# Structural and Molecular Adaptations of the Placenta of Gestational Diabetes Mellitus Patients: Impact of Treatment on Vascular Endothelial Growth Factor, Vascular Endothelial Growth Factor Receptor 1, and Insulin-Like Growth Factor Expression

## TL;DR

This study examines how placental structure and growth factor expression change in gestational diabetes patients and how these changes are affected by different treatments.

## Contribution

The study identifies treatment-specific molecular adaptations in GDM placentae, particularly highlighting insulin treatment's impact on IGF and VEGF expression.

## Key findings

- Insulin-treated GDM placentae showed upregulated IGF and VEGF expression compared to other treatment groups.
- VEGF expression was significantly higher in GDM placentae, especially in syncytiotrophoblast and endothelium.
- VEGFR1 showed very strong reactivity in all GDM cases, indicating an adaptive response to hyperglycemia.

## Abstract

Background

Gestational diabetes mellitus (GDM) is a common global metabolic disorder affecting pregnant women with a rising prevalence and significant impact on the maternal-fetal outcomes. The expression of growth factors, such as vascular endothelial growth factor (VEGF) and its receptor (VEGFR1), and insulin-like growth factor (IGF), is altered in GDM, reflecting changes in placental vascularity and fetal growth regulation. Understanding these molecular alterations in GDM may help predict maternal-fetal outcomes. This study evaluates the expression of VEGF, VEGFR1, and IGF in placental tissue across different GDM treatment modalities.

Methods

This comparative cross-sectional observational study was conducted in the Department of Anatomy, Adichunchangiri Institute of Medical Sciences, BG Nagara, Mandya District, Karnataka. A total of 62 placentae were examined (31 from normoglycemic pregnancies and 31 from GDM patients). The GDM cases were further stratified into diet-controlled (n=9), oral-hypoglycemics-treated (n=11), and insulin-treated (n=11). The expression of VEGF, VEGFR1, and IGF was assessed using immunohistochemistry (IHC). Histological features, including villus morphology and vessel wall thickness, were observed with the help of hematoxylin and eosin, periodic acid-Schiff, Masson’s Trichrome, and Congo Red stains. Statistical analysis was carried out using t-tests, ANOVA, and chi-square tests.

Results

Placentae from patients with GDM, regardless of treatment modality, exhibited significantly greater positive reactivity (p<0.001) with the special stains than those of normal individuals. On IHC, IGF and VEGF expression were upregulated in placentae of insulin-treated GDM patients. IGF showed highly strong positivity in 70% of GDM cases. VEGF expression was observed in placentae of both normal and GDM cases, but the staining intensity was significantly higher in GDM placentae, especially in the syncytiotrophoblast, endothelium, and mesenchymal cells (p<0.001). VEGFR1 showed very strong positive reactivity in all GDM cases, reflecting an adaptive response to hyperglycemic conditions.

Conclusion

The structural and molecular changes observed in GDM placentae suggest that insulin treatment is associated with significant alterations in placental morphology. These findings imply that placental adaptation due to metabolic stress in GDM may vary with the intensity of treatment. The expression patterns of IGF, VEGF, and VEGFR1 may serve as potential biomarkers for monitoring placental function in relation to treatment intensity.