The following is a summary of “Detrimental actions of obesity-associated advanced glycation end-products on endometrial epithelial cell proliferation are alleviated by antioxidants,” published in the July 2023 issue of Reproductive BioMedicine Online by Jennifer et al.

Advanced glycation end-products (AGE) are elevated in rotund infertile women’s uterine environment. Can therapeutics mitigate the harmful effects of AGE on endometrial epithelial cells and replicate in a more physiologically pertinent primary model (organoids)? Human endometrial epithelial cells (ECC-1) were exposed to AGE at concentrations physiologically representative of uterine fluid in slender or obese subjects, as well as three potential therapeutics: 100 mol/l metformin, or a combination of antioxidants (10 mol/l N-acetyl-l-cysteine, 10 mol/l N-acetyl-l-carnitine, and 5 mol/l -lipoic acid). 

The adhesion and proliferation rates were determined by real-time cell analysis (xCELLigence, ACEA Biosciences). In the presence of AGE (n = 5), the proliferation of organoid-derived cells and the secretion of cytokines from organoids were characterized. (N = 77) Women undergoing assisted reproduction had their uterine fluid analyzed for AGE-associated inflammatory markers. AGE decreased ECC-1 proliferation in obese versus lean and vehicle-controlled conditions (P = 0.04 and P<0.001, respectively). In contrast, antioxidants restored ECC-1 proliferation to lean-like levels—donor-dependent AGE influence on organoid-derived primary endometrial epithelial cell proliferation. P = 0.006 indicates that AGE increased the organoid secretion of the proinflammatory cytokine CXCL16. 

Clinically, CXCL16 was positively correlated with maternal BMI (R = 0.264, P = 0.021) and intrauterine glucose concentration (R = 0.737, P<0.0001). AGE concentrations pertinent to physiology alter the function of endometrial epithelial cells. Antioxidants restore the proliferation rate of endometrial epithelial (ECC-1) cells treated with AGE. Primary endometrial epithelial cells cultured as organoids exhibit altered proliferation and CXCL16 secretion in the presence of AGE at concentrations equivalent to those found in the uterine fluid of obese individuals.

Source: sciencedirect.com/science/article/abs/pii/S1472648323000640