Adverse birth outcomes, such as early gestational age and low birth weight, can have lasting effects on morbidity and mortality, with impacts that persist into adulthood. Identifying the maternal factors that contribute to adverse birth outcomes in the next generation is thus a priority. Epigenetic clocks, which have emerged as powerful tools for quantifying biological aging and various dimensions of physiological dysregulation, hold promise for clarifying relationships between maternal biology and infant health, including the maternal factors or states that predict birth outcomes. Nevertheless, studies exploring the relationship between maternal epigenetic age and birth outcomes remain few. Here, we attempt to replicate a series of analyses previously reported in a US-based sample, using a larger similarly aged sample (
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Abstract n = 296) of participants of a long-running study in the Philippines. New pregnancies were identified prospectively, dried blood spot samples were collected during the third trimester, and information was obtained on gestational age at delivery and offspring weight after birth. Genome-wide DNA methylation was assessed with the Infinium EPIC array. Using a suite of 15 epigenetic clocks, we only found one significant relationship: advanced age on the epigenetic clock trained on leptin predicted a significantly earlier gestational age at delivery (β = − 0.15,p = 0.009). Of the other 29 relationships tested predicting gestational age and offspring birth weight, none were statistically significant. In this sample of Filipino women, epigenetic clocks capturing multiple dimensions of biology and health do not predict birth outcomes in offspring. -
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Abstract Background Consistent with evolutionarily theorized costs of reproduction (CoR), reproductive history in women is associated with life expectancy and susceptibility to certain cancers, autoimmune disorders and metabolic disease. Immunological changes originating during reproduction may help explain some of these relationships.
Methodology To explore the potential role of the immune system in female CoR, we characterized leukocyte composition and regulatory processes using DNA methylation (DNAm) in a cross-sectional cohort of young (20–22 years old) women differing in reproductive status.
Results Compared to nulliparity, pregnancy was characterized by differential methylation at 828 sites, 96% of which were hypomethylated and enriched for genes associated with T-cell activation, innate immunity, pre-eclampsia and neoplasia. Breastfeeding was associated with differential methylation at 1107 sites (71% hypermethylated), enriched for genes involved in metabolism, immune self-recognition and neurogenesis. There were no significant differences in DNAm between nulliparous and parous women. However, compared to nullipara, pregnant women had lower proportions of B, CD4T, CD8T and natural killer (NK) cells, and higher proportions of granulocytes and monocytes. Monocyte counts were lower and NK counts higher among breastfeeding women, and remained so among parous women.
Implications Our findings point to widespread differences in DNAm during pregnancy and lactation. These effects appear largely transient, but may accumulate with gravidity become detectable as women age. Nulliparous and parous women differed in leukocyte composition, consistent with more persistent effects of reproduction on cell type. These findings support transient (leukocyte DNAm) and persistent (cell composition) changes associated with reproduction in women, illuminating potential pathways contributing to CoR.
Lay Summary: Evolutionary theory and epidemiology support costs of reproduction (CoR) to women’s health that may involve changes in immune function. We report differences in immune cell composition and gene regulation during pregnancy and breastfeeding. While many of these differences appear transient, immune cell composition may remain, suggesting mechanisms for female CoR.
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Using DNA methylation profiles (
n = 15,456) from 348 mammalian species, we constructed phyloepigenetic trees that bear marked similarities to traditional phylogenetic ones. Using unsupervised clustering across all samples, we identified 55 distinct cytosine modules, of which 30 are related to traits such as maximum life span, adult weight, age, sex, and human mortality risk. Maximum life span is associated with methylation levels inHOXL subclass homeobox genes and developmental processes and is potentially regulated by pluripotency transcription factors. The methylation state of some modules responds to perturbations such as caloric restriction, ablation of growth hormone receptors, consumption of high-fat diets, and expression of Yamanaka factors. This study reveals an intertwined evolution of the genome and epigenome that mediates the biological characteristics and traits of different mammalian species.Free, publicly-accessible full text available August 11, 2024 -
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Abstract Objectives Socioeconomic status (SES) is a powerful determinant of health, but the underlying biological mechanisms are poorly understood. This study investigates whether levels of DNA methylation at CpG sites across the genome are associated with SES in a cohort of young adults in the Philippines.
Methods DNA methylation was assayed with the Illumina HumanMethylation450 Bead Chip, in leukocytes from 489 participants in the Cebu Longitudinal Health and Nutrition Survey (mean age = 20.9 years). SES was measured in infancy/childhood and adulthood, and was based on composite measures of income, assets, and education. Genome‐wide analysis of variable probes identified CpG sites significantly associated with SES after adjustment for multiple comparisons. Functional enrichment analysis was used to identify biological pathways associated with these sites.
Results A total of 2,546 CpG sites, across 1,537 annotated genes, were differentially methylated in association with SES. In comparison with high SES, low SES was associated with increased methylation at 1,777 sites, and decreased methylation at 769 sites. Functional enrichment analysis identified over‐representation of biological pathways related to immune function, skeletal development, and development of the nervous system.
Conclusions Socioeconomic status predicts DNA methylation at a large number of CpG sites across the genome. The scope of these associations is commensurate with the wide range of biological systems and health outcomes that are shaped by SES, and these findings suggest that DNA methylation may play an important role.
