Placental Health in Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) profoundly influences the structure, function and molecular biology of the placenta, the critical interface between mother and fetus. Morphologically, GDM is associated with delayed villous maturation, characterised by reduced formation of vasculo-syncytial membranes and increased syncytial knots, together with evidence of stroma oedema and perivillous fibrin deposition. Ultrastructural studies reveal thickening of the trophoblast basal membrane, loss of microvillous density and mitochondrial and endoplasmic reticulum alterations within syncytiotrophoblasts, suggesting impaired barrier and transport properties. Functionally, GDM placentas show hypervascularisation driven by imbalances in angiogenic regulators such as vascular endothelial growth factors and their receptors, and nutrient transporters may be altered, affecting fetal growth trajectories. At a molecular level, dysregulation of signalling pathways—principally the mechanistic target of rapamycin (mTOR) axis modulated by Akt and AMPK kinases—alters trophoblast proliferation and nutrient sensing. Emerging work on non-coding RNAs, particularly microRNAs, unveils additional layers of gene regulation that may underpin long-term metabolic programming in offspring. Clinically, these insights hold promise for novel biomarkers to assess placental function in GDM and for targeted interventions to mitigate adverse perinatal outcomes and the lifelong risk of metabolic disease.

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Placental Health in Gestational Diabetes Mellitus publication trend

The graph below shows the total number of articles in placental health in gestational diabetes mellitus across all publications each year (not limited to Nature Index journals).

Technical terms

MicroRNA (miRNA): small non-coding RNA molecules that regulate gene expression post-transcriptionally, influencing placental cell proliferation and differentiation.

Villous maturation: developmental process by which placental villi form mature vasculo-syncytial membranes to optimise maternal–fetal exchange.

Vasculo-syncytial membrane: specialised thin barrier in terminal villi where trophoblasts and fetal capillaries are closely apposed for efficient gas and nutrient transfer.

Mechanistic target of rapamycin (mTOR): central kinase controlling cell growth and nutrient sensing in trophoblasts, modulated by upstream kinases Akt and AMPK.

Human equilibrative nucleoside transporter 1 (hENT1): membrane protein facilitating adenosine uptake in placental endothelial cells, critical for vascular adaptation.

References

1. Histopathological placental lesions in mild gestational hyperglycemic and diabetic women. Diabetology & Metabolic Syndrome (2011).
2. Ultrastructure of Placenta of Gravidas with Gestational Diabetes Mellitus. Obstetrics and Gynecology International (2015).
3. Vascular endothelial growth factor and its receptors regulation in gestational diabetes mellitus and eclampsia. Journal of Translational Medicine (2022).
4. The role of microRNAs in pregnancies complicated by maternal diabetes. Clinical Science (2024).
5. Gestational Diabetes—Placental Expression of Human Equilibrative Nucleoside Transporter 1 (hENT1): Is Delayed Villous Maturation an Adaptive Pattern?. Diagnostics (2023).
6. Differential Changes in Akt and AMPK Phosphorylation Regulating mTOR Activity in the Placentas of Pregnancies Complicated by Fetal Growth Restriction and Gestational Diabetes Mellitus With Large-For-Gestational Age Infants. Frontiers in Medicine (2021).