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CME Credit Offered
CME Credit Offered
Abstract Award
Abstract Award
Recording available 2/16-5/2
Recording available 2/16-5/2
AIUM Credit
AIUM Credit
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Foundation Awardee
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Abstract Award
Abstract Award
Foundation Awardee
Foundation Awardee

Poster Session 4

Category: Diabetes

Poster Session 4

(1161) Hyperglycemia and metformin differentially modulate inflammatory protein cargo in placental extracellular vesicles

Thursday, February 12, 2026
3:30 PM - 5:00 PM  
Objective:
Placental extracellular vesicles (EVs) are mediators of maternal-fetal communication. This study aimed to investigate the impact of hyperglycemia-a known inflammatory stressor, on placental EV protein content, with and without metformin treatment, using the ex-vivo human cotyledon perfusion model. We focused on key inflammatory and oxidative stress-related proteins within EVs: the inflammasome-associated Caspase-1, and the redox and inflammatory regulators thioredoxin-interacting protein (TXNIP), thioredoxin (TRX), suppressor of cytokine signaling 3 (SOCS3), and signal transducer and activator of transcription 3 (STAT3).

Study Design:
Term placentas from elective cesarean deliveries were perfused for 180 minutes with M-199 culture medium under three conditions: normoglycemia (control, n=5; glucose 100 mg/dL), hyperglycemia (n=6; glucose 400 mg/dL), and hyperglycemia with metformin (n=5; 1.0 μg/mL). Placental viability was confirmed by stable maternal/fetal flow rates, fetal artery inflow pressure, reservoir pH, and hCG secretion. EVs were isolated from maternal perfusate via differential ultracentrifugation. Western blotting confirmed trophoblastic origin (PLAP-positive) and minimal exosomal contamination (CD9/CD63-negative), and was used to quantify expression of the target proteins

Results:
EVs were successfully isolated from 16 perfusion experiments. Hyperglycemia significantly increased EV expression of Caspase-1, TRX, and SOCS3 (fold change [FC] vs. control: 1.7, 2.1, and 1.2, respectively; p< 0.05). Metformin reduced Caspase-1 and TRX expression (FC: 0.6 and 0.7, respectively) and increased expression of TXNIP, STAT3, and SOCS3.

Conclusion:
Hyperglycemia modifies the inflammatory and oxidative stress-related protein cargo of placental EVs. Metformin modulates this response, exerting both anti-inflammatory and regulatory effects on specific EV proteins. These findings suggest a complex and selective influence of metformin on placental inflammatory signaling pathways.