Abstract:

Introduction: Active coal mining and other human activities contribute to the accelerated release of selenium (Se) into the surrounding environment. Although Se is an essential trace element that is vital for antioxidant defense, its bioaccumulation raises concerns due to its toxic reproductive effects in various species. Studies have previously shown that increased Se exposure can produce reproductive deficits in fish, but its role in mammalian reproductive function has not been fully characterized. Notably, Se exposure has been reported to cause premature aging (senescence). Since increased cell senescence in the placenta is associated with adverse pregnancy outcomes, the goal of this study was to determine if exposure to NaSe alters markers of cellular senescence in placental trophoblast cells. Methods and Results: HTR-8/SVneo cells, a trophoblast model, were exposed to NaSe (0.1, 0.2, 0.5, 1 and 2 μM) for 24 hours to assess the mRNA expression of the following gene markers of cell senescence (TP53, P21, P16lnk4a) and cytokines indicative of the senescence-associated secretory phenotype ( IL1β, IL15, IL6). Active coal mining in Alberta and British Columbia have increased Se concentrations in surrounding waters; the Se concentrations for this study were determined to be representative of Se exposure in regions affected by anthropogenic activities. NaSe exposure at lower concentrations (0.1, 0.2 and, 0.5 μM) significantly increased TP53 and IL15 mRNA expression while higher doses (1 and 2 μM) significantly increased P16lnk4a and P21 expression, respectively. IL1β expression increased significantly at both 0.1 and 0.2 μM whereas IL6 expression decreased at lower doses, and increased significantly at 2 μM. Conclusion: These findings suggest that NaSe exposure may induce cellular senescence in placental trophoblasts, providing further insight into the mechanisms by which Se may adversely impact reproductive function in mammals.