Table_1_Phthalate Exposures, DNA Methylation and Adiposity in Mexican Children Through Adolescence.XLSX

Phthalates are a class of endocrine disrupting chemicals with near ubiquitous exposure to populations around the world. Phthalates have been associated with children's adiposity in previous studies, though discrepancies exist across studies that may be due to timing of exposure or outcome assessment and population differences (i.e., genetics, other confounders). DNA methylation, an epigenetic modification involved in gene regulation, may mediate the effects of early life phthalate exposures on health outcomes. This study aims to evaluate the mediating effect of DNA methylation at growth-related genes on the association between phthalate exposure and repeat measures of adiposity (BMI-for-age z-score, waist circumference, and skinfolds thickness) in Mexican children. Urinary phthalate metabolite concentrations were quantified in mothers at each of the three trimesters of pregnancy and in children at the first peri-adolescent study visit. Blood leukocyte DNA methylation at H19 and HSD11B2 was quantified during the first peri-adolescent visit, and adiposity was measured at the first visit and again ~3 years later among participants (n = 109 boys, 114 girls) from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) project. Associations between phthalates or DNA methylation and repeat outcome measures were assessed separately in boys and girls using generalized estimating equation models including covariates (urinary specific gravity, maternal education, and child's age). Sobel tests were used to assess DNA methylation as a mediator in models adjusting for the same covariates. Associations between phthalates and adiposity varied by phthalate and timing of exposure. Early gestation MBP, MIBP, and MBzP were associated with adiposity among girls. For example, among girls first trimester maternal urine concentrations of MIBP were associated with increases in skinfold thickness, BMI-for-age, and waist circumference (p 0.05). However, the mediation analysis was underpowered to detect small to medium effect sizes, and the role of DNA methylation as a mediator between phthalates and outcomes merits further study.</p

Associations between blood leukocyte DNA methylation and sustained attention in mid-to-late childhood

Supplementary figures 1 and 2Supplementary tables 1 and 2</p

Lead exposure induces changes in 5-hydroxymethylcytosine clusters in CpG islands in human embryonic stem cells and umbilical cord blood

<div><p>Prenatal exposure to neurotoxicants such as lead (Pb) may cause stable changes in the DNA methylation (5mC) profile of the fetal genome. However, few studies have examined its effect on the DNA de-methylation pathway, specifically the dynamic changes of the 5-hydroxymethylcytosine (5hmC) profile. Therefore, in this study, we investigate the relationship between Pb exposure and 5mC and 5hmC modifications during early development. To study the changes in the 5hmC profile, we use a novel modification of the Infinium™ HumanMethylation450 assay (Illumina, Inc.), which we named HMeDIP-450K assay, in an <i>in vitro</i> human embryonic stem cell model of Pb exposure. We model Pb exposure-associated 5hmC changes as clusters of correlated, adjacent CpG sites, which are co-responding to Pb. We further extend our study to look at Pb-dependent changes in high density 5hmC regions in umbilical cord blood DNA from 48 mother-infant pairs from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) cohort. For our study, we randomly selected umbilical cord blood from 24 male and 24 female children from the 1st and 4th quartiles of Pb levels. Our data show that Pb-associated changes in the 5hmC and 5mC profiles can be divided into sex-dependent and sex-independent categories. Interestingly, differential 5mC sites are better markers of Pb-associated sex-dependent changes compared to differential 5hmC sites. In this study we identified several 5hmC and 5mC genomic loci, which we believe might have some potential as early biomarkers of prenatal Pb exposure.</p></div

microRNA expression in the cervix during pregnancy is associated with length of gestation

<div><p>Preterm birth is a leading cause of infant mortality and can lead to poor life-long health and adverse neurodevelopmental outcomes. The pathophysiologic mechanisms that precede preterm labor remain elusive, and the role that epigenetic phenomena play is largely unstudied. The objective of this study was to assess the association between microRNA (miRNA) expression levels in cervical cells obtained from swabs collected during pregnancy and the length of gestation. We analyzed cervical samples obtained between 16 and 19 weeks of gestation from 53 women in a prospective cohort from Mexico City, and followed them until delivery. Cervical miRNA was extracted and expression was quantified using the NanoString nCounter Analysis System. Linear regression models were used to examine the association between miRNA expression levels and gestational age at delivery, adjusted for maternal age, education, parity, body mass index, smoke exposure, and inflammation assessed on a Papanicolaou smear. We identified 6 miRNAs that were significantly associated with gestational age at the time of delivery, including miR-21, 30e, 142, 148b, 29b, and 223. Notably, per each doubling in miR-21 expression, gestations were 0.9 (95% CI: 0.2–1.5) days shorter on average (<i>P</i> = 0.009). Per each doubling in miR-30e, 142, 148b, 29b, and 223 expression, gestations were shorter by 1.0 to 1.6 days. The predicted targets of the miRNAs were enriched for molecules involved in DNA replication and inflammatory processes. The levels of specific miRNAs in the human cervix during pregnancy are predictive of gestational age at delivery, and should be validated in future studies as potential biomarkers of preterm birth risk.</p></div