Prenatal lead exposure, telomere length in cord blood, and DNA methylation age in the PROGRESS prenatal cohort.

BACKGROUND: Lead is a ubiquitous pollutant with deleterious effects on human health and remains a major current public health concern in developing countries. This heavy metal may interfere with nucleic acids via oxidative stress or epigenetic changes that affect biological markers of aging, e.g., telomere length and DNA methylation (DNAm). Telomere shortening associates with biological age in newborns, and DNA methylation at specific CpG sites can be used to calculate "epigenetic clocks". OBJECTIVE: The aim of this study was to examine the associations of prenatal lead exposures with telomere length and DNA-methylation-based predictors of age in cord blood. DESIGN: The study included 507 mother-child pairs from the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study, a birth cohort in Mexico City. Maternal blood (second trimester, third trimester and at delivery) and bone lead levels (one month postpartum) were measured using inductively coupled plasma-mass spectrometry and X-ray fluorescence, respectively. Cord blood leukocyte telomere length was measured using quantitative PCR and apparent age by DNA methylation biomarkers, i.e., Horvath's DNA methylation age and the Knight's predictor of gestational age. RESULTS: Average maternal age was 28.5 ± 5.5 years, and 51.5% reported low socioeconomic status. Children's mean telomere length was 1.2 ± 1.3 relative units, and mean DNA methylation ages using the Horvath's and Knight's clocks were -2.6 ± 0.1 years and 37.9 ± 1.4 weeks (mean ± SD), respectively. No significant associations were found between maternal blood and bone lead concentrations with telomere length and DNAm age in newborns. CONCLUSION: We found no associations of prenatal lead exposure with telomere length and DNA methylation age biomarkers.

Pesticide Exposure Modifies DNA Methylation of Coding Region of WRAP53α, an Antisense Sequence of p53, in a Mexican Population.

The influence of pesticide exposure in alteration of DNA methylation patterns of specific genes is still limited, specifically in natural antisense transcripts (NAT), such as the WRAP53α gene. The aim of this study was to determine the methylation of the WRAP53α gene in mestizo and indigenous populations as well as its relationship with internal (age, sex, and body mass index) and external factors (pesticide exposure and micronutrient intake). A cross-sectional study was conducted including 91 mestizo individuals without occupational exposure to pesticides, 164 mestizo urban sprayers and 189 indigenous persons without occupational exposure to pesticides. Acute pesticide exposure was evaluated by measurement of urinary dialkylphosphate (DAP) concentration by gas chromatograph coupled to a mass spectrometer. Anthropometric characteristics, unhealthy habits, and chronic pesticide exposure were assessed using a structured questionnaire. The frequency of macro- and micronutrient intake was determined using SNUT software. DNA methylation of the WRAP53α gene was determined by pyrosequencing of bisulfite-modified DNA. The mestizo sprayers group had the higher values of %5mC. In addition, this group had the most DAP urinary concentration with respect to the indigenous and reference groups. Bivariate analysis showed an association between %5mC of the WRAP53α gene with micronutrient intake and pesticide exposure in mestizo sprayers, whereas changes in %5mC of the WRAP53α gene was associated with body mass index in the indigenous group. These data suggest that the %5mC of the WRAP53α gene can be influenced by pesticide exposure and ethnicity in the study population, and changes in the WRAP53α gene might cause an important cell process disturbance.