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Inflammation is a physiologic component of pregnancy and parturition. Overwhelming intrauterine inflammatory load promotes quiescent feto-maternal tissues into a contractile phenotype. Like inflammation, oxidative stress is an inevitable component of both pregnancy and parturition. Pathologic activation of host innate immune response to adverse pregnancy conditions can lead to premature activation of inflammatory and oxidative stress. Inflammation and oxidative stress markers seen with both sterile and infectious inflammation are often similar; therefore, it is difficult to understand causality of conditions like spontaneous preterm birth. This review demonstrates potential mechanistic pathways of activation of sterile and infectious inflammation. We demonstrate the activation of two unique pathways of inflammation by factors that are well-documented proxies for oxidative stress (cigarette smoke extract) and infection (lipopolysaccharide). Sterile inflammation seen after exposure to an oxidative stress inducer is due to cellular elemental damage resulting in p38 mitogen-activated protein kinase (MAPK) induced cellular senescence. Infectious inflammation is through activation of transcription factor NF-κB and independent of oxidative stress-associated damages and p38 MAPK-induced senescence. Understanding the differences in the inflammatory pathway activation by various risk factors is important to design better screening, diagnostic and intervention strategies to reduce the risks of adverse pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Objective Polybrominated diphenyl ethers (PBDEs) are documented to increase the risk for spontaneous preterm birth ( PTB). We hypothesize that PBDEs cause oxidative stress ( OS) that leads to fetal cell senescence and inflammation associated with PTB. Methods Primary amnion epithelial cells ( n = 5) isolated from term, not in labor pregnancies, were exposed to PBDE congeners 47 and 99 (each 5 μ m). ROS kinetics was monitored. Morphologic changes, phospho-p38 MAPK (P-p38) activation, development of senescence, and induction of uterotonins ( COX-2 expression) were quantified using light microscopy, Western blot, senescence-associated β-galactosidase ( SA β-gal) staining, and qRT- PCR, respectively, after 48 and 72 hr of exposure. Results Both PBDE congeners induced ROS within 2 min compared to controls ( P < 0.05). P-p38 activation was significant after PBDE-99 treatment than controls ( P < 0.05). After 72 hr of treatment, both PBDE-treated cells showed cell death-associated morphologic changes with significantly higher SA β-gal-stained cells than control. COX-2 expression was higher after 72 hr of treatment with PBDE-99. Overall, the PBDE-99 response was more pronounced than PBDE-47. Conclusions Congener-dependent OS response, p38 MAPK activation, senescence, and COX-2 expression were seen in human amnion cells by PBDEs. These findings demonstrate environment pollutant-induced senescence activation and inflammation can lead to pathways resulting in PTB. [ABSTRACT FROM AUTHOR]