Associations between maternal plasma zinc concentrations in late pregnancy and LINE-1 and Alu methylation loci in the young adult offspring

Abstract

Background In animal models, prenatal zinc deficiency induced epigenetic changes in the fetus, but data in humans are lacking. We aimed to examine associations between maternal zinc levels during pregnancy and DNA methylation in LINE-1 and Alu repetitive sequences in young adult offspring, as well as anthropometry and cardiometabolic parameters. Methods Participants were 74 pregnant women from the Chiang Mai Low Birth Weight cohort, and their offspring followed up at 20 years of age. Maternal plasma zinc concentrations were measured at approximately 36 weeks of gestation. DNA methylation levels in LINE-1 and Alu repetitive sequences were measured in the offspring, as well as anthropometry and cardiometabolic parameters (lipid profile, blood pressure, and glucose metabolism). Results Over half of mothers (39/74; 53%) were zinc deficient (<50 μg/dL) during their third trimester of pregnancy. Maternal zinc concentrations during pregnancy were associated with LINE-1 DNA methylation levels in adult offspring. Specifically, lower prenatal zinc concentrations were associated with: 1) lower levels of total LINE-1 methylation; 2) lower levels of LINE-1 hypermethylation loci; and 3) higher levels of LINE-1 partial methylation loci. Prenatal zinc concentrations were not associated with Alu methylation levels, nor with any anthropometric or cardiometabolic parameters in adult offspring. However, we observed associations between Alu and LINE-1 methylation patterns and cardiometabolic outcomes in offspring, namely total cholesterol levels and diastolic blood pressure, respectively. Conclusions Lower maternal zinc concentrations late in gestation were associated with changes in DNA methylation in later life. Thus, zinc deficiency during pregnancy may induce alterations in total LINE-1 methylation and LINE-1 hypermethylation loci. These results suggest a possible epigenetic link between zinc deficiency during pregnancy and long-term outcomes in the offspring.