Deyssenroth, M. A. | bioRxiv Science

bioRxiv2019

Placental DNA methylation signatures of maternal smoking during pregnancy and potential impacts on fetal growth

Maternal smoking during pregnancy (MSDP) contributes to poor birth outcomes, in part through disrupted placental functions, which may be reflected in the placental epigenome. We meta-analyzed the associations between MSDP and placental DNA methylation (DNAm) and between DNAm and birth outcomes within the Pregnancy And Childhood Epigenetics (PACE) consortium (7 studies, N=1700, 344 with any MSDP). We identified 1224 CpGs that were associated with MSDP, of which 341 associated with birth outcomes and 141 associated with gene expression. Only 6 of these CpGs were consistent with the findings from a prior meta-analysis of cord blood DNAm, demonstrating substantial tissue-specific responses to MSDP. The placental MSDP associated CpGs were enriched for growth-factor signaling, hormone activity, inflammation, and vascularization, which play important roles in placental function. We demonstrate links between placental DNAm, MSDP and poor birth outcomes, which may better inform the mechanisms through which MSDP impacts placental function and fetal growth.

genomics↗

bioRxiv2018

Epigenome-wide association study of placental DNA methylation and maternal exposure to night shift work in the Rhode Island Child Health Study

ObjectivesCircadian disruption from environmental and occupational exposures can potentially impact health, including offspring health, through epigenetic alterations. Night shift workers experience circadian disruption, but little is known about how this exposure could influence the epigenome of the placenta, which is situated at the maternal-fetal interface. To investigate whether night shift work is associated with variations in DNA methylation patterns of placental tissue, we conducted an epigenome-wide association study (EWAS) of night shift work.\n\nMethodsCpG specific methylation genome-wide of placental tissue (measured with the Illumina 450K array) from participants (n=237) in the Rhode Island Child Health Study (RICHS) who did (n=53) and did not (n=184) report working the night shift was compared using robust linear modeling, adjusting for maternal age, pre-pregnancy smoking, infant sex, maternal adversity, and putative cell mixture.\n\nResultsNight shift work was associated with differential methylation in placental tissue, including CpG sites in the genes NAV1, SMPD1, TAPBP, CLEC16A, DIP2C, FAM172A, and PLEKHG6 (Bonferroni-adjusted p<0.05). CpG sites within NAV1, MXRA8, GABRG1, PRDM16, WNT5A, and FOXG1 exhibited the most hypomethylation, while CpG sites within TDO2, ADAMTSL3, DLX2, and SERPINA1 exhibited the most hypermethylation (BH q<0.10). PER1 was the only core circadian gene demonstrating differential methylation. Functional analysis indicated GO-terms associated with cell-cell adhesion.\n\nConclusionsNight shift work was associated with differential methylation of the placenta, which may have implications for fetal health and development. Additionally, neuron navigator 1 (NAV1) may play a role in the development of the human circadian system.\n\nWhat is already known about this subject?Night shift work and circadian disruption may play a role in the development and progression of many diseases. However, little is known about how circadian disruption impacts human fetal health and development.\n\nWhat are the new findings?Working the night shift is associated with altered placental methylation patterns, and particularly, neuron navigator 1 (NAV1) may play a role in the development of the human circadian system.\n\nHow might this impact on policy or clinical practice in the foreseeable future?Night shift work prior to or during pregnancy may alter the placental epigenome, which has implications for fetal health. Further studies are needed to evaluate night shift work as a possible risk factor for gestational diabetes and to evaluate the impact of circadian disruption on fetal health and development.

epidemiology↗