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In utero metal exposures measured in deciduous teeth and birth outcomes in a racially-diverse urban cohort.

ABSTRACT: A growing number of studies have examined associations of metal exposures with birth outcomes, however, results from these studies have been inconsistent, and hampered by methodological limitations. We measured direct fetal exposure to three metals (lead, manganese and zinc) during the second and third trimester and examined its association with birth weight and gestational age at delivery. Participants in the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study (WHEALS), a population-based birth cohort established between September 2003 and December 2007, were invited to donate teeth to the study. Lead, manganese and zinc during the second and third trimesters were measured via high-resolution microspatial mapping of dentin growth rings, a validated biomarker for prenatal metal exposure. Gestational age at delivery and infant birth weight were obtained from the delivery medical record. A total of 145 children had tooth metal measurements and birth outcome data. Mean birth weight was 3431?±?472?g and mean gestational age at delivery was 39.0?±?1.3 weeks. Overall, there was a positive association between second (??=?0.21, 95% CI: 0.05, 0.37, P?=?0.01) and third trimester (??=?0.21, 95% CI: 0.05, 0.37, P?=?0.01) tooth manganese and birth weight Z-score; this remained statistically significant after covariate adjustment. There was also a negative association between second trimester tooth lead level and birth weight Z-score (??=?-0.20, 95% CI: -0.38, -0.02, P?=?0.02), however, this was attenuated after adjusting for covariates. Mixture analysis revealed similar findings. There was evidence for a sex-specific effect of manganese with birth weight Z-score, with the association stronger in female compared to male infants. Overall, we found evidence suggesting that higher in utero manganese is associated with larger birth weight Z-scores and that these associations may vary by infant sex.

SUBMITTER: Cassidy-Bushrow AE

PROVIDER: S-EPMC6402585 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

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In utero metal exposures measured in deciduous teeth and birth outcomes in a racially-diverse urban cohort.

Cassidy-Bushrow Andrea E AE Wu Kuan-Han Hank KH Sitarik Alexandra R AR Park Sung Kyun SK Bielak Lawrence F LF Austin Christine C Gennings Chris C Curtin Paul P Johnson Christine Cole CC Arora Manish M

Environmental research 20190131

A growing number of studies have examined associations of metal exposures with birth outcomes, however, results from these studies have been inconsistent, and hampered by methodological limitations. We measured direct fetal exposure to three metals (lead, manganese and zinc) during the second and third trimester and examined its association with birth weight and gestational age at delivery. Participants in the Wayne County Health, Environment, Allergy and Asthma Longitudinal Study (WHEALS), a po ...[more]

PMID: 30735952

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Project description:BackgroundExposure to metals lead (Pb), mercury (Hg), and cadmium (Cd) and trace elements selenium (Se) and manganese (Mn) has been linked to the developmental origins of cardiometabolic diseases, but the mechanisms are not well-understood.ObjectiveConduct a metabolome-wide association study to understand how in utero exposure to Pb, Hg, Cd, Se, and Mn affects the metabolic programming of fetuses.MethodsWe used data from the Boston Birth Cohort, which enrolled mother-child pairs from Boston, MA. We measured metals and trace elements in maternal red blood cells (RBCs) collected 24-72 h after delivery, and metabolites in cord blood collected at birth. We used multivariable linear regression to examine associations of metals and trace elements with metabolites and Bonferroni correction to account for multiple comparisons. We assessed non-linear associations of metals and trace elements with metabolites using restricted cubic spline plots.ResultsThis analysis included 670 mother-child pairs (57% non-Hispanic Black and 24% Hispanic). After Bonferroni correction, there were 25 cord metabolites associated with at least one of the metals or trace elements. Pb was negatively associated with the xenobiotic piperine, Cd was positively associated with xenobiotics cotinine and hydroxycotinine, and Hg was associated with 8 lipid metabolites (in both directions). Se and Mn shared associations with 6 metabolites (in both directions), which mostly included nucleotides and amino acids; Se was additionally associated with 7 metabolites (mostly amino acids, nucleotides, and carnitines) and Mn was additionally associated with C36:4 hydroxy phosphatidylcholine. Restricted cubic spline plots showed that most associations were linear.DiscussionMaternal RBC metal and trace element concentrations were associated in a dose-dependent fashion with cord blood metabolites. What remains to be determined is whether these metals- and trace elements-associated changes in cord metabolites can influence a child's risk of cardiometabolic diseases.

Project description:Deciduous and permanent human teeth represent a model system to study ageing of mesenchymal populations. Aging is tightly connected to self-renewal and proliferation and thus, mapping potential molecular differences in these characteristics between populations constitutes an important task. Specifically designed microarray panels were used. We have detected a number of molecules that were differentially expressed in dental pulp mesenchyme from deciduous and permanent teeth extracted from young children and adults, respectively. Among the differentially regulated genes HMGA2, a stem cell-associated marker, stood out as a remarkable example with a robust expression in deciduous pulp cells. In addition to this, we discovered that several proliferation-related genes, including CDC2A and CDK4, were up-regulated in deciduous pulp cells, while matrix genes COL1A1, fibronectin and several signaling molecules, such as VEGF, FGFr-1 and IGFr-1 were up-regulated in the pulp cells from permanent teeth. Taken together, our data suggest that deciduous pulp cells are more robust in self- renewal and proliferation, whereas adult dental pulp cells are more capable of signaling and matrix synthesis. The deciduous teeth were collected from 3-12-year-old children (N=8), whereas the permanent teeth were collected from adults, 19-52 years of age (N=8). The tooth was mechanically separated into two halves to remove all soft tissue in the pulp. The pulp tissue was digested and the dissociated cells were passed through cell strainer and plated with culture medium. The cells were then passaged at 90% confluency to a 10 cm dish for expansion. RNA was extracted from passage one cells with the Qiagen RNeasy Mini Kit. Microarray analysis was performed using PIQORTM Stem Cell Microarray chip (Miltenyi Biotech), which is comprised of 942 relevant genes for stem/progenitor cells and key genes for cell differentiation, to identify gene sets that are differentially expressed between cells in the deciduous and adult teeth. A total of 1 μg RNA for each sample was used for amplification and further analysis with the PIQORTM stem cell microarray chip (Miltenyi Biotec), followed by detection with a laser scanner (Agilent Technologies). In total, 8 comparisons were performed with dataset consisting of two microarrays, each containing a total of 11 slides with signal intensities within the R/Bioconductor statistical framework. The Linear Model for Microarray Data package (Limma) was used to pre-process the raw data, perform quality controls and estimate statistical significance. Expression intensities were background-corrected using a convolution of normal and exponential distributions with an offset of 50, which were then normalized within every slide using loess normalization. We analyzed the red and green channels separately using the mixed model method and different groups were quantile-normalized separately. The correlation was computed between the two channels for the same spot. Differentially expressed genes were identified by computing the contrasts, fitting to a linear model, performing the hypothesis tests, and correcting for multiple testing by performing the false discovery rate using the Benjamini-Hochberg correction.

Project description:Background and objectivesDental cementum (DC) is a mineralized tissue covering tooth roots that plays a critical role in dental attachment. Differences in deciduous vs. permanent tooth DC have not been explored. We hypothesized that proteomic analysis of DC matrix would identify compositional differences in deciduous (DecDC) vs. permanent (PermDC) cementum that might reflect physiological or pathological differences, such as root resorption that is physiological in deciduous teeth but can be pathological in the permanent dentition.MethodsProtein extracts from deciduous (n = 25) and permanent (n = 12) teeth were pooled (five pools of DecDC, five teeth each; four pools of PermDC, three teeth each). Samples were denatured, and proteins were extracted, reduced, alkylated, digested, and analyzed by liquid chromatography-mass spectrometry (LC-MS/MS). The beta-binomial statistical test was applied to normalized spectrum counts with 5% significance level to determine differentially expressed proteins. Immunohistochemistry was used to validate selected proteins.ResultsA total of 510 proteins were identified: 123 (24.1%) exclusive to DecDC; 128 (25.1%) exclusive to PermDC; 259 (50.8%) commonly expressed in both DecDC and PermDC. Out of 60 differentially expressed proteins, 17 (28.3%) were detected in DecDC, including myeloperoxidase (MPO), whereas 43 (71.7%) were detected in PermDC, including decorin (DCN) and osteocalcin (BGLAP). Overall, Gene Ontology (GO) analysis indicated that all expressed proteins were related to GO biological processes that included localization and response to stress, and the GO molecular function of differentially expressed proteins was enriched in cell adhesion, molecular binding, cytoskeletal protein binding, structural molecular activity, and macromolecular complex binding. Immunohistochemistry confirmed the trends for selected differentially expressed proteins in human teeth.ConclusionsClear differences were found between the proteomes of DecDC and PermDC. These findings may lead to new insights into developmental differences between DecDC and PermDC, as well as to a better understanding of physiological/pathological events such as root resorption.

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In utero metal exposures measured in deciduous teeth and birth outcomes in a racially-diverse urban cohort.

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In utero metal exposures measured in deciduous teeth and birth outcomes in a racially-diverse urban cohort.

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