Oxidative stress early in pregnancy and pregnancy outcome

Department of Surgery, University of Medicine and Dentistry of New Jersey-SOM, Stratford, NJ 08084, USA.
Free Radical Research (Impact Factor: 2.98). 11/2008; 42(10):841-8. DOI: 10.1080/10715760802510069
Source: PubMed


The objectives of this study were to determine whether oxidative stress early in pregnancy influenced pregnancy outcome. A combination of assays were used for exogenous and endogenous anti-oxidants together with two well accepted biomarkers for oxidative stress, the urinary excretion of 8-iso-PGF(2alpha) (a biomarker marker for lipid oxidation, n=508) and 8-oxo-7,8 dihydro-2 deoxyguanosine (8-OHdG, a biomarker for DNA oxidation, n=487). The two biomarkers tracked different pregnancy outcomes. Isoprostanes were associated with an increased risk of pre-eclampsia and a decreased proportion of female births. In contrast, 8-OHdG tracked lower infant birthweight and shortened gestation duration. Birth defects were associated with low levels of 8-OHdG.

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    • "The criteria for preeclampsia diagnosis are: a new onset of hypertension (blood pressure≥140/90 mmHg in previously normotensive women) and proteinuria (≥300 mg/24-hour urine collection or random urine protein (+)) after the 20th week of the pregnancy. The delivery of the baby and placenta is the only curative treatment to reverse the syndrome [2]. Because of the adverse outcome of this disease, continuously growing number of studies has been focusing on this area; however, the specific pathogenesis of this disorder remains to be elucidated. "
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    ABSTRACT: SPRY4-IT1 has been reported to have extremely high expression in normal placenta tissues. It is a Long noncoding RNA (lncRNA), which is associated with cell growth, migration, invasion, and apoptosis in melanoma. A 2.8-fold increase of SPRY4-IT1 expression was validated by Real-time reverse transcription-polymerase chain reaction (qRT-PCR) in severe preeclamptic placenta as compared with that of the normal ones (n=25) in this study. Furthermore, the role of SPRY4-IT1 in proliferation, migration, apoptosis, and network formation ability of trophoblast cells HTR-8/SVneo was assessed. Suppression of SPRY4-IT1 using siRNA treatment and its overexpression using plasmid targeting SPRY4-IT1 were performed in order to explore the biological function of SPRY4-IT1 in the development and progression of trophoblast cells HTR-8/SVneo, in vitro. The results showed that SPRY4-IT1 knockdown enhanced the cell migration and proliferation, and reduced the response of cells to apoptosis. However, exogenous SPRY4-IT1 overexpression significantly decreased the cell migration and proliferation, while increased cell apoptosis. Our study showed for the first time that aberrant expression of lncRNA SPRY4-IT1 might contribute to the abnormal condition of trophoblast cells HTR-8/SVneo. Therefore, we proposed SPRY4-IT1 as a novel lncRNA molecule, which might be associated with the pathogenesis of preeclampsia and might provide a new target for its early diagnosis and treatment.
    PLoS ONE 11/2013; 8(11):e79598. DOI:10.1371/journal.pone.0079598 · 3.23 Impact Factor
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    • "Studies published by Erkekoglu et al. demonstrate ROS generation and oxidative DNA damage with MEHP concentrations as low as 3 μM; however, the reason for detection of these effects with lower treatment concentrations is not known (Erkekoglu et al., 2010, 2011). Because urinary oxidative stress markers, including urinary 8-OHdG, a marker of oxidative DNA damage, are predictive of shortened gestation length and low birth weight, our findings may have relevance to adverse pregnancy outcomes (Peter Stein et al., 2008). "
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    ABSTRACT: Di-2-ethylhexyl phthalate (DEHP) is an environmental contaminant commonly used as a plasticizer in polyvinyl chloride products. Exposure to DEHP has been linked to adverse pregnancy outcomes in humans including preterm birth, low birth-weight, and pregnancy loss. Although oxidative stress is linked to the pathology of adverse pregnancy outcomes, effects of DEHP metabolites, including the active metabolite, mono-2-ethylhexyl phthalate (MEHP), on oxidative stress responses in placental cells has not been previously evaluated. The objective of the current study is to identify MEHP-stimulated oxidative stress responses in human placental cells. We treated a human placental cell line, HTR-8/SVneo, with MEHP and then measured reactive oxygen species (ROS) generation using the dichlorofluorescein assay, oxidized thymine with mass-spectrometry, redox-sensitive gene expression with qRT-PCR, and apoptosis using a luminescence assay for caspase 3/7 activity. Treatment of HTR-8 cells with 180 μM MEHP increased ROS generation, oxidative DNA damage, and caspase 3/7 activity, and resulted in differential expression of redox-sensitive genes. Notably, 90 and 180 μM MEHP significantly induced mRNA expression of prostaglandin-endoperoxide synthase 2 (PTGS2), an enzyme important for synthesis of prostaglandins implicated in initiation of labor. The results from the present study are the first to demonstrate that MEHP stimulates oxidative stress responses in placental cells. Furthermore, the MEHP concentrations used were within an order of magnitude of the highest concentrations measured previously in human umbilical cord or maternal serum. The findings from the current study warrant future mechanistic studies of oxidative stress, apoptosis, and prostaglandins as molecular mediators of DEHP/MEHP-associated adverse pregnancy outcomes.
    Toxicology and Applied Pharmacology 01/2013; 268(1). DOI:10.1016/j.taap.2013.01.020 · 3.71 Impact Factor
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    • "During normal human pregnancy, serum lipid peroxidation products are elevated but counterbalanced by an increased antioxidant activity (Buhimschi and Weiner, 2001). Increased maternal oxidative stress in early human pregnancy is associated with pre-eclampsia, shortened gestation duration , lower infant birth weight, and so forth (Stein et al., 2008). In our study, after 6-OHDA treatment, SOD and GPx activities were decreased (P < 0.05) in the maternal spleen during early pregnancy. "
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    ABSTRACT: Sympathetic regulation plays an important role in fetal survival and development during early pregnancy. Maternal adaptations to pregnancy may involve changes of the spleen in its structure, size, and function. This study was therefore designed to investigate the effects of sympathetic nerves on these adaptations in the maternal spleen of mice during early pregnancy. The adult female mice were intraperitoneally injected with neurotoxin 6-hydroxydopamine (6-OHDA) for 5 consecutive days to selectively destroy the sympathetic nerves. The results were as follows: (1) the splenic weight was reduced in the 6-OHDA group by 10.9%-13.0% at E5-E9 (P < 0.05) when compared with the control group. (2) The splenic nodule and periarterial lymphatic sheath of the 6-OHDA-treated mice were smaller than those of control mice. The proliferating cell nuclear antigen positive cells of 6-OHDA-treated group were decreased by 10.9%-16.2% (P < 0.05) at E1-E9. (3) Lymphocyte proliferation indices in response to concanavalin A or lipopolysaccharide were significantly decreased (P < 0.05) in the 6-OHDA group. (4) When compared with control mice, the superoxide dismutase and glutathione peroxidase activities of 6-OHDA-treated mice were decreased by 14.3%-21.9% (P < 0.05) at E1-E9 and 17.4%-25.0% (P < 0.05) at E3-E9, respectively. In contrast, the malondialdehyde content of 6-OHDA group was increased by 10.6%-38.6% (P < 0.05) at E3-E9. The results demonstrated the regulation of pregnancy-dependent adaptations in the spleen through the sympathetic nerve activity.
    The Anatomical Record Advances in Integrative Anatomy and Evolutionary Biology 05/2011; 294(5):875-82. DOI:10.1002/ar.21372 · 1.54 Impact Factor
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