Zhang Dapeng, Xiong Huiling, Mennigen Jan A, Popesku Jason T, Marlatt Vicki L, Martyniuk Christopher J, Crump Kate, Cossins Andrew R, Xia Xuhua, Trudeau Vance L
Centre for Advanced Research in Environmental Genomics, Department of Biology, University of Ottawa, Ottawa, Ontario, Canada.
PLoS One. 2009 Jun 5;4(6):e5816. doi: 10.1371/journal.pone.0005816.
Many vertebrates, including the goldfish, exhibit seasonal reproductive rhythms, which are a result of interactions between external environmental stimuli and internal endocrine systems in the hypothalamo-pituitary-gonadal axis. While it is long believed that differential expression of neuroendocrine genes contributes to establishing seasonal reproductive rhythms, no systems-level investigation has yet been conducted.
METHODOLOGY/PRINCIPAL FINDINGS: In the present study, by analyzing multiple female goldfish brain microarray datasets, we have characterized global gene expression patterns for a seasonal cycle. A core set of genes (873 genes) in the hypothalamus were identified to be differentially expressed between May, August and December, which correspond to physiologically distinct stages that are sexually mature (prespawning), sexual regression, and early gonadal redevelopment, respectively. Expression changes of these genes are also shared by another brain region, the telencephalon, as revealed by multivariate analysis. More importantly, by examining one dataset obtained from fish in October who were kept under long-daylength photoperiod (16 h) typical of the springtime breeding season (May), we observed that the expression of identified genes appears regulated by photoperiod, a major factor controlling vertebrate reproductive cyclicity. Gene ontology analysis revealed that hormone genes and genes functionally involved in G-protein coupled receptor signaling pathway and transmission of nerve impulses are significantly enriched in an expression pattern, whose transition is located between prespawning and sexually regressed stages. The existence of seasonal expression patterns was verified for several genes including isotocin, ependymin II, GABA(A) gamma2 receptor, calmodulin, and aromatase b by independent samplings of goldfish brains from six seasonal time points and real-time PCR assays.
CONCLUSIONS/SIGNIFICANCE: Using both theoretical and experimental strategies, we report for the first time global gene expression patterns throughout a breeding season which may account for dynamic neuroendocrine regulation of seasonal reproductive development.
包括金鱼在内的许多脊椎动物都表现出季节性繁殖节律，这是下丘脑 - 垂体 - 性腺轴中外在环境刺激与内在内分泌系统相互作用的结果。长期以来，人们一直认为神经内分泌基因的差异表达有助于建立季节性繁殖节律，但尚未进行系统层面的研究。
方法/主要发现：在本研究中，通过分析多个雌性金鱼脑微阵列数据集，我们描绘了一个季节性周期的全局基因表达模式。下丘脑中有一组核心基因（873个基因）被鉴定为在五月、八月和十二月之间差异表达，这三个月份分别对应生理上不同的阶段，即性成熟（产卵前）、性消退和性腺早期再发育阶段。多变量分析显示，这些基因的表达变化在另一个脑区端脑中也有体现。更重要的是，通过检查从十月份处于典型春季繁殖季节（五月）的长日照光周期（16小时）下饲养的金鱼获得的一个数据集，我们观察到所鉴定基因的表达似乎受光周期调节；光周期是控制脊椎动物繁殖周期的一个主要因素。基因本体分析表明，激素基因以及在G蛋白偶联受体信号通路和神经冲动传递中功能相关的基因在一种表达模式中显著富集，这种表达模式的转变发生在产卵前和性消退阶段之间 通过从六个季节性时间点独立采集金鱼脑样本并进行实时PCR分析，验证了包括异催产素、ependymin II、GABA(A)γ2受体、钙调蛋白和芳香化酶b在内的几个基因存在季节性表达模式。
结论/意义：我们首次使用理论和实验策略报告了整个繁殖季节的全局基因表达模式，这可能解释了季节性繁殖发育的动态神经内分泌调节。
