Tributyltin reduces bone mineral density by reprograming bone marrow mesenchymal stem cells in rat.

Tributyltin (TBT), a proven endocrine disrupter, was widely used in industry and agriculture. Previous research showed that TBT could alter the balance between osteogenesis and adipogenesis, which may have significant consequences for bone health. Herein, we exposed male rats to TBT chloride (TBTCl) to evaluate the deleterious effects of TBT on bone. Exposure to 50 µg kg-1 TBT resulted in a significant decrease in bone mineral density (BMD) at the femur diaphysis region in the rat. A dose-dependent increase in lipid accumulation and adipocyte number was observed in the bone marrow (BM) of the femur. Meanwhile, TBTCl treatment significantly enhanced the expression of PPARγ and attenuated the expression of Runx2 and ß-catenin in BM. In addition, serum ALP activity of TBT-exposed rats also showed a dose-dependent decrease. These results suggest that TBT could reduce BMD via inhibition of the Wnt/ß-catenin pathway and skew the adipo-osteogenic balance in the BM of rats.

Tributyltin exposure induces gut microbiome dysbiosis with increased body weight gain and dyslipidemia in mice.

Gut microbiome dysbiosis plays a profound role in the pathogenesis of obesity and tributyltin (TBT) has been found as an environmental obesogen. However, whether TBT could disturb gut microbiome and the relationship between obesity induced by TBT exposure and alteration in gut microbiota are still unknown. In order to assess the association between them, mice were exposed to TBTCl (50 µg kg-1) once every three days from postnatal days (PNDs) 24 to 54. The results demonstrated that TBT exposure resulted in increased body weight gain, lager visceral fat accumulation and dyslipidemia in male mice on PND 84. Correspondingly, 16S rRNA gene sequencing revealed that TBT treatment decreased gut microbial species and perturbed the microbiome composition in mice. Furthermore, Pearson's corelation coefficient analysis showed a significantly negative correlation between the body weight and the alpha diversity of gut microbiome. These results suggested that TBT exposure could induce gut microbiome dysbiosis in mice, which might contribute to the obesity pathogenesis.