Neonatal exposure to environment-relevant levels of tributyltin leads to uterine dysplasia in rats.

Endocrine-disrupting chemicals (EDCs) are natural/synthetic compounds that mimic or inhibit the biological actions of endogenous hormones. Studies have revealed that environmental estrogen, such as bisphenol A (BPA), causes developmental defects in the uterus. Tributyltin (TBT) is a typical environmental androgen. In this study, we aimed to explore the effect and mechanism of TBT on uterine development. Neonatal female rats were exposed to TBT (10 and 100 ng/kg bw) from postnatal days 1 to 16. BPA (50 μg/kg bw) was used as a positive control. Neonatal exposure to environmental concentrations of TBT resulted in pathological changes in the uterus, including thickening of the uterine luminal epithelium, a low density of glands, endometrial inflammation and fibrosis. Further, TBT affected the Wnt signaling pathway, which might mediate developmental disorders of the endometrial epithelial cells and glands in the uterus. TBT exposure also activated the NF-κB signaling pathway, which triggered inflammation. Moreover, TBT exposure upregulated the TGF-β/Smads signaling pathway, possibly leading to endometrial fibrosis. In summary, our results demonstrate that neonatal exposure to an environment-relevant level of TBT leads to uterine dysplasia and provide potential molecular mechanisms. Our study is helpful for clarifying the effects of environmental androgens on the female reproduction system. Unlabelled Image • TBT caused uterine dysplasia in rats. • TBT influenced endometrial development possibly via the Wnt signaling pathway. • TBT activated the NF-κB signaling pathway and caused inflammation. • TBT up-regulated TGF-β1/Smads signaling pathway and caused uterine endometrial fibrosis. [ABSTRACT FROM AUTHOR]