The effect of Gestational Diabetes Mellitus on the fetal compartment

Thiago P.B. De Luccia, Erika Ono, Ramkumar Menon, Alexandre Urban Borbely, Rosiane Mattar, Lauren Richardson, Ana Lucia Mendes da Silva, Rayane Martins Botelho, Maria Luisa Toledo Leite Ferreira da Rocha, Silvia Daher

Research output: Contribution to journalArticlepeer-review

Abstract

In indicated preterm births such a Gestational Diabetes Mellitus (GDM), little is known about the role of the amnion membranes. Investigating the role of amnion membrane inflammation in response GDM may suggest novel pathophysiologic mechanisms. We hypothesize that increased GDM inflammatory mediators may weaken the amnion membrane predisposing them to infection. Maternal and fetal serum and amnion membrane biopsies were collected from 20 GDM and 38 normoglycemic subjects (control) who underwent elective cesarean sections. Cytokines and adipokines were evaluated in serum and amnion culture supernatant samples. Amnion membrane biopsies from GDM and control subjects were studied: fresh frozen for RNA analysis for Toll-like receptor expression; cultured with LPS to test membrane permeability, and inflammation LPS + anti-TLR4 for testing mechanism. GDM was associated with higher fetal serum leptin (p = 0.004) and IL-10 (p = 0.04) compared to controls. Amnion membrane explants from GDM had higher levels of IL-6 (p = 0.019), and lower expression of Claudin-4 (p = 0.007) and increased permeability (p = 0.046) compared to controls. GDM membranes treated with LPS showed an increased expression of IL-10 (p = 0.013); IL-6 (p = 0.004) and TNF-α (p = 0.0005) but did not affect membrane permeability. LPS and anti-TLR4 antibody treatment reduced the production of TNF-α in controls (p = 0.03) and GDM (p = 0.007) compared to LPS alone. Fetal inflammatory response seems more balanced in GDM and does not impact membrane permeability function even with an infectious stimulus. Light fetal membrane inflammatory response may explain lack of preterm labor in GDM. Concluding, benign inflammation in the membranes may not be harmful for pregnancy maintenance.

Original languageEnglish (US)
Article number103314
JournalJournal of Reproductive Immunology
Volume145
DOIs
StatePublished - Jun 2021
Externally publishedYes

Keywords

  • Adipokines
  • Amnion membrane
  • Cytokines
  • Gestational diabetes
  • Inflammation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Reproductive Medicine
  • Obstetrics and Gynecology

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