What question did this study set out to answer?

The study aims to understand how high glucose levels affect different cells at the feto-maternal interface and their role in pregnancy.

April 18, 2026

High glucose exposure induces differential pathophysiologic changes in feto-maternal interface cells

Key Points

The study aims to understand how high glucose levels affect different cells at the feto-maternal interface and their role in pregnancy.
Human placental trophoblasts, fetal membranes, and amnion epithelial cells were exposed to 50 mM glucose.
Cell markers were measured using immunocytochemistry (ICC) and flow cytometry.
Cytotoxicity was assessed through LDH assay, and signaling pathways were analyzed by western blot.
GLUT expression was evaluated using RT-qPCR.
Cytokines and oxidative stress levels were measured using ELISA and glutathione assays.
Placental trophoblasts showed increased activation of mTOR and p38 MAPK pathways.
Fetal membranes demonstrated an inflammatory response with NF-κB activation and increased IL-8 production.
Decidua exhibited reduced GLUT expression but minimal activation of stress signaling.
Amnion epithelial cells downregulated GLUTs and maintained redox balance through increased GSH production.

Abstract

Gestational diabetes mellitus (GDM), a hyperglycemic condition during pregnancy, increases the risk of macrosomia and preterm birth (PTB). Nutrient-sensing pathways, particularly mTOR in placental trophoblasts (PTC), promote fetal overgrowth. NF-κB, oxidative stress, and p38 MAPK pathways in fetal membranes and decidua (DEC) contribute to PTB. However, the impact of hyperglycemia on these compartments remain unclear. We hypothesized that hyperglycemia differentially affects these maternal, placental, and fetal membrane interface cells, inducing macrosomia-associated pathways and perturbing homeostasis through different pathophysiologic signals. Human PTC, DEC, and amnion epithelial (AEC) cells were exposed to 50 mM glucose for up to 48 hr. Cell markers (ICC), cell cycle (flow cytometry), cytotoxicity (LDH assay), GLUT expression (RT-qPCR), signaling (mTOR, p38 MAPK, NF-κB by western blot), cytokines (ELISA), and oxidative stress (glutathione assay) were measured. PTC showed increased mTOR and p38 MAPK activation (p≤0.05), reduced GSH levels and GSH/GSSG balance (p≤0.05), but maintained GLUT expression. DEC reduced GLUT1/3 expression (p≤0.01, p≤0.05) with minimal stress and nutrient signaling. Neither cell type showed NF-κB activation. AEC downregulated GLUT1/3/11 (p≤0.05-0.0001), activated NF-κB (p≤0.01), produced IL-8 (p≤0.01), increased GSH production (p≤0.05), but maintained mTOR signaling and GSH/GSSG balance. Hyperglycemia induces compartment-specific adaptations across the feto-maternal interface. Placental trophoblasts preserve nutrient transport capacity and nutrient-signaling despite redox imbalanc.e Fetal membranes exhibit inflammatory response, while decidua reduce transport capacity with minimal stress activation. Together, these findings suggest that hyperglycemia may preferentially support fetal growth through trophoblasts while sensitizing decidua and membrane to secondary stressors.

Bookmark

Cite This Study

Perias et al. (Wed,) studied this question.

synapsesocial.com/papers/69e3205140886becb653f754 https://doi.org/https://doi.org/10.1530/joe-25-0411

Bookmark