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Oxidative stress damage as a detrimental factor in preterm birth pathology.

Menon R - Front Immunol (2014)

Bottom Line: 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.Senescing cells generate biomolecular signals that are uterotonic, triggering labor process.The aging of fetal cells is normal at term.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, School of Medicine, The University of Texas Medical Branch , Galveston, TX , USA.

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.

No MeSH data available.


Related in: MedlinePlus

As depicted in this figure, preterm labor (the innermost circle) is an end result of multitudes of complex interacting pathologies and pathophysiologic pathways. The external layer (the outermost circle) shows static risk factors, including epidemiologic and genetic risk factors, that can lead to multiple disease processes as depicted in the middle circle. Epigenetic markers can be dynamic, and that complex interaction between the host environment and risk factors can produce epigenetic changes, which can lead to diseases contributing to final effecter pathways (the blue shaded area). Various diseases may also cause epigenetic changes in the genes of preterm labor pathways. Spontaneous preterm labor leading to preterm birth is a complex syndrome comprising multiple diseases, each of which can be independent initiators of labor-inducing pathways. All these disease processes can trigger inflammation and oxidative stress (OS). However, the extent and biomolecular characteristics of inflammation and OS are dependent on the type of risk that initiated the process, their complex interactions with the genetic–epigenetic system, and the disease that they cause. The final terminal pathways that involve inflammation and OS trigger labor-inducing signals from fetal membranes and decidua and cause cervical ripening, myometrial contractions, and membrane rupture, resulting in preterm labor and delivery. *Any exogenous factor that can impact pregnancy outcomes. Many of the static risk factors in the outer circles are also called environments.
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Figure 1: As depicted in this figure, preterm labor (the innermost circle) is an end result of multitudes of complex interacting pathologies and pathophysiologic pathways. The external layer (the outermost circle) shows static risk factors, including epidemiologic and genetic risk factors, that can lead to multiple disease processes as depicted in the middle circle. Epigenetic markers can be dynamic, and that complex interaction between the host environment and risk factors can produce epigenetic changes, which can lead to diseases contributing to final effecter pathways (the blue shaded area). Various diseases may also cause epigenetic changes in the genes of preterm labor pathways. Spontaneous preterm labor leading to preterm birth is a complex syndrome comprising multiple diseases, each of which can be independent initiators of labor-inducing pathways. All these disease processes can trigger inflammation and oxidative stress (OS). However, the extent and biomolecular characteristics of inflammation and OS are dependent on the type of risk that initiated the process, their complex interactions with the genetic–epigenetic system, and the disease that they cause. The final terminal pathways that involve inflammation and OS trigger labor-inducing signals from fetal membranes and decidua and cause cervical ripening, myometrial contractions, and membrane rupture, resulting in preterm labor and delivery. *Any exogenous factor that can impact pregnancy outcomes. Many of the static risk factors in the outer circles are also called environments.

Mentions: Risk factors of PTB and pPROM can be classified into two major categories, static and dynamic. As shown in Figure 1, all the risk factors outlined in the outermost layer can be called static risk factors as they are unlikely to change during the course of pregnancy. Independently or in combination, these static risk factors can either predispose or cause the dynamic risk factors that are commonly diagnosed as clinical risks or pathologies associated with adverse pregnancy outcomes. Epigenetic changes that are independent of DNA base variations generated by complex interactions between various risk factors during pregnancy can also contribute to dynamic clinical risks by altering expression of certain genes. These changes can transition between static and dynamic risks. Static and dynamic risk factors produce pathways and pathophysiologies depicted in the inner circle with a unique biomarker profile contributing to labor-inducing changes, resulting in PTB or pPROM. The final effector pathways culminating in labor and delivery include inflammation and oxidative stress (OS). In normal pregnancies, these are generated by various fetal and maternal factors that signal the end of pregnancy. In PTB, the maternal–fetal signals and their causal origins are still unclear as they arise from complex etiologies and redundant pathways.


Oxidative stress damage as a detrimental factor in preterm birth pathology.

Menon R - Front Immunol (2014)

As depicted in this figure, preterm labor (the innermost circle) is an end result of multitudes of complex interacting pathologies and pathophysiologic pathways. The external layer (the outermost circle) shows static risk factors, including epidemiologic and genetic risk factors, that can lead to multiple disease processes as depicted in the middle circle. Epigenetic markers can be dynamic, and that complex interaction between the host environment and risk factors can produce epigenetic changes, which can lead to diseases contributing to final effecter pathways (the blue shaded area). Various diseases may also cause epigenetic changes in the genes of preterm labor pathways. Spontaneous preterm labor leading to preterm birth is a complex syndrome comprising multiple diseases, each of which can be independent initiators of labor-inducing pathways. All these disease processes can trigger inflammation and oxidative stress (OS). However, the extent and biomolecular characteristics of inflammation and OS are dependent on the type of risk that initiated the process, their complex interactions with the genetic–epigenetic system, and the disease that they cause. The final terminal pathways that involve inflammation and OS trigger labor-inducing signals from fetal membranes and decidua and cause cervical ripening, myometrial contractions, and membrane rupture, resulting in preterm labor and delivery. *Any exogenous factor that can impact pregnancy outcomes. Many of the static risk factors in the outer circles are also called environments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4228920&req=5

Figure 1: As depicted in this figure, preterm labor (the innermost circle) is an end result of multitudes of complex interacting pathologies and pathophysiologic pathways. The external layer (the outermost circle) shows static risk factors, including epidemiologic and genetic risk factors, that can lead to multiple disease processes as depicted in the middle circle. Epigenetic markers can be dynamic, and that complex interaction between the host environment and risk factors can produce epigenetic changes, which can lead to diseases contributing to final effecter pathways (the blue shaded area). Various diseases may also cause epigenetic changes in the genes of preterm labor pathways. Spontaneous preterm labor leading to preterm birth is a complex syndrome comprising multiple diseases, each of which can be independent initiators of labor-inducing pathways. All these disease processes can trigger inflammation and oxidative stress (OS). However, the extent and biomolecular characteristics of inflammation and OS are dependent on the type of risk that initiated the process, their complex interactions with the genetic–epigenetic system, and the disease that they cause. The final terminal pathways that involve inflammation and OS trigger labor-inducing signals from fetal membranes and decidua and cause cervical ripening, myometrial contractions, and membrane rupture, resulting in preterm labor and delivery. *Any exogenous factor that can impact pregnancy outcomes. Many of the static risk factors in the outer circles are also called environments.
Mentions: Risk factors of PTB and pPROM can be classified into two major categories, static and dynamic. As shown in Figure 1, all the risk factors outlined in the outermost layer can be called static risk factors as they are unlikely to change during the course of pregnancy. Independently or in combination, these static risk factors can either predispose or cause the dynamic risk factors that are commonly diagnosed as clinical risks or pathologies associated with adverse pregnancy outcomes. Epigenetic changes that are independent of DNA base variations generated by complex interactions between various risk factors during pregnancy can also contribute to dynamic clinical risks by altering expression of certain genes. These changes can transition between static and dynamic risks. Static and dynamic risk factors produce pathways and pathophysiologies depicted in the inner circle with a unique biomarker profile contributing to labor-inducing changes, resulting in PTB or pPROM. The final effector pathways culminating in labor and delivery include inflammation and oxidative stress (OS). In normal pregnancies, these are generated by various fetal and maternal factors that signal the end of pregnancy. In PTB, the maternal–fetal signals and their causal origins are still unclear as they arise from complex etiologies and redundant pathways.

Bottom Line: 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.Senescing cells generate biomolecular signals that are uterotonic, triggering labor process.The aging of fetal cells is normal at term.

View Article: PubMed Central - PubMed

Affiliation: Department of Obstetrics and Gynecology, School of Medicine, The University of Texas Medical Branch , Galveston, TX , USA.

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.

No MeSH data available.


Related in: MedlinePlus