ABSTRACT
A growing body of evidence suggests that prenatal environment is important in Autism Spectrum Disorder (ASD) etiology. In this study, we compare placental shape features in younger siblings of children with ASD, who themselves are at high ASD risk, to a sample of low risk peers. Digital photographs of the fetal placenta surface and of the sliced placental disk from 129 high ASD risk newborns and from 267 newborns in the National Children's Study Vanguard pilot were analysed to extract comparable measures of placental chorionic surface shape, umbilical cord displacement and disk thickness. Placental thickness measures were moderately higher in siblings of ASD cases. The placentas of ASD-case siblings were also rounder and more regular in perimeter than general population placentas. After stratification by sex, these across-group differences persisted for both sexes but were more pronounced in females. No significant differences were observed in cord insertion measures. Variations in placental shape features are generally considered to reflect flexibility in placental growth in response to changes in intrauterine environment as the placenta establishes and matures. Reduced placental shape variability observed in high ASD risk siblings compared to low-risk controls may indicate restricted ability to compensate for intrauterine changes.
Subject(s)
Autism Spectrum Disorder/pathology , Placenta/pathology , Autistic Disorder/pathology , Case-Control Studies , Cohort Studies , Female , Humans , Infant, Newborn , Male , Organ Size , Photography , Placenta/abnormalities , Pregnancy , Risk Factors , Siblings , Umbilical Cord/abnormalities , Umbilical Cord/pathologyABSTRACT
BACKGROUND: The association between human blood DNA global methylation and global hydroxymethylation has not been evaluated in population-based studies. No studies have evaluated environmental determinants of global DNA hydroxymethylation, including exposure to metals. OBJECTIVE: We evaluated the association between global DNA methylation and global DNA hydroxymethylation in 48 Strong Heart Study participants for which selected metals had been measured in urine at baseline and DNA was available from 1989-1991 (visit 1) and 1998-1999 (visit 3). METHODS: We measured the percentage of 5-methylcytosine (5-mC) and 5-hydroxymethylcytosine (5-hmC) in samples using capture and detection antibodies followed by colorimetric quantification. We explored the association of participant characteristics (i.e., age, adiposity, smoking, and metal exposure) with both global DNA methylation and global DNA hydroxymethylation. RESULTS: The Spearman's correlation coefficient for 5-mC and 5-hmC levels was 0.32 (p = 0.03) at visit 1 and 0.54 (p < 0.001) at visit 3. Trends for both epigenetic modifications were consistent across potential determinants. In cross-sectional analyses, the odds ratios of methylated and hydroxymethylated DNA were 1.56 (95% CI: 0.95, 2.57) and 1.76 (95% CI: 1.07, 2.88), respectively, for the comparison of participants above and below the median percentage of dimethylarsinate. The corresponding odds ratios were 1.64 (95% CI: 1.02, 2.65) and 1.16 (95% CI: 0.70, 1.94), respectively, for the comparison of participants above and below the median cadmium level. Arsenic exposure and metabolism were consistently associated with both epigenetic markers in cross-sectional and prospective analyses. The positive correlation of 5-mC and 5-hmC levels was confirmed in an independent study population. CONCLUSIONS: Our findings support that both epigenetic measures are related at the population level. The consistent trends in the associations between these two epigenetic modifications and the characteristics evaluated, especially arsenic exposure and metabolism, suggest the need for understanding which of the two measures is a better biomarker for environmental epigenetic effects in future large-scale epidemiologic studies.
