Advanced glycation end-products change placental barrier function and tight junction in rats with gestational diabetes mellitus via the receptor for advanced glycation end products/nuclear factor-κB pathway

The placenta plays an important role in nutrient transport to maintain the growth and development of the embryo.Gestational diabetes mellitus(GDM),the most common complication during pregnancy,highly affects placental function in late gestation.Advanced glycation end-products(AGEs),a complex and heterogeneous group of compounds engaged by the receptor for AGEs(RAGE),are closely associated with diabetes-related complications.In this study,AGEs induced a decrease in the expression of tight junction(TJ)proteins in BeWo cells and increased the paracellular permeability of trophoblast cells by regulating RAGE/NF-κB.Sprague-Dawley(SD)rats injected with 100 mg/kg AGEs-rat serum albumin(RSA)via the tail vein from embryo day 2 were set as the placental barrier dysfunction model group(n=10).The effect of AGEs on placental permeability was determined using the Evans-Blue dye extravasation method.The ultrastructure of the placenta samples was observed by transmission electron microscopy.The effects of AGEs on the placenta were confirmed by treating rats with RAGE antagonist FPS-ZM1 and soluble forms of RAGE(sRAGE).AGEs treatment increased placental permeability and disrupted the tight junctions in pregnant rat placenta,but has no effect on blood glucose.The expression of TJ-related proteins,including ZO-1,Occludin,and Claudin 5,were downregulated after AGEs treatment.Further,AGEs treatment increased the expression of RAGE and nuclear factor-κB in the placenta of rats and upregulated the levels of vascular endothelial growth factor.The effects of AGEs on the placenta were blocked by RAGE antagonist FPS-ZM1 and sRAGE.This study demonstrates the mechanism underlying AGEs-induced disturbance in placental function in pregnant rats and highlights the potential of AGEs in the treatment of GDM.

Pregnancy complications effect on the nickel content in maternal blood,placenta blood and umbilical cord blood during pregnancy

BACKGROUND Nickel(Ni)may accumulate in the human body and has biological toxicity and carcinogenicity.Ni has an extensive impact on the health of pregnant women and fetuses during gestation.AIM To evaluate Ni exposure in pregnant women in Kunming,Yunnan Province,China;to describe the distribution of Ni in the maternal-fetal system and placental barrier function;and to investigate the effect of Ni exposure on fetal health in mothers with pregnancy complications.METHODS Seventy-two pregnant women were selected using a case-control design.The women were divided into two groups:The control group(no disease;n=29)and the disease group[gestational diabetes(GDM),hypertensive disorder complicating pregnancy(HDCP),or both;n=43].The pregnant women in the disease group were further divided as follows:14 cases with GDM(GDM group),13 cases with HDCP(HDCP group)and 16 cases with both GDM and HDCP(disease combination group).Basic information on the pregnant women was collected by questionnaire survey.Maternal blood,placenta blood and cord blood were collected immediately after delivery.The Ni content in paired samples was determined using inductively coupled plasma mass spectrometry.RESULTS Compared to the control group,age was higher and body mass index was greater in pregnant women in the disease groups(28.14±2.54 vs 28.42±13.89,P<0.05;25.90±3.86 vs 31.49±5.30,P<0.05).The birth weights of newborns in the HDCP group and the control group were significantly different(2.52±0.74 vs 3.18±0.41,P<0.05).The content of Ni in umbilical cord blood in the entire disease group was higher than that in the control group(0.10±0.16 vs 0.05±0.07,P<0.05).CONCLUSION In the maternal-fetal system of women with pregnancy complications,the barrier effect of the placenta against Ni is weakened,thus affecting healthy growth of the fetus in the uterus.