Decoding the molecular landscape of the placenta in maternal diabetes: a systematic review of high-throughput data
File(s)
Published version
Author(s)
Fakonti, Georgia
Byford, Abigail R
Scott, Eleanor M
Holder, Beth
Forbes, Karen
Type
Journal Article
Abstract
Diabetes in pregnancy is associated with significant short- and long-term complications for mothers and offspring, many of which are thought to result from altered placental development and function. Although studies have demonstrated molecular changes in the placenta in this context, the precise mechanisms remain unclear. High-throughput transcriptomic and proteomic approaches provide powerful tools to systematically identify disease-associated pathways, yet no systematic synthesis of this literature has been undertaken. We conducted a systematic review of omics studies examining placental molecular changes in pregnancies complicated by diabetes compared with uncomplicated pregnancies. Fifty-six studies were eligible for inclusion, the majority of which focused on gestational diabetes mellitus (GDM; n = 52). Of these, 42 reported changes in RNA (n = 30) or protein (n = 12) abundance, with eight proteins and 189 RNA species consistently altered in at least two studies. Functional enrichment analysis revealed dysregulation of immune, vascular, and developmental pathways. Notably, 98 molecules were altered at both RNA and protein levels, 47 with consistent directionality across studies, suggesting robust disruption of core biological pathways. Comparisons across diabetes types showed partial overlap of differentially expressed transcripts between GDM and type 1 diabetes (16 genes) and GDM and type 2 diabetes (34 genes), although no universal markers were identified. These findings highlight shared molecular signatures in GDM, provide novel insights into pathways linking maternal diabetes to placental dysfunction and adverse outcomes, and emphasise the need for further studies on type 1 and type 2 diabetes. These pathways may represent potential therapeutic targets to mitigate intergenerational cardiometabolic risk.
Date Issued
2026-04-01
Date Acceptance
2026-03-13
Citation
Journal of Molecular Endocrinology, 2026, 76 (3)
ISSN
0952-5041
Publisher
Bioscientifica
Journal / Book Title
Journal of Molecular Endocrinology
Volume
76
Issue
3
Copyright Statement
© 2026 the author(s) Published by Bioscientifica Ltd. This work is licensed under a Creative Commons Attribution 4.0 International License.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/41838464
PII: e250131
Subjects
RNA sequencing
functional enrichment analysis
gestational diabetes mellitus
high-throughput
omics
placenta
proteomics
type 1 diabetes mellitus
type 2 diabetes mellitus
Female
Pregnancy
Placenta
Humans
Diabetes, Gestational
Proteomics
Gene Expression Profiling
Diabetes Mellitus, Type 1
Transcriptome
Diabetes Mellitus, Type 2
Publication Status
Published
Coverage Spatial
England
Article Number
e250131
Date Publish Online
2026-03-16