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Gestational diabetes mellitus impairs metabolic homeostasis and cardiac development of offsprings by epigenetic regulation of H3K27 methylation to key pro-fibrosis transcription factor MEOX1

ABSTRACT: As one of the most perinatal period metabolic disorders, gestational diabetes mellitus (GDM) has negative influence to the metabolic health as well as organ development of offsprings. The underlying mechanism(s) is not fully revealed.

ORGANISM(S): Mus musculus

PROVIDER: GSE261295 | GEO | 2026/03/06

REPOSITORIES: GEO

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Project description:Objectives To perceive the temporal features of breast milk proteome between women with gestational diabetes mellitus (GDM) and healthy controls across various lactation periods, as well as to explore the potential impacts of these differences on the growth of offspring. Methods The study cohort included twenty mothers with GDM and twenty healthy mothers. Human milk samples were obtained at four distinct time points: colostrum (4-6 days postpartum), transitional milk (12-14 days postpartum), early mature milk (42 days postpartum) and mature milk (4 months postpartum). Shotgun proteomics with label free quantification was applied to analyze the milk proteome. Gene Ontology (GO) enrichment analysis, alongside other bioinfomatic tools were conducted to elucidate the function of differentially expressed proteins. Subsequently, a random forest model was utilized to discern proteins that could reliably differentiate milk samples from mothers with gestational diabetes mellitus (GDM) from those of healthy counterparts. Furthermore, correlative analysis was employed to investigate the association between these proteins and the anthropometric indices of infants. Results Principal coordinate analysis (PCoA) revealed distinct separations in the milk proteome of GDM and healthy mothers during the initial lactation stages, with these differences diminishing over time. The up-regulated proteins in GDM were predominantly associated with the innate immune system, complement and coagulation cascades, cellular secretion, enzymatic and binding activity, and platelet activation. Six proteins were identified as effective markers for distinguishing milk samples from the two groups, with an average area under the curve (AUC) value of 0.91. Twenty-eight proteins exhibited consistent changes between GDM and healthy groups across at least two lactation stages, many of which were significantly correlated to the anthropometric indices of the offsprings. Conclusions GDM significantly influences the milk proteome, with the extent of alteration diminishing as lactation progresses into the mature milk phase.

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Gestational diabetes mellitus impairs metabolic homeostasis and cardiac development of offsprings by epigenetic regulation of H3K27 methylation to key pro-fibrosis transcription factor MEOX1

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