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Cited by 4Gestational Diabetes Research and ManagementPregnancy and preeclampsia studiesBirth, Development, and Health

Decoding the molecular landscape of the placenta in maternal diabetes: A systematic review of high-throughput data

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Fakonti, Georgia, Byford, Abigail R, Scott, Eleanor M, Holder, Beth, Forbes, Karen·2026·Journal of Molecular Endocrinology
DOI 10.1530/jme-25-0131PMC PMC13097123
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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.

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Authors
Fakonti, G., Byford, A. R., Scott, E. M., Holder, B., & Forbes, K.
Affiliations
  • 1
  • 2
  • 3
Corresponding author
  • Fakonti, Georgia
  • Forbes, Karen
ORCID
Venue
Journal of Molecular Endocrinology
Publisher
Bioscientifica
Published
2026-03-16
Volume
76
Issue
3
ISSN
  • 0952-5041 (ISSN-L)
  • 1479-6813
DOI
10.1530/jme-25-0131
PMC
PMC13097123
OpenAlex
W7136292628
Cited by
4
References
0
Citations by year
2026: 4
FWCI
6.62
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Molecular Endocrinology (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion, cc-by)
  • Spiral (Imperial College London) (submittedVersion, cc-by)
Funders
  • UK Research and Innovation
  • University of Leeds
  • Medical Research Council (MR/R023166/1, MR/Y003659/1)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Keywords
placenta, maternal diabetes, gestational diabetes mellitus, type 1 diabetes in pregnancy, type 2 diabetes in pregnancy, placental transcriptome, placental proteome, placental insufficiency, differentially expressed genes
MeSH terms
Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Female, Humans, Placenta, Pregnancy, Diabetes, Gestational, Gene Expression Profiling, Proteomics, Transcriptome

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