Placental infiltration of inflammatory markers in gestational diabetic women

Abstract

Abstract. Gestational diabetes mellitus (GDM) is pathology of glucose intolerance during pregnancy. It is influenced by maternal hyperglycemia and insulinemia through placental circulation. The study was undertaken to investigate the implication of pro-inflammatory factors in the placenta of GDM women. Thirty GDM women have delivered macrosomic babies, and 30 healthy age-matched pregnant women have delivered non macrosomic babies, were recruited in the study. The mRNAs encoding for IL-6, TLR4, TGF-β, CD68, CD14, EMR-1, CCL2, TCR-α, T-bet, GATA-3, leptin and adiponectin were quantified in placental samples by using RT-qPCR. The mRNA expression of the pro-inflammatory factors, i.e., IL-6, TLR4 and TGF-β, was increased in GDM placenta. The mRNA expression of markers of infiltration of macrophage, i.e., CD68, CD14 and EMR-1, was higher in the GDM placenta than the control placenta. The expression of mRNA of TCR-α, an indicator of T-cell infiltration, was significantly higher in the GDM placenta. Interestingly, the expression of mRNA of GATA-3, an indicator of Th2 phenotype differentiation, was unregulated in the GDM placenta. Leptin and adiponectin mRNAs were also significantly increased in the placenta of the GDM group. Our results revealed that there is an increase of inflammation in the GDM placenta which might be involved, in part, in the pathogenesis of macrosomia.

Diabetic pregnancy activates the innate immune response through TLR5 or TLR1/2 on neonatal monocyte

“…Perhaps because macrosomia, congenital malformations, hypoglycemia, and respiratory distress syndrome are well-known neonatal complications of maternal DM, the effects of maternal DM on neonatal immunity may not have garnered appropriate attention to date. However, recent findings indicate that GDM can alter the placental and neonatal immune systems (Mrizak et al, 2014;Atègbo et al, 2006), and our present study revealed that maternal DM 'hyperactivates' the neonatal innate immune response. A future clinical study likely will prove helpful in disclosing the relation between maternal DM and neonatal outcome after infection.…”

“…In one study, GDM was associated with increased expression of interleukin (IL)-6, toll-like receptor (TLR) 4, and transforming growth factor beta mRNA in the placenta (Mrizak et al, 2014). Another study showed elevated levels of T helper type 1 cytokines and low levels of IL-10 in the serum of macrosomic babies born to GDM mothers (Atègbo et al, 2006).…”

“…Recent reports indicate that gestational diabetes mellitus (GDM) can alter the placental and neonatal immune systems (Mrizak et al, 2014;Atègbo et al, 2006). In one study, GDM was associated with increased expression of interleukin (IL)-6, toll-like receptor (TLR) 4, and transforming growth factor beta mRNA in the placenta (Mrizak et al, 2014).…”

High Glucose Level Disturbs the Resveratrol-Evoked Curtailment of CX3CL1/CX3CR1 Signaling in Human Placental Circulation

“…Changes in the cytokine profile in response to hyperglycemia have been reported in placental circulation in diabetic pregnancies [11]. Since human placental vessels lack autonomic innervation, it is important to note that the humoral effects of vasoactive compounds (e.g., nitric oxide) that are produced locally by placental cells dominate the regulation of feto-placental blood flow, thus influencing vascular resistance [12].…”

“…Since human placental vessels lack autonomic innervation, it is important to note that the humoral effects of vasoactive compounds (e.g., nitric oxide) that are produced locally by placental cells dominate the regulation of feto-placental blood flow, thus influencing vascular resistance [12]. Despite some controversies, both clinical observations and histopathological studies of the human placenta have confirmed an increased incidence of inflammatory reactions in diabetes [5, 11, 13]. Considering that the most important functions of the human placenta include immunosuppression to protect the fetal “allograft” from T-cell-mediated immune aggression and infectious agents, the placental chemokine CX3CL1 may deserve special attention [14].…”