{Reference Type}: Journal Article {Title}: Effects of Liquid Fructose Supplementation and Chronic Unpredictable Stress on Uterine Contractile Activity in Nonpregnant Rats. {Author}: Oreščanin Dušić Z;Kovačević S;Ristić N;Vojnović Milutinović D;Vidonja Uzelac T;Blagojević D;Djordjevic A;Brkljačić J; {Journal}: Int J Mol Sci {Volume}: 25 {Issue}: 12 {Year}: 2024 Jun 20 {Factor}: 6.208 {DOI}: 10.3390/ijms25126770 {Abstract}: Increased fructose consumption and chronic stress, the major characteristics of modern lifestyle, impact human health; however, the consequences of their combination on the uterus remain understudied. In this study, we investigated contractile activity, morphology, and intracellular activity of antioxidant enzymes in uteri from virgin Wistar rats subjected to liquid fructose supplementation and/or unpredictable stress over 9 weeks. Contractile activity and uterine response to oxytocin or adrenaline were examined ex vivo using isolated bath chambers. Fructose supplementation, irrespective of stress, affected uterine morphology by increasing endometrium while decreasing myometrium volume density, attenuated uterine response to increasing doses of oxytocin, and increased glutathione peroxidase activity. Stress, irrespective of fructose, attenuated dose-dependent adrenaline-induced uterine relaxation. Stress, when applied solely, decreased mitochondrial superoxide dismutase activity. In the combined treatment, irregular estrous cycles and both reduced response to oxytocin and to adrenaline (as a consequence of fructose consumption and exposure to stress), along with fructose-related alteration of uterine morphology, were detected. In conclusion, fructose and stress affect uterine contractile activity, irrespective of each other, by inducing completely distinct responses in isolated uteri. In the combined treatment, the effects of both factors were evident, suggesting that the combination exerts more detrimental effects on the uterus than each factor individually.