Objectives: Preeclampsia (PE) and gestational diabetes mellitus (GDM) are two common complications in pregnancy, affecting more than 10% pregnancies worldwide. PE and GDM occur only during pregnancy and are associated with risks for both mother and child. These two pathological conditions can be often associated during pregnancy, leading to an even more dramatic clinical scenario. It has been suggested that inflammatory chemokines might be implicated in the pathophysiology of PE and GDM. Herein, we investigated expression and localization of DUFFY, key decoy receptor deputed to degradation of specific chemokines, in placentae from pregnancies complicated by both PE and GDM (PE-GDM). Moreover, we evaluated maternal serum levels of DUFFY-related chemokines, in order to understand whether DUFFY dysregulation could contribute to PE-GDM pathogenesis. Methods: Placental, umbilical cord, placental membranes biopsies and maternal serum samples were collected at third trimester from PE-GDM (n=10) and control (CTRL, n=10) pregnancies. Duffy protein levels were assessed by Western Blot, while its localization was investigated by immunohistochemistry. Serum samples were processed by Chemokine Array to detect levels of circulating chemokines. Results: DUFFY protein expression was significantly increased in PE-GDM vs CTRL placentae (p<0.05). DUFFY signal localized in the syncytiotrophoblast and membranes of both PE-GDM and CTRL samples. Moreover, DUFFY immune-reactivity was also present in the umbilical vein endothelium of PE-GDM and CTRL placentae. Chemokine Array analysis revealed an overall increase of DUFFY related chemokines in PE-GDM vs CTRL maternal serum samples. Conclusions: Herein, we demonstrated that Duffy is over-expressed in PE-GDM placentae along with elevated inflammatory chemokine levels, suggesting an abnormal DUFFY decoy receptor activity in patients with PE-GDM. Indeed, regulation of Duffy expression within PE-GDM placentae may constitute a target for therapeutic intervention in order to prevent the deleterious effects of PE-GDM on women and their offspring.
Characterization of DUFFY Decoy Receptor in Placentae from Pregnancies Complicated by both Preeclampsia and Gestational Diabetes
ROLFO, Alessandro;NUZZO, ANNA MARIA;TODROS, Tullia
2013-01-01
Abstract
Objectives: Preeclampsia (PE) and gestational diabetes mellitus (GDM) are two common complications in pregnancy, affecting more than 10% pregnancies worldwide. PE and GDM occur only during pregnancy and are associated with risks for both mother and child. These two pathological conditions can be often associated during pregnancy, leading to an even more dramatic clinical scenario. It has been suggested that inflammatory chemokines might be implicated in the pathophysiology of PE and GDM. Herein, we investigated expression and localization of DUFFY, key decoy receptor deputed to degradation of specific chemokines, in placentae from pregnancies complicated by both PE and GDM (PE-GDM). Moreover, we evaluated maternal serum levels of DUFFY-related chemokines, in order to understand whether DUFFY dysregulation could contribute to PE-GDM pathogenesis. Methods: Placental, umbilical cord, placental membranes biopsies and maternal serum samples were collected at third trimester from PE-GDM (n=10) and control (CTRL, n=10) pregnancies. Duffy protein levels were assessed by Western Blot, while its localization was investigated by immunohistochemistry. Serum samples were processed by Chemokine Array to detect levels of circulating chemokines. Results: DUFFY protein expression was significantly increased in PE-GDM vs CTRL placentae (p<0.05). DUFFY signal localized in the syncytiotrophoblast and membranes of both PE-GDM and CTRL samples. Moreover, DUFFY immune-reactivity was also present in the umbilical vein endothelium of PE-GDM and CTRL placentae. Chemokine Array analysis revealed an overall increase of DUFFY related chemokines in PE-GDM vs CTRL maternal serum samples. Conclusions: Herein, we demonstrated that Duffy is over-expressed in PE-GDM placentae along with elevated inflammatory chemokine levels, suggesting an abnormal DUFFY decoy receptor activity in patients with PE-GDM. Indeed, regulation of Duffy expression within PE-GDM placentae may constitute a target for therapeutic intervention in order to prevent the deleterious effects of PE-GDM on women and their offspring.
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