近日，《公共科学图书馆—综合》（PLoS One）刊登了中国科学院水生生物研究所鱼类基因工程学科组的研究论文（Defining Global Gene Expression Changes of the Hypothalamic-Pituitary-Gonadal Axis in Female sGnRH Antisense Transgenic Common Carp (Cyprinus carpio)）。该文报道了该学科组关于鱼类生殖发育调控机制研究的新进展。

“下丘脑-垂体-性腺（HPG）轴”在鱼类生殖发育和调控的过程中发挥着关键作用。该学科组采用反义转基因技术，通过特异阻遏鲤鱼GnRH基因的表达，成功研制出性腺发育被抑制的转基因鲤鱼（Aquaculture, 2007, 271：498–506）。性腺败育的转基因鲤鱼的获得，对于建立具有普遍意义的转基因鱼育性控制策略，从根本上解决人们对转基因鱼可能的生态风险的担忧具有重要意义；而且，GnRH基因的表达被抑制后，从源头上破坏了鱼类生殖发育调控网络的平衡，导致HPG轴的生殖相关信号因子发生改变，从而为开展鱼类生殖发育的调控机制研究提供了一个独特的模型。

在朱作言院士和胡炜研究员的指导下，博士研究生徐婧等利用抑制性差减杂交与基因芯片等技术，获得了转反义sGnRH基因鲤鱼及其对照鲤鱼HPG轴的差异表达基因谱，在转反义sGnRH基因鲤鱼下丘脑、垂体和性腺分离得到9、28和212个与生殖发育相关的差异表达基因。对所获得的差异表达基因进一步分析，发现上述基因涉及到组织生成、代谢途径、免疫系统与细胞凋亡等多种生物学功能，而且反义sGnRH对于生殖发育的调控作用通过HPG轴级联放大。神经肽、促性腺激素、生长激素、卵子生成与免疫相关因子等与鱼类生殖发育密切相关。

该研究获得了鱼类HPG轴及其调控网络中与生殖发育相关的基因及调控因子的广泛数据，为解析鱼类生殖发育的调控网络及其作用路径，进而为揭示鱼类生殖发育调控的机制提供了重要的科学资料。

原文出处：

PLoS ONE    DOI：10.1371/journal.pone.0021057

Defining Global Gene Expression Changes of the Hypothalamic-Pituitary-Gonadal Axis in Female sGnRH-Antisense Transgenic Common Carp (Cyprinus carpio)

JJing Xu, Wei Huang, Chengrong Zhong, Daji Luo, Shuangfei Li, Zuoyan Zhu, Wei Hu

Background The hypothalamic-pituitary-gonadal (HPG) axis is critical in the development and regulation of reproduction in fish. The inhibition of neuropeptide gonadotropin-releasing hormone (GnRH) expression may diminish or severely hamper gonadal development due to it being the key regulator of the axis, and then provide a model for the comprehensive study of the expression patterns of genes with respect to the fish reproductive system. Methodology/Principal Findings In a previous study we injected 342 fertilized eggs from the common carp (Cyprinus carpio) with a gene construct that expressed antisense sGnRH. Four years later, we found a total of 38 transgenic fish with abnormal or missing gonads. From this group we selected the 12 sterile females with abnormal ovaries in which we combined suppression subtractive hybridization (SSH) and cDNA microarray analysis to define changes in gene expression of the HPG axis in the present study. As a result, nine, 28, and 212 genes were separately identified as being differentially expressed in hypothalamus, pituitary, and ovary, of which 87 genes were novel. The number of down- and up-regulated genes was five and four (hypothalamus), 16 and 12 (pituitary), 119 and 93 (ovary), respectively. Functional analyses showed that these genes involved in several biological processes, such as biosynthesis, organogenesis, metabolism pathways, immune systems, transport links, and apoptosis. Within these categories, significant genes for neuropeptides, gonadotropins, metabolic, oogenesis and inflammatory factors were identified. Conclusions/Significance This study indicated the progressive scaling-up effect of hypothalamic sGnRH antisense on the pituitary and ovary receptors of female carp and provided comprehensive data with respect to global changes in gene expression throughout the HPG signaling pathway, contributing towards improving our understanding of the molecular mechanisms and regulative pathways in the reproductive system of teleost fish.