Oxidative stress early in pregnancy and pregnancy outcome
ABSTRACT 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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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 · 3.63 Impact Factor
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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 · 1.53 Impact Factor
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ABSTRACT: Background: Micronucleus (MN) is a validated biomarker for DNA damage in peripheral blood lymphocytes (PBL) and is a reflection of the changes of human nutritional status. Folate (FA) and vitamin B12 are one-carbon metabolism-related micronutrients, which play important roles in maintaining genomic stability. Objective: To investigate the correcting effects of FA and B12 intervention on DNA damage in PBL. Method: One hundred fifty-six volunteers without history of cancer were divided into 5 age groups (20 - 69 y, 47.4 % male) for establishing the baseline of chromosomal damage by means of cytokinesis-block micronucleus assay. Twelve individuals whose MN frequency was higher than the median value in each age group were selected for a four-month FA (200 - 400 μg/day)-B12 (3.125 - 25 μg/day) intervention dosed as to age and MTHFR genotypes. Results: There were significantly positive correlations between age and MN frequency in all groups (p < 0.01). Among all age groups, the baseline MN frequencies were higher in females than that in males. The MN frequencies from 10 volunteers were reduced by 33.5 % after the intervention with the two micronutrients (p < 0.01), and two individuals did not show any changes. Conclusion: Dietary supplement intake of FA and B12 based on MTHFR genotypes could protect the genome from damage and benefit genome health.International Journal for Vitamin and Nutrition Research 12/2012; 82(6):374-382. DOI:10.1024/0300-9831/a000134 · 1.00 Impact Factor