壬基酚聚氧乙烯醚对成年雄性斑马鱼HPG轴相关基因表达的影响

本研究以模式动物斑马鱼（Danio rerio）为受试生物，采用半静态水体暴露的方式研究了不同浓度壬基酚聚氧乙烯醚（NPEO）对斑马鱼雄性成鱼下丘脑-垂体-性腺轴（HPG轴）的影响.结果显示，考察浓度范围内的NPEO暴露可以显著上调斑马鱼脑中GnRH2、GnRHR1、GnRHR2、GnRHR4、FSHβ和LHβ基因，以及性腺中LHR基因的相对表达量.GnRHR和LHR基因表达量对较低浓度NPEO暴露较为敏感，其中GnRHR4和LHR基因表达量在低至0.001mg/L的NPEO暴露下即出现显著上调.0.1和10mg/L NPEO暴露可以显著抑制斑马鱼精巢中CYP17基因的表达量，而10mg/L NPEO暴露则可以显著诱导CYP19a基因的表达量.GnRH相关调控基因表达量的上调，表明NPEO暴露可以诱导下丘脑分泌GnRH，进而刺激垂体分泌GtH.NPEO暴露诱导CYP19a基因的表达，促进了内源雌激素的合成.同时，NPEO通过抑制CYP17表达，可能抑制睾酮（T）的合成，干扰斑马鱼精巢中原有的性激素平衡.斑马鱼精巢内雌激素水平升高负反馈给垂体，刺激垂体分泌促性腺激素.由此表明，考察浓度范围内（0.001~10mg/L）的NPEO的暴露可以影响雄性斑马鱼成鱼HPG轴的反馈调节.

Effects of nonylphenol ethoxylate exposure on genes expression along HPG axis of adult male zebrafish

In the present study, the semi-static exposure test method was used for elucidating the effects of different concentrations of nonylphenol polyethylene glycol ether (NPEO) on the hypothalamic-pituitary-gonadal axis (HPG axis) of adult male zebrafish (Danio rerio). The results showed that the expressions of GnRH2, GnRHR1, GnRHR2, GnRHR4, FSHβ and LHβ genes in the brain, as well as the expression of LHR gene in the testis of zebrafish were significantly up-regulated under the exposure of NPEO at the experimental concentrations. The expressions of GnRHR and LHR genes were sensitively to the NPEO exposure at relatively low concentrations and the most sensitive biomarkers were the expressions of GnRHR4 and LHR genes, which were significantly induced under the exposure to 0.001mg/L of NPEO. The expression of CYP17 gene was significantly inhibited in the testis of fish exposed to NPEO at 0.1 and 10mg/L NPEO and on the contrary, the expression of CYP19a gene was significantly induced in the 10mg/L of NPEO group. Up-regulation of GnRH gene indicated that the exposure to NPEO could induce the secretion of GnRH in the hypothalamus and stimulate the secretion of GtH in the pituitary of zebrafish in turn. The exposure to NPEO could promote the synthesis of endogenous estrogen in zebrafish by up-regulating the expression of CYP19a gene and inhibit the synthesis of testosterone (T) by down-regulating the expression of CYP17 gene, and therefore disrupt the sexual hormone homeostasis in zebrafish. The increased levels of estrogen in the testis of zebrafish could produce the negative feedback to the pituitary gland and then stimulated the secretion of GtH in the pituitary, suggesting that NPEO at the experimental concentrations (0.001~10mg/L) could affect the feedback regulation of the HPG axis in male adult zebrafish.