The effects of in ovo tributyltin exposure on PPARγ-RXRα signaling and development in the American alligator

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Bernhard, Melissa Claire
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For the majority of the last half of the twentieth century and into the early 2000s, tributyltin (TBT) was used as an antifoulant on boat hulls as well as in other products. It has been banned in numerous countries due to its effects on gastropods, causing imposex (induced growth of male reproductive organs on adult females). More recently, TBT has been investigated as an obesogenic endocrine disruptor. Obesogens activate the peroxisome proliferator-activated receptor gamma (PPARγ) - retinoid x receptor alpha (RXRα) heterodimer, which together stimulate adipogenesis. TBT is an agonist for this in mammals. However, its effects in other animal groups, including non-avian reptiles is unknown. The American alligator has been investigated for endocrine disruption as a sentinel species because it exhibits temperature-dependent sex determination (TSD), which is very sensitive to endocrine signaling during development. To investigate the effects of developmental exposure to an obesogen, alligators were exposed in ovo to TBT prior to the thermosensitive period for TSD. Toxicity and a hatchout delay were observed in TBT treated eggs, and no effects on sex ratios were seen. Effects of the obesogen exposure in ovo were limited to decreased tail girth after one week, but transactivation via alligator PPARγ-RXRα on both PPAR and RXR response elements was induced by TBT exposure measured by an in vitro reporter gene assay. Thus, TBT has potential as obesogen, but further investigations are required to understand the effect seen in the tail.
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