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DNA methylation (DNAm) is vulnerable to dysregulation by environmental exposures during epigenetic reprogramming that occurs in embryogenesis. Sexual dimorphism in environmentally induced DNAm dysregulation has been identified and therefore it is important to understand sex-specific DNAm patterns. DNAm at several autosomal sites has been consistently associated with sex in cord blood and placental foetal tissues. However, there is limited research comparing sex-specific DNAm across tissues, particularly differentially methylated regions (DMRs). This study leverages DNAm data measured using the Illumina HumanMethylation450 BeadChip in cord blood (N = 179), placenta (N = 229), and umbilical artery samples (N = 229) in the PRogramming of Intergenerational Stress Mechanisms (PRISM) cohort to identify autosomal DMRs and differentially methylated positions (DMPs). A replication analyses was conducted in an independent cohort (GEO Accession GSE129841). We identified 183, 257, and 419 DMRs and 2119, 2281, and 3405 DMPs (pBonferroni < 0.05) in cord blood, placenta, and artery samples, respectively. Thirty-nine DMRs overlapped in all three tissues, overlapping with genes involved in spermatogenesis (NKAPL, PIWIL2 and AURKC) and X–inactivation (LRIF1). In replication analysis, 85% of DMRs overlapped with those identified in PRISM. Overall, DMRs and DMPs had higher methylation levels among females in cord blood and artery samples, but higher methylation levels among males in placenta samples. Further research is necessary to understand biological mechanisms that contribute to differences in sex-specific DNAm signatures across tissues, as well as to determine if sexual dimorphism in the epigenome impacts response to environmental stressors. [ABSTRACT FROM AUTHOR]

Maternal stress is associated with adverse child health. Breast milk microRNAs encapsulated in extracellular vesicles (EVs) are involved in mother-infant biochemical communication during early-life programming. We leverage the PRogramming of Intergenerational Stress Mechanisms (PRISM) pregnancy cohort to investigate associations between maternal stress and breast milk EV-microRNAs. Lifetime stress and negative life events (NLEs) during pregnancy were assessed using the Life Stressor Checklist-Revised (LSCR) and the Crisis in Family Systems-Revised surveys, respectively. RNA was extracted from breast milk EVs (N = 80; collected 6.1 ± 5.9 weeks postnatally), and microRNAs were profiled using the TaqMan OpenArray Human miRNA panel. Associations between stress scores and detection (yes/no) of 173 microRNAs identified in 20–80% of samples were assessed using logistic regression; associations with expression levels of 205 EV-microRNAs identified in >50% of samples were assessed using linear regression. In adjusted models, detection of 60 and 44 EV-microRNAs was associated with higher LSCR and NLE scores, respectively (p < 0.05). Expression level of 8 and 17 EV-microRNAs was associated with LSCR and NLE scores, respectively, at our a priori criteria of p < 0.05 and |Bregression|>0.2. Enriched KEGG pathways for microRNAs associated with stress scores included fatty acid metabolism and the Hippo signaling pathway. Maternal lifetime stress and NLEs during pregnancy were both associated with detection and expression level of breast milk EV-microRNAs, although associations with microRNA profiles differed between stress measures. Further research is needed to identify biological pathways impacted by associated microRNAs and investigate relationships with child health outcomes. Abbreviations: EV: extracellular vesicle; PRISM: PRogramming of Intergenerational Stress Mechanisms pregnancy cohort; LSCR: Life Stressor Checklist-Revised survey; NLE: negative life event; CRISYS-R: Crisis in Family Systems-Revised survey; KEGG: Kyoto Encyclopaedia of Genes and Genomes; NYC: New York City; SD: standard deviation; IQR: interquartile range; Cq: relative cycle threshold values; PCA: principal component analysis [ABSTRACT FROM AUTHOR]

DNA methylation microarrays have been the platform of choice for epigenome-wide association studies in epidemiology, but declining costs have rendered targeted bisulphite sequencing a feasible alternative. Nonetheless, the literature for researchers seeking guidance on which platform to choose is sparse. To fill this gap, we conducted a comparison study in which we processed cord blood samples from four newborns in duplicates using both the Illumina HumanMethylationEPIC BeadChip and the Illumina TruSeq Methyl Capture EPIC Kit, and evaluated both platforms in regard to coverage, reproducibility, and identification of differential methylation. We conclude that with current analytic goals microarrays still outperform bisulphite sequencing for precise quantification of DNA methylation. [ABSTRACT FROM AUTHOR]