Tributyltin increases the expression of apoptosis- and adipogenesis-related genes in rat ovaries.
Tributyltin increases the expression of apoptosis- and adipogenesis-related genes in rat ovaries.
复制标题
DOI：
10.5653/cerm.2012.39.1.15
复制
发表时间：
2012-03
期刊：
影响因子：
--
通讯作者：
Yang H
中科院分区：
文献类型：
--
作者：
Lee H;Lim S;Yun S;Yoon A;Park G;Yang H
三丁基锡（TBT）是一种内分泌干扰化学物质，有报道称其通过引起卵巢细胞凋亡而降低卵巢功能，但其机制尚不完全清楚。因此，我们研究了TBT是否增加了卵巢中脂肪形成相关基因的表达，以及这些基因的表达增加是否与诱导细胞凋亡有关。3周龄Sprague-Dawley大鼠口服TBT（1或10 mg/kg体重）或香油作为对照，连续7 d。第8天取卵巢称重，固定后进行末端脱氧核苷酸转移酶dUTP缺口末端标记（TUNEL）或冷冻提取RNA。采用实时聚合酶链反应（real-time polymerase chain reaction， PCR）分析卵巢总RNA中脂肪生成和细胞凋亡相关基因。与对照组相比，10 mg/kg TBT组卵巢重量显著降低。TUNEL实验显示，给药10 mg/kg TBT后，大鼠卵巢凋亡卵泡数量显著增加。real-time PCR结果显示，TBT给药后，脂肪生成相关基因PPARγ、aP2、CD36、PEPCK的表达增加。此外，与对照大鼠相比，tbt给药大鼠的凋亡相关基因如TNFα和TNFR1表达更多。本研究表明，TBT诱导卵巢脂肪生成和细胞凋亡相关基因的表达，导致卵巢卵泡细胞凋亡。这些结果表明，TBT暴露导致卵巢脂肪生成相关基因表达增加可能诱导细胞凋亡，导致卵巢功能丧失。
Tributyltin (TBT), an endocrine disrupting chemical, has been reported to decrease ovarian function by causing apoptosis in the ovary, but the mechanism is not fully understood. Therefore, we examined whether TBT increases the expression of adipogenesis-related genes in the ovary and the increased expression of these genes is associated with apoptosis induction. Three-week-old Sprague-Dawley rats were orally administered TBT (1 or 10 mg/kg body weight) or sesame oil as a control for 7 days. The ovaries were obtained and weighed on day 8, and then they were fixed for terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) or frozen for RNA extraction. Using the total RNA of the ovaries, adipogenesis- and apoptosis-related genes were analyzed by real-time polymerase chain reaction (PCR). The ovarian weight was significantly decreased in rats administered 10 mg/kg TBT compared to that in control rats. As determined by the TUNEL assay, the number of apoptotic follicles in ovary was significantly increased in rats administered 10 mg/kg TBT. The real-time PCR results showed that the expression of adipogenesis-related genes such as PPARγ, aP2, CD36, and PEPCK was increased after TBT administration. In addition, apoptosis-related genes such as TNFα and TNFR1 were expressed more in the TBT-administered rats compared with the control rats. The present study demonstrates that TBT induces the expression of adipogenesis- and apoptosis-related genes in the ovary leading to apoptosis in the ovarian follicles. These results suggest that the increased expression of adipogenesis-related genes in the ovary by TBT exposure might induce apoptosis resulting in a loss of ovarian function.