The effects of gestational age on placental oxidative balance throughout gestation were investigated in women with uncomplicated pregnancies. Placental tissues were obtained from normal pregnant women who delivered at term or underwent elective pregnancy termination at 6 to 23 + 6 weeks of pregnancy. Placental tissues were analyzed for total antioxidant capacity (TAC) and lipid peroxide (malondialdehyde, MDA) levels using commercially available kits. Two hundred and one placental tissues were analyzed and the mean ± SD MDA (pmol/mg tissue) and TAC (µmol Trolox equivalent/mg tissue) levels for first, second, and third trimester groups were 277.01 ± 204.66, 202.66 ± 185.05, and 176.97 ± 141.61, P < 0.004 and 498.62 ± 400.74, 454.90 ± 374.44, and 912.19 ± 586.21, P < 0.0001 by ANOVA, respectively. Our data reflects an increased oxidative stress in the placenta in the early phase of normal pregnancy. As pregnancy progressed, placental antioxidant protective mechanisms increased and lipid peroxidation markers decreased resulting in diminution in oxidative stress. Our findings provide a biochemical support to the concept of a hypoxic environment in early pregnancy. A decrease in placental oxidative stress in the second and third trimesters appears to be a physiological phenomenon of normal pregnancy. Deviations from this physiological phenomenon may result in placental-mediated disorders.

Variations in placental TNF-α protein expression noted at different trimesters may suggest gestational age specific roles for the cytokine. The increase in TNF-α protein expression observed in the second trimester may be involved in upregulating synthesis of MMP and in augmenting apoptosis of vascular smooth muscle cells of the spiral arteries. A failure in this second trimester increase in TNF-α protein could contribute to gestational compromise.

Matrix metalloproteinases (MMPs), specifically MMP-9 plays a role in human placentation. The enzyme confers an invasive ability to cytotrophoblasts and degrades the endometrial matrix as the cells infiltrate the decidua to keep up with placental growth. Since tumor necrosis factor-a (TNF-a) can induce the synthesis of MMP-9, we investigated the patterns of changes in and correlation between placental villous MMP-9 and TNF-a expressions throughout normal human gestation. Placentas were obtained from 179 normal pregnant women who underwent elective abortion or term delivery. Chorionic villi isolated from placental samples were grouped as first, second, and third trimester (7 0/7 -13 0/7 , 13 1/7 -23 6/7 , and 37 0/7 -42 4/7 weeks, respectively). Chorionic villous TNF-a and MMP-9 proteins were assayed using enzyme immunoassay kits. There were significant differences in MMP-9 and TNF-a protein expressions among the trimester groups (P ¼ .001). The MMP-9 protein increased progressively with an increase in gestational age (GA), but TNF-a peaked in the second trimester. Within each trimester group, we searched for the effects of variation of GA in days on the 2 variables. A significant positive correlation between MMP-9 and GA was noted in the first trimester (r ¼ 0.364, P ¼ .005). No other comparisons were significant. When GA was controlled for, partial correlation revealed a significant positive correlation between TNF-a and MMP-9 only in the second trimester (r ¼ 0.300, P ¼ .018). We hypothesize that the TNF-a peak and the positive correlation between TNF-a and MMP-9 in the second trimester of normal human gestation could contribute toward a successful pregnancy outcome.

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