Open Access
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
YUEHUA SHI1,#, QIUYING YAN2,#, QIN LI3, WEI QIAN1, DONGYAN QIAO1, DONGDONG SUN2, HONG YU1,*
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.
Keywords
Cite This Article
SHI, Y., YAN, Q., LI, Q., QIAN, W., QIAO, D. et al. (2023). 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.
BIOCELL, 47(1), 165–173. https://doi.org/10.32604/biocell.2022.023043