EC Gynaecology

Introduction and Objective: For over half a century, growing evidence has demonstrated that in pregnancies complicated with preeclampsia, plasma and placental concentrations of tumor necrosis factor-alpha (TNF- α) protein is significantly high. In preeclamptic tissues, TNF-α protein has been reported to be associated with lipid peroxidation product, malondialdehyde (MDA). Additionally, in normal human pregnancy, TNF-α protein is reported to induce the synthesis of placental protein matrix metalloproteinase-9 (MMP-9). In the present study, we determined the gestational age specific alterations in these three interconnected constituents: MDA, TNF-α protein and MMP-9 protein, and have additionally compared the placental parameters of normal pregnancy with that of preeclampsia.

Methods: Placental tissues were collected from normal pregnant women who underwent elective termination of pregnancy and from women who delivered at term. Placentas were also collected from women with preeclampsia, as diagnosed by ACOG's criteria. Chorionic villi were isolated from each placenta. Chorionic villi MDA was measured by the Thiobarbituric acid method; TNF-α and MMP-9 protein expressions were determined by enzyme linked immunoassays. For statistical analyses, one way analysis of variance (ANOVA), Independent T Test and Spearman's bivariate correlation were applied. P< 0.05 was considered significant.

Results: 212 placentas were analyzed: 179 from uncomplicated pregnancies and 33 from preeclampsia. In normal pregnancy, the three chorionic villi constituents showed gestational age-specific profiles. Suppression of MDA levels were noted with advance in gestational age. MDA levels were 299.79 ± 312.52, 205.71 ± 157.07, and 183.93 ± 141.39 pmol/mg tissue in the first, second and third trimester, respectively. TNF-α protein showed a mid-gestational peak and the protein expression were 36.22 ± 18.59, 55.64 ± 43.66, 29.35 ± 33.61 pg/100 mg tissue in the first, second and third trimester, respectively. For MMP-9 protein, a progressive increase in protein expression was seen with increase in gestational age (20.32 ± 12.64, 22.75 ± 13.35, 28.82 ± 11.12 ng/100 mg tissue for first, second and third trimester, respectively). The chorionic villi MDA levels of the preeclampsia group were comparable to the first trimester group of normal pregnancy. The chorionic villi TNF- α protein levels in preeclampsia paralleled that of the second trimester group, and the chorionic villi MMP-9 protein levels surpassed that of the third trimester values. In the first trimester, TNF-α protein and MMP-9 protein were significantly correlated (r = 0.337, p = 0.013). A positive correlation was seen between MMP-9 protein and gestational age (r = 0.501, p = 0.000). Maternal age and maternal systolic blood pressure (r = 0.296, p = 0.03) were significantly correlated. In the second trimester, TNF-α protein and MDA levels were negatively correlated (r = -0.284, p = 0.019); and MMP-9 protein was significantly correlated with both maternal systolic (r = 0.326, p = 0.007) and diastolic blood pressure (r = 0.314, p = 0.009). No correlation was seen between the studied biochemical constituents in the third trimesters of normal pregnancy or in preeclampsia. Maternal systolic and diastolic blood pressure showed significant correlation at all trimesters of normal pregnancy and in preeclampsia (p < 0.0001).

Conclusion: In normal pregnancy, the findings show that MDA levels and TNF-α protein expression taper off in the third trimester. In preeclampsia, however, the exacerbated state persists. The data imply that the physiological brake (s) that operates as the pregnancy enters the third trimester may perhaps be lost in preeclampsia. Interactions seen between TNF-α protein with MDA or MMP-9 protein indicate a possible regulatory role for the cytokine in normal pregnancy. The findings support the concept that human pregnancy is not a single event. The findings highlight that for a successful pregnancy outcome, the gestational age-specific alterations in the levels of the studied constituents, as well as the specific correlations between the studied biochemical parameters are important for the various pregnancy-related processes to transpire.

Keywords: Pregnancy-Specific Protein Expressions; Normal Human Pregnancy; Preeclampsia; MDA; TNF-α and MMP-9 Proteins

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