Tributyltin에 의한 흰쥐 정소 내 간질세포의 지방세포 유도와 세포자연사 증가
Tributyltin Increases Adipogenesis and Apoptosis of Rat Testicular Interstitial Cells
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Tributyltin (TBT), an endocrine disrupting chemical, has been reported to decrease testicular function by causing apoptosis in the testis, but this mechanism is not fully understood. Thus, in this study we examined whether TBT induces adipogenesis of the Leydig cells to find out the correlation between adipogenesis and apoptosis in the testis. Three week old SD male rats were orally administrated with sesame oil, 1 ㎎/㎏ of TBT, or 10 mg/㎏ of TBT daily for 1 week and weighed after administration. The testes obtained on day 8 were weighed and stained with BODIPY and TUNEL kit. Using total RNA extracted from the isolated Leydig cells, adipogenesis and apoptosis-related genes were analyzed by real-time PCR. The testicular weights of the rats treated with 10 ㎎/㎏ TBT were significantly decreased compared to those in the control rats treated with sesame oil. As a result of BODIPY staining, the number of Leydig cells stained with BODIPY was increased in the rats treated with 10 ㎎/㎏ TBT compared with the control rats. Similar to BODIPY staining results, the TUNEL assay showed that the apoptosis of Leydig cells was increased in TBT treated rats. The results of the gene expression analysis in the Leydig cells showed that the expression of adipogenesis-related genes (PPARγ, aP2, Perilipin, CD36) and apoptosis-related genes (TNFRSF1A, TNFSF10) was increased after TBT administration. The present study demonstrates that TBT induces the expression of adipogenesis-related and apoptosis-related genes in the Leydig cells leading to adipogenesis and apoptosis in the testes. These results suggest that the dysfunction of Leydig cells by TBT exposure may cause a loss in testicular function.
Abstract
Tributyltin (TBT), an endocrine disrupting chemical, has been reported to decrease testicular function by causing apoptosis in the testis, but this mechanism is not fully understood. Thus, in this study we examined whether TBT induces adipogenesis of the Leydig cells to find out the correlation between adipogenesis and apoptosis in the testis. Three week old SD male rats were orally administrated with sesame oil, 1 ㎎/㎏ of TBT, or 10 mg/㎏ of TBT daily for 1 week and weighed after administration. The testes obtained on day 8 were weighed and stained with BODIPY and TUNEL kit. Using total RNA extracted from the isolated Leydig cells, adipogenesis and apoptosis-related genes were analyzed by real-time PCR. The testicular weights of the rats treated with 10 ㎎/㎏ TBT were significantly decreased compared to those in the control rats treated with sesame oil. As a result of BODIPY staining, the number of Leydig cells stained with BODIPY was increased in the rats treated with 10 ㎎/㎏ TBT compared with the control rats. Similar to BODIPY staining results, the TUNEL assay showed that the apoptosis of Leydig cells was increased in TBT treated rats. The results of the gene expression analysis in the Leydig cells showed that the expression of adipogenesis-related genes (PPARγ, aP2, Perilipin, CD36) and apoptosis-related genes (TNFRSF1A, TNFSF10) was increased after TBT administration. The present study demonstrates that TBT induces the expression of adipogenesis-related and apoptosis-related genes in the Leydig cells leading to adipogenesis and apoptosis in the testes. These results suggest that the dysfunction of Leydig cells by TBT exposure may cause a loss in testicular function.
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