Pregnancy conditions like maternal pre-pregnancy obesity and gestational diabetes (GDM) have been linked with the development of placenta, a critical organ required for maternal-fetal interface during gestation, and can lead to adverse health outcomes in both mother and fetus. However, the molecular signatures associated with these conditions are not fully understood. Epigenetic clocks, which are based upon DNA methylation of age-related CpGs, are thought to better reflect biological age compared to chronological age and have been used in different tissues as potential biomarkers. In the present study, we hypothesized that altered placental epigenetic gestational aging is associated with pre-pregnancy obesity and GDM. We explored these relationships by leveraging data from three diverse cohorts in the Environmental influences on Child Health Outcomes (ECHO) program (overall N=830) . First, we investigated associations between maternal pre-pregnancy obesity and GDM and estimated placental epigenetic gestational age acceleration (eGAA) . Next, we examined associations between these two conditions and methylation of each CpG site within the robust placental clock (558 CpGs) . Significant associations were not observed between pre-pregnancy obesity and GDM and eGAA. Interestingly, pre-pregnancy obesity was associated with methylation levels at 28 placental clock CpGs (q<0.1) . These sites were annotated to 17 unique genes that enrich processes like circadian entrainment and cellular response to glucagon stimulus (GNAS, GNG2) . Additionally, GDM was associated with methylation levels at 22 CpGs that mapped to 14 genes related to apoptosis (TNFRSF10B, TRADD) and neurological development (CACNA1G, ATXN1) . Overall, findings suggest that maternal pre-pregnancy obesity and GDM are associated with CpG methylation of the placental epigenetic clock, revealing potential markers vital for healthy pregnancy and fetal development.


K.Huff: None. C.Marsit: None. S.Niemiec: None. H.Volk: None. T.M.O'shea: None. R.Fry: None. K.Roell: None. C.Bulka: None. K.E.Boyle: None. C.Breton: None. A.Burt: None. D.Dabelea: None. L.Kahn: None. M.R.Karagas: None.


National Institutes of Health (UH3OD023348)

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