Journal
TOXICOLOGY LETTERS
Volume 322, Issue -, Pages 39-49Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2020.01.001
Keywords
Organotin; 11beta-hydroxysteroid dehydrogenase; Retinoid X receptor alpha; Placenta; Glucocorticoid
Categories
Funding
- Swiss Centre for Applied Human Toxicology
- Swiss Federal Laboratories for Materials Science and Technology
Ask authors/readers for more resources
Exposure to the environmental pollutants organotins is of toxicological concern for the marine ecosystem and sensitive human populations, including pregnant women and their unborn children. Using a placenta cell model, we investigated whether organotins at nanomolar concentrations affect the expression and activity of 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2). 11 beta-HSD2 represents a placental barrier controlling access of maternal glucocorticoids to the fetus. The organotins tributyltin (TBT) and triphenyltin (TPT) induced 11 beta-HSD2 expression and activity in JEG-3 placenta cells, an effect confirmed at the mRNA level in primary human trophoblast cells. Inhibition/knock-down of retinoid X receptor alpha (RXR alpha) in JEG-3 cells reduced the effect of organotins on 11 beta-HSD2 activity, mRNA and protein levels, revealing involvement of RXR alpha. Experiments using RNA and protein synthesis inhibitors indicated that the effect of organotins on 11 beta-HSD2 expression was direct and caused by increased transcription. Induction of placental 11 beta-HSD2 activity by TBT, TPT and other endocrine disrupting chemicals acting as RXR alpha agonists may affect placental barrier function by altering the expression of glucocorticoid-dependent genes and resulting in decreased availability of active glucocorticoids for the fetus, disturbing development and increasing the risk for metabolic and cardiovascular complications in later life.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available