Abstract
Few studies have investigated the correlation between maternal polyunsaturated fatty acids (PUFAs) and telomeres in offspring, and the underlying influential mechanisms. In this study, we assessed the associations of maternal PUFAs with telomere length (TL) and DNA methylation of the telomerase reverse transcriptase (TERT) promoter in the cord blood and the placenta. A total of 274 pregnant women and their newborn babies were enrolled in this study. Maternal blood before delivery, the cord blood, and the placenta at birth were collected. Fatty acids in maternal erythrocytes and cord blood cells were measured by gas chromatography (GC). TL in the cord blood and the placenta was determined using real-time quantitative PCR (qPCR) by calculating the product ratio of telomeric DNA to the single-copy gene β-globin. The TERT promoter methylation was analyzed by DNA bisulfite sequencing. The associations of maternal fatty acids with TL were analyzed by univariate and multivariate regression. We found that low concentrations of docosapentaenoci acid (DPA, C22: 5n-3) and total n-3 PUFAs, adrenic acid (ADA, C22: 4n-6), and osbond acid (OA, C22: 5n-6) and high concentrations of linoleic acid (LA, C18: 2n-6) in maternal erythrocytes were associated with the shortened TL in cord blood cells (estimated difference in univariate analysis −0.36 to −0.46 for extreme quintile compared with middle quintile), and that low concentrations of cord blood docosahexaenoic acid (DHA, C22: 6n-3) were related to the shortened TL in cord blood cells. Differently, high concentrations of α-linolenic acid (LNA, C18: 3n-3), eicosatrienoic acid (EA, C20: 3n-3), DHA, and γ-linoleic acid (GLA, C18:3n-6) in maternal erythrocytes were associated with the shortened TL in the placenta (estimated difference in univariate analysis −0.36 to −0.45 for higher quintiles compared with the middle quintile). Further examination demonstrated that the concentrations of DHA and total n-3 PUFAs in maternal erythrocytes had positive associations with DNA methylation of the TERT promoter in the cord blood instead of the placenta. These data suggest that maternal PUFAs are closely correlated to infant TL and the TERT promoter methylation, which are differently affected by maternal n-3 PUFAs between the cord blood and the placenta. Therefore, keeping higher levels of maternal n-3 PUFAs during pregnancy may help to maintain TL in the offspring, which is beneficial to long-term health.
Highlights
The developmental origins of health and disease (DoHaD) hypothesis posit that nutritional factors and environmental stimuli in the early life stage have important long-term consequences for subsequent health and susceptibility of chronic diseases, in particular, diabetes, obesity, and cardiovascular disease [1, 2]
After the adjustment for relevant variables, lower concentrations of maternal erythrocyte γ-linoleic acid (GLA), adrenic acid (ADA), osbond acid (OA), docosapentaenoci acid (DPA), and total n-3 polyunsaturated fatty acids (PUFAs), and higher concentrations of linoleic acid (LA), total n-6 PUFAs, and higher n-6/n-3 PUFA ratio were associated with the shortened Telomere length (TL) in cord blood cells
Low concentrations of maternal n-3 PUFAs and some of n-6 PUFAs (GLA, ADA, and OA), and high concentrations of LA and high n-6/n-3 PUFA ratio were associated with the shortened TL in cord blood cells; low concentrations of cord blood docosahexaenoic acid (DHA) were related to the shortened cord blood TL
Summary
The developmental origins of health and disease (DoHaD) hypothesis posit that nutritional factors and environmental stimuli in the early life stage have important long-term consequences for subsequent health and susceptibility of chronic diseases, in particular, diabetes, obesity, and cardiovascular disease [1, 2]. Two developmental pathways explain the DoHaD concept—the adaptive programming resulting from a mismatch between in utero and postnatal environments, and the direct exposure of the fetus to environmental factors, causing increased disease risk later in life [3, 4]. The specialized DNA-protein structures located at the end of eukaryotic chromosomes, are composed of noncoding double-stranded repeats of guanine-rich tandem DNA sequences and shelterin protein structures [8], which function to maintain chromosome stability and prevent the loss of genomic information caused by the semiconservative replication of DNA during cell division [9]. Telomere length (TL) is maintained by the active telomerase consisting of a single long noncoding telomerase RNA (TER), telomerase reverse transcriptase (TERT), and other proteins, which prevent telomere shortening during DNA duplication by adding telomeric repeat DNA to chromosome ends [10].
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