GH/GHR信号通路调控鱼类卵细胞发育分子机制研究

Growth and reproduction are both important traints in fish breeding, their regulative system is closely related. Growth hormone (GH) is a key factor in stimulating body growth in teleost. The GH transgenic fish，such as common carp, tilapia, and Atlantic salmon, which over express gh gene in their bodies commonly show decrease fecundity. The oocyte development dramaticlly delays in the GH transgenic female compared with non-trangenic female. Growth hormone receptor (GHR) as studies showed is expressed in fish follicles, which could directly receive GH stimulation and affect the development of oocytes. The function of GH in regulating oocyte development is coming to concern. In this project, we will use GH transgenic common carp (Cyprinus carpio L.) and GHR gene knock out zebrafish (Danio rerio) as a model. The effects of GH/GHR signaling pathway on oocyte growth, estrogen production, and TGF-β superfamily genes expression are to be studied. The phosphorylation of cell signaling pathway factors, such as Erk and Akt, is to be examined in follicle treated with GH in vitro. We aim for exploring the mechanism of GH/GHR signaling pathway in regulating fish oocytes development, and revealing the relationship between growth and reproduction in fish. It is helpful to guid fish genetic breeding in our future work.

生长和生殖是鱼类育种重要的两个性状，两者的调控系统密切联系。生长激素（Growth Hormone, GH）是鱼类生长关键促进因子。人工培育的转GH基因鱼除具有快速生长特性外，普遍表现出生殖力下降、卵细胞发育滞后的特征。鱼类卵巢细胞表达有生长激素受体（Growth Hormone Receptor, GHR），可直接接受GH的刺激作用。因此，GH/GHR信号通路可能在调控卵细胞发育中发挥非常重要的功能，但机制尚不清楚。本项目以转“全鱼”生长激素基因鲤为模型，结合创制GHR基因敲除缺失GH/GHR信号通路功能的斑马鱼，分析卵巢细胞内GH/GHR信号通路的传导路径及其对卵泡生长、雌激素合成、TGF-β超家族成员基因表达的调控作用。本项目旨在探索GH/GHR信号通路调控鱼类卵细胞发育的分子机制，以期揭示鱼类生长与生殖间的调控关系。研究结果对于指导鱼类优良养殖品种的培育具有重要应用价值。

鱼类生长和生殖是育种研究关注的重要性状。生长激素（Growth Hormone, GH）在调控鱼类生长和生殖均发挥着重要功能。本研究发现高表达生长激素的雌性鲤鱼体内雌二醇含量显著下降，雄性鲤鱼体内睾酮和11酮基睾酮含量也显著下降，转gh基因鲤鱼卵细胞发育和精子生成滞后于野生鲤鱼。转gh基因鲤鱼体内脂肪含量减少，肠绒毛的数量和高度则显著增加。本研究研制了ghra和ghrb基因突变的斑马鱼模型以研究GH/GHR信号通路缺失对生长和生殖的影响。结果表明ghra或ghrb单突变对斑马鱼的生长和生殖均没有明显影响，ghra和ghrb双突变时斑马鱼生长停滞在青春启动期，性腺发育也明显滞后与正常的斑马鱼。GH/GHR信号通路缺失的雌性斑马鱼体内雌二醇含量显著降低、雄性斑马鱼体内睾酮、11酮基睾酮的含量也显著降低。双突变斑马鱼体内皮下脂肪层显著增厚，肠绒毛的数量和高度显著减少。研究结果表明鱼类体内过高的生长激素水平和缺乏生长激素信号通路均影响生殖发育，鱼类育种中采用转生长激素基因的方式促进生长需要保持体内生长激素含量在一定的范围。本研究还发现斑马鱼早期卵细胞的增殖和凋亡直接影响性腺分化的方向，阐明了鱼类性腺体细胞起源于性腺上皮层组织。本研究还揭示了鱼类生殖调控轴上游因子Kisspeptin2、GnIH在脑部和垂体中的分布模式，阐明了Kisspeptin2、GnIH调控生殖的功能。

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