Shi Zhimin, Ding Lina, Zhang Hongxia, Feng Yixing, Xu Muqi, Dai Jiayin
Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Datun Road, Chaoyang District, Beijing, China.
Toxicol Lett. 2009 Aug 10;188(3):192-200. doi: 10.1016/j.toxlet.2009.04.014. Epub 2009 May 3.
Perfluorododecanoic acid (PFDoA), a synthetic perfluorinated chemical, has been detected in environmental matrices, wildlife, and human serum. Its potential health risk for humans and animals has raised public concern. However, the effects of chronic PFDoA exposure on male reproduction remain unknown. The aim of this study was to determine the effects of chronic PFDoA exposure (110 days) on testosterone biosynthesis and the expression of genes related to steroidogenesis in male rats. In this study, we examined the serum levels of sex hormones, growth hormone, and insulin in male rats. Testicular morphology and the expression of key genes and proteins in testosterone biosynthesis were also analyzed. Markedly decreased serum testosterone levels were recorded after 110 days of PFDoA exposure at 0.2mg PFDoA/kg/day and 0.5mg PFDoA/kg/day, and cast-off cells were observed in some seminiferous tubules in testes exposed to 0.5mg PFDoA/kg/day. PFDoA exposure resulted in significantly decreased protein levels of steroidogenic acute regulatory protein (StAR) and cholesterol side-chain cleavage enzyme (P450scc), along with significantly reduced mRNA levels of insulin-like growth factor I (IGF-I), insulin-like growth factor I receptor (IGF-IR), and interleukin 1alpha (IL-1alpha) in rat testes at 0.2mg/kg/day and 0.5mg/kg/day. In addition, PFDoA exposure also affected the expression of some genes in the hypothalamo-neurohypophyseal system. However, PFDoA did not affect the expression of 5alpha-reductase, 3alpha-hydroxysteroid dehydrogenase, or aromatase in testis and liver. These findings demonstrate that chronic PFDoA exposure disrupts testicular steroidogenesis and expression of related genes in male rats. Multiple factors may be involved in the inhibition of testosterone by PFDoA.
全氟十二烷酸（PFDoA）是一种合成的全氟化合物，已在环境基质、野生动物和人体血清中被检测到。其对人类和动物潜在的健康风险引起了公众关注。然而，长期暴露于PFDoA对雄性生殖的影响仍不清楚。本研究的目的是确定长期（110天）暴露于PFDoA对雄性大鼠睾酮生物合成及与类固醇生成相关基因表达的影响。在本研究中，我们检测了雄性大鼠血清中的性激素、生长激素和胰岛素水平。还分析了睾丸形态以及睾酮生物合成中关键基因和蛋白质的表达。在以0.2mg PFDoA/kg/天和0.5mg PFDoA/kg/天的剂量暴露于PFDoA 110天后，血清睾酮水平显著降低，并且在暴露于0.5mg PFDoA/kg/天的睾丸的一些生精小管中观察到脱落细胞。在0.2mg/kg/天和0.5mg/kg/天的剂量下，PFDoA暴露导致大鼠睾丸中类固醇生成急性调节蛋白（StAR）和胆固醇侧链裂解酶（P450scc）的蛋白水平显著降低，同时胰岛素样生长因子I（IGF-I）、胰岛素样生长因子I受体（IGF-IR）和白细胞介素1α（IL-1α）的mRNA水平也显著降低。此外，PFDoA暴露还影响了下丘脑 - 神经垂体系统中一些基因的表达。然而，PFDoA不影响睾丸和肝脏中5α-还原酶、3α-羟基类固醇脱氢酶或芳香化酶的表达。这些发现表明，长期暴露于PFDoA会破坏雄性大鼠睾丸的类固醇生成及相关基因的表达。PFDoA抑制睾酮的过程可能涉及多种因素。
