Carmela Santangelo1, Tiziana Filardi2, Giuseppina Perrone3, Marianna Mariani3, Emanuela Mari4, Beatrice Scazzocchio5, Roberta Masella5, Roberto Brunelli3, Andrea Lenzi2, Alessandra Zicari4, Susanna Morano2. 1. Center for Gender-Specific Medicine, Gender Specific Prevention and Health Unit, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy. carmela.santangelo@iss.it. 2. Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza University of Rome, Rome, Italy. 3. Department of Gynecology Obstetrics and Urology, "Sapienza" University of Rome, Rome, Italy. 4. Department of Experimental Medicine, 2nd Section of Cell Pathology, Sapienza University of Rome, Viale Regina Elena 324, Rome, Italy. 5. Center for Gender-Specific Medicine, Gender Specific Prevention and Health Unit, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161, Rome, Italy.
Abstract
AIMS: Gestational diabetes mellitus (GDM) is defined as glucose intolerance that is first diagnosed during pregnancy. Maternal adipose tissue and fetal membranes secrete various molecules that are relevant players in the pathogenesis of GDM. This pilot study aimed to examine whether the expression of the high mobility group box 1 protein (HMGB1) and its receptor for advanced glycation end products (RAGE), and the vasoactive intestinal peptide (VIP) and its receptors (VPAC-1,-2) were modified in pregnant women with GDM. METHODS: Fetal membranes (FMs), omental adipose tissue (VAT) explants, and serum samples were obtained from 12 women with GDM and 12 with normal glucose tolerance (NGT) at delivery. The expression of HMGB1, RAGE and VIP, VPAC-1,-2 was detected by Western Blotting in explants; circulating levels and "in vitro" release of HMGB1 and VIP were measured by ELISA tests. RESULTS: HMGB1 tissue expression was higher in FMs obtained from GDM women (p = 0.02) than in FMs from NGT women. VPAC2 (p = 0.03) and RAGE (p = 0.03) tissue expressions were significantly increased in VAT from GDM subjects. Only FMs of NGT released detectable levels of HMGB1, which was not observed in samples obtained from GDM. VAT of GDM released lower levels of VIP (p = 0.05) than NGT samples. CONCLUSIONS: This study indicates that a fine tuned regulation exists between FMs and VAT throughout pregnancy to maintain immune metabolic homeostasis. In GDM a balance between inflammatory and anti-inflammatory mediators has been observed. Further studies are needed to establish their exact role on fetal and maternal outcomes in GDM.
AIMS: Gestational diabetes mellitus (GDM) is defined as glucose intolerance that is first diagnosed during pregnancy. Maternal adipose tissue and fetal membranes secrete various molecules that are relevant players in the pathogenesis of GDM. This pilot study aimed to examine whether the expression of the high mobility group box 1 protein (HMGB1) and its receptor for advanced glycation end products (RAGE), and the vasoactive intestinal peptide (VIP) and its receptors (VPAC-1,-2) were modified in pregnant women with GDM. METHODS: Fetal membranes (FMs), omental adipose tissue (VAT) explants, and serum samples were obtained from 12 women with GDM and 12 with normal glucose tolerance (NGT) at delivery. The expression of HMGB1, RAGE and VIP, VPAC-1,-2 was detected by Western Blotting in explants; circulating levels and "in vitro" release of HMGB1 and VIP were measured by ELISA tests. RESULTS:HMGB1 tissue expression was higher in FMs obtained from GDM women (p = 0.02) than in FMs from NGT women. VPAC2 (p = 0.03) and RAGE (p = 0.03) tissue expressions were significantly increased in VAT from GDM subjects. Only FMs of NGT released detectable levels of HMGB1, which was not observed in samples obtained from GDM. VAT of GDM released lower levels of VIP (p = 0.05) than NGT samples. CONCLUSIONS: This study indicates that a fine tuned regulation exists between FMs and VAT throughout pregnancy to maintain immune metabolic homeostasis. In GDM a balance between inflammatory and anti-inflammatory mediators has been observed. Further studies are needed to establish their exact role on fetal and maternal outcomes in GDM.
Entities:
Keywords:
Fetal membranes; Gestational diabetes mellitus; High mobility group box 1 protein; Inflammation; Vasoactive intestinal peptide; Visceral adipose tissue
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