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ARTICLE

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

by YUEHUA SHI^1,#, QIUYING YAN^2,#, QIN LI³, WEI QIAN¹, DONGYAN QIAO¹, DONGDONG SUN², HONG YU^1,*

1 Department of Obstetrics and Gynaecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210023, China
2 School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
3 School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China

* Corresponding Author: Hong Yu,
# Authors contributed equally to this work

(This article belongs to the Special Issue: Reproductive Health and Embryonic Development)

BIOCELL 2023, 47(1), 165-173. https://doi.org/10.32604/biocell.2022.023043

Received 07 April 2022; Accepted 16 June 2022; Issue published 26 September 2022

Abstract

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 EvansBlue 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.

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