Abstract:

In areas with coal mines, there are concerns about increased human exposure to elevated levels of selenium and adverse pregnancy outcomes. Cortisol, which plays a role in the development of the placenta, has been shown to be dysregulated following exposure to selenium. As cortisol is also associated with placental dysfunction, and placental dysfunction underlies many adverse pregnancy outcomes, this study investigated how selenium exposure impacts placental invasion, migration, and angiogenesis, and the role of glucocorticoids in these processes. HTR-8/SVneo cells (human first-trimester trophoblasts) were exposed to environmentally relevant concentrations of sodium selenite (NaSe) for 24 or 48h. Cortisol was measured via ELISA, migration and invasion were measured via a wound-healing assay and invasion assay, respectively, and steady-state mRNA expression of genes involved in glucocorticoid homeostasis, and invasion, migration, and angiogenesis were measured by qPCR. NaSe treatment caused increased cortisol and induced genes that are indicative of glucocorticoid receptor (GR) activation. NaSe also induced genes involved in the regulation of invasion, migration and angiogenesis. NaSe decreased migration but did not affect invasion. When cells were co-treated with NaSe and either 1) metyrapone (inhibitor of cortisol synthesis), or 2) mifepristone (GR antagonist), the expression of genes associated with increased cortisol did not decrease, suggesting that selenium may be activating the glucocorticoid pathway through alternate means. These data suggest that exposure to NaSe perturbs trophoblast function and glucocorticoid regulation. Perturbations of trophoblast cell function may lead to problems in placental function, increasing the risk of poor pregnancy outcomes. Future work will identify how selenium is activating the glucocorticoid pathway to understand selenium’s impact on trophoblast function.