be endured if this cost is paid later in life. Either the presence of specific signaling mechanisms or the indirect effect of increased oxidative stress can explain our findings.
    The American Naturalist 03/2015; DOI:10.1086/679613 · 4.45 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Oxidative stress caused by elevated reactive oxygen species (ROS) is one of the predominant causes of both male and female infertility. Oxidative stress conditions cause either cell death or senescence by oxidation of cellular molecules including nucleic acid, proteins, and lipids. It is particularly important to minimize oxidative stress when in vitro fertilization is performed for the purpose of assisted reproduction. The problems associated with assisted reproductive technology are becoming evident, and it is now the time to clarify its mechanisms and cope with them. On the other hand, the beneficial roles of ROS, such as intracellular signaling, have become evident. The antithetical functions of ROS make it more difficult to overcome the problems caused by oxidative stress. Despite the difficulty in understanding mammalian reproduction, the mechanisms and problems can be gradually unveiled by advanced technology such as genetic modification of animals.
    Reproductive Medicine and Biology 04/2013; 13(2):71-79. DOI:10.1007/s12522-013-0170-0