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Examination of Trace Metals and Their Potential Transplacental Transfer in Pregnancy.

ABSTRACT: With the ever-growing concern for human health and wellbeing, the prenatal period of development requires special attention since fetuses can be exposed to various metals through the mother. Therefore, this study explored the status of selected toxic (Pb, Cd, Ni, As, Pt, Ce, Rb, Sr, U) and essential trace metals (Mn, Co, Cu, Zn, Se) in the umbilical cord (UC) sera, maternal sera, and placental tissue samples of 92 healthy women with normal pregnancies. A further aim focuses on the potential transplacental transfer of these trace metals. Based on the obtained levels of investigated elements in clinical samples, it was observed that all of the trace metals cross the placental barrier and reach the fetus. Furthermore, statistical analysis revealed significant differences in levels of toxic Ni, As, Cd, U, Sr, Rb, and essential Mn, Cu, and Zn between all three types of analyzed clinical samples. Correlation analysis highlighted As to be an element with levels that differed significantly between all tested samples. Principal component analysis (PCA) was used to enhance these findings. PCA demonstrated that Cd, Mn, Zn, Rb, Ce, U, and Sr were the most influential trace metals in distinguishing placenta from maternal and UC serum samples. As, Co, and Cu were responsible for the clustering of maternal serum samples, and PCA demonstrated that the Pt level in UC sera was responsible for the clustering of these samples. Overall, the findings of this study could contribute to a better understanding of transplacental transfer of these trace metals, and shed a light on overall levels of metal exposure in the population of healthy pregnant women and their fetuses.

SUBMITTER: Jagodic J

PROVIDER: S-EPMC9330144 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundExposure to some toxic metals, such as lead and cadmium, has been associated with increased oxidative stress. However less is known about other metals and metal mixtures, especially in pregnant women who are a vulnerable population.MethodsTo study the relationship between exposure to trace metals and oxidative stress, we analyzed a panel of 17 metals and two oxidative stress biomarkers (8-isoprostane and 8-hydroxydeoxyguanosine [8-OHdG]) in urine samples collected at ~26 weeks gestation from pregnant women in Boston (n = 380). We used linear regression models to calculate percent differences and 95% confidence intervals (CI) in oxidative stress markers for an interquartile range (IQR) increase in each urinary metal with adjustment for other metals. In addition, we applied principal components analysis (PCA) and Bayesian kernel machine regression (BKMR), to examine cumulative effects (within correlated groups of exposures as well as overall) and interactions.ResultsWe estimated 109% (95% CI: 47, 198) higher 8-isoprostane and 71% (95% CI: 45, 102) higher 8-OHdG with an IQR increase in urinary selenium (Se). We also estimated higher 8-isoprostane (47%, 95% CI: 20.5, 79.4) and 8-OHdG (15.3%, 95% CI: 5.09, 26.5) in association with urinary copper (Cu). In our PCA, we observed higher 8-isoprostane levels in association with the "essential" PC (highly loaded by Cu, Se, and Zinc). In BKMR analyses, we also estimated higher levels of both oxidative stress biomarkers with increasing Se and Cu as well as increasing levels of both oxidative stress biomarkers in association with cumulative concentrations of urinary trace metals.ConclusionWe observed higher 8-isoprostane and 8-OHdG levels in association with urinary trace metals and elements, particularly Se and Cu, in linear models and using mixtures approaches. Additionally, increasing cumulative exposure to urinary trace metals was associated with higher levels of both oxidative stress biomarkers. The beneficial effects of these compounds should be carefully questioned.

Project description:ObjectiveThe objective of the study was to determine the bidirectional transfer of pravastatin across the dually perfused term human placental lobule and its distribution between the tissue and maternal and fetal circuits.Study designThe transfer of pravastatin was determined in the maternal-to-fetal (n = 11) and fetal-to-maternal (n = 10) directions. Pravastatin was coperfused with its [(3)H]-isotope and the marker compound antipyrine (20 μg/mL) and its [(14)C]-isotope. The concentration of pravastatin in the perfused tissue and the maternal and fetal circuits was determined using liquid scintillation spectrometry. Inside-out vesicles prepared from placental brush border membranes were utilized to investigate the role of efflux transporters in the transplacental transfer of pravastatin.ResultsPravastatin was transferred from the maternal to the fetal circuit and vice versa. In the maternal-to-fetal direction, the distribution of pravastatin at the end of experiment was as follows: 14 ± 5% of the drug was retained by the tissue, 68 ± 5% remained in the maternal circuit, and 18 ± 4% was transferred to the fetal circuit. The normalized transfer of pravastatin (clearance index) to antipyrine in the fetal-to-maternal direction (0.48 ± 0.07) was higher than its transfer in the maternal-to-fetal direction (0.36 ± 0.07, P < .01). Furthermore, pravastatin inhibited the adenosine triphosphate (ATP)-dependent uptake of the paclitaxel and estrone sulfate.ConclusionThe transfer of pravastatin across the dually perfused placental lobule suggests that fetal exposure to pravastatin is plausible. The higher transfer of pravastatin in the fetal-to-maternal direction than the reverse as well as its inhibition of the ATP-dependent uptake of [(3)H]-paclitaxel and [(3)H]-estrone sulfate strongly suggest the involvement of efflux transporters in decreasing its transfer across the placenta and support pravastatin's favorable pharmacokinetic profile in pregnancy.

Project description:BackgroundRecurrent pregnancy loss (RPL) was associated with an elevated risk of pregnancy complications, particularly preterm birth (PTB). However, the risk factors associated with PTB in RPL remained unclear. Emerging evidence indicated that maternal exposure to metals played a crucial role in the development of PTB. The objective of our study was to investigate the individual and combined associations of nutritional trace metals (NTMs) during pregnancy with PTB in RPL.MethodsUsing data from a recurrent pregnancy loss cohort (n = 459), propensity score matching (1:3) was performed to control for covariates. Multiple logistic regression and multiple linear regression were employed to identify the individual effects, while elastic-net regularization (ENET) and Bayesian kernel machine regression (BKMR) were used to examine the combined effects on PTB in RPL.ResultsThe logistic regression model found that maternal exposure to copper (Cu) (quantile 4 [Q4] vs. quantile 1 [Q1], odds ratio [OR]: 0.21, 95% confidence interval [CI]: 0.05, 0.74) and zinc (Zn) (Q4 vs. Q1, OR: 0.19, 95%CI: 0.04, 0.77) was inversely associated with total PTB risk. We further constructed environmental risk scores (ERSs) using principal components and interaction terms derived from the ENET model to predict PTB accurately (p < 0.001). In the BKMR model, we confirmed that Cu was the most significant component (PIP = 0.85). When other metals were fixed at the 25th and 50th percentiles, Cu was inversely associated with PTB. In addition, we demonstrated the non-linear relationships of Zn with PTB and the potential interaction between Cu and other metals, including Zn, Ca, and Fe.ConclusionIn conclusion, our study highlighted the significance of maternal exposure to NTMs in RPL and its association with PTB risk. Cu and Zn were inversely associated with PTB risk, with Cu identified as a crucial factor. Potential interactions between Cu and other metals (Zn, Ca, and Fe) further contributed to the understanding of PTB etiology in RPL. These findings suggest opportunities for personalized care and preventive interventions to optimize maternal and infant health outcomes.

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Examination of Trace Metals and Their Potential Transplacental Transfer in Pregnancy.

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