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

Area of Science:

• Reproductive biology and endocrinology
• Cellular and molecular pathophysiology
• Pregnancy complications

Background:

• Gestational diabetes mellitus (GDM) is linked to macrosomia and preterm birth (PTB).
• mTOR signaling in placental trophoblasts (PTC) promotes fetal overgrowth.
• NF-κB, oxidative stress, and p38 MAPK pathways in fetal membranes and decidua (DEC) are implicated in PTB.

Purpose of the Study:

• To investigate the differential effects of hyperglycemia on maternal-fetal interface cells.
• To elucidate the molecular mechanisms underlying GDM-associated complications like macrosomia and PTB.

Main Methods:

• Human placental trophoblast (PTC), decidua (DEC), and amnion epithelial (AEC) cells were exposed to high glucose (50 mM).
• Assessed cell markers, cell cycle, cytotoxicity, glucose transporter (GLUT) expression, signaling pathways (mTOR, p38 MAPK, NF-κB), cytokines, and oxidative stress (glutathione).

Main Results:

• PTC showed increased mTOR and p38 MAPK activation, reduced glutathione (GSH) levels, but maintained GLUT expression.
• DEC exhibited reduced GLUT1/3 expression with minimal stress and signaling activation.
• AEC downregulated GLUTs, activated NF-κB, produced IL-8, and increased GSH production, while maintaining mTOR signaling.

Conclusions:

• Hyperglycemia induces distinct adaptations in placental, decidual, and fetal membrane cells.
• Placental trophoblasts maintain nutrient transport and signaling despite redox imbalance.
• Fetal membranes mount an inflammatory response, and decidua reduce transport capacity, suggesting a complex interplay in GDM pathophysiology.