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The effect of Gestational Diabetes Mellitus on the fetal compartment
Journal of Reproductive Immunology ( IF 3.4 ) Pub Date : 2021-03-24 , DOI: 10.1016/j.jri.2021.103314
Thiago P B De Luccia 1 , Erika Ono 1 , Ramkumar Menon 2 , Alexandre Urban Borbely 3 , Rosiane Mattar 1 , Lauren Richardson 2 , Ana Lucia Mendes da Silva 3 , Rayane Martins Botelho 3 , Maria Luisa Toledo Leite Ferreira da Rocha 4 , Silvia Daher 1
Affiliation  

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.



中文翻译:

妊娠期糖尿病对胎儿隔室的影响

在指示性早产中,例如妊娠糖尿病 (GDM),对羊膜的作用知之甚少。研究羊膜炎症在 GDM 反应中的作用可能提示新的病理生理机制。我们假设 GDM 炎症介质的增加可能会削弱羊膜,使它们易于感染。从接受选择性剖宫产的 20 名 GDM 和 38 名血糖正常的受试者(对照)收集母胎血清和羊膜活检。在血清和羊膜培养上清液样品中评估细胞因子和脂肪因子。研究了来自 GDM 和对照受试者的羊膜活检:新鲜冷冻用于 Toll 样受体表达的 RNA 分析;用LPS培养检测膜通透性,炎症LPS+anti-TLR4检测机制。与对照组相比,GDM 与较高的胎儿血清瘦素 (p = 0.004) 和 IL-10 (p = 0.04) 相关。与对照组相比,来自 GDM 的羊膜外植体的 IL-6 水平较高(p = 0.019),Claudin-4 表达较低(p = 0.007),通透性增加(p = 0.046)。用 LPS 处理的 GDM 膜显示 IL-10 的表达增加(p = 0.013);IL-6 (p = 0.004) 和 TNF-α (p = 0.0005) 但不影响膜通透性。与单独的 LPS 相比,LPS 和抗 TLR4 抗体处理降低了对照 (p = 0.03) 和 GDM (p = 0.007) 中 TNF-α 的产生。GDM 中胎儿的炎症反应似乎更平衡,即使有感染性刺激也不影响膜通透性功能。轻微的胎膜炎症反应可以解释 GDM 中没有早产的原因。总结,

更新日期:2021-04-06
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