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国家自然科学基金(31071018)

作品数:3 被引量:19H指数:2
相关作者:李喜霞刘以训郑乔松季韶洋张君更多>>
相关机构:中国科学院中国科学院大学更多>>
发文基金:国家自然科学基金国家重点基础研究发展计划北京市自然科学基金更多>>
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隐睾不育的分子基础被引量:9
2010年
隐睾症或热局部处理猴和大鼠睾丸,能引起可逆性生精细胞凋亡,出现少精或无精现象.43℃局部热浴猴睾丸可引起精液中精子数量发生可逆性减少.睾丸支持细胞为生精细胞提供结构支持与营养供给.生精上皮中支持细胞间以及支持细胞和各级生精细胞间的特殊连接在精子发生中起着至关重要的作用.本研究组发现,热处理后紧密连接分子,如occludin,zonula occludens-1(ZO-1)在24~48h表达明显下降,血睾屏障(blood-testis barrier,BTB)发生了可逆性破坏.该过程还伴随着TGF-β2和TGF-β3表达增高,p38MAPK和ERK/MAPK信号通路激活.由此推测,热激可能通过引发TGF-βs增高,下调紧密连接相关蛋白的表达,导致细胞连接减弱,从而引起BTB结构发生可逆性紊乱.此外,本文还综述了成年小鼠实验性隐睾睾丸中总基因的表达变化,成功克隆了几个生理功能显著,与精子发生特异相关的新基因.
刘以训李喜霞
关键词:隐睾精子发生热激支持细胞血睾屏障
Sf1,Wnt和cAMP信号通路协同参与抑制素α基因转录的调控被引量:1
2013年
抑制素仪是抑制素组成性蛋白的亚基之一.它广泛表达于睾丸、卵巢和肾上腺.敲除抑制素α亚基的雄性小鼠常具有性腺基质细胞瘤的表型,这提示,抑制素α亚基可能在性腺发育过程中发挥重要的作用.据报道,类固醇生成因子1(Sf1)能与Wnt或cAMP信号通路协同诱导抑制素α亚基的表达,然而Sf1,Wnt和cAMP信号通路协同调控抑制素α亚基表达的分子机制仍然未知.本研究发现,cAMP和wnt信号通路对于协同Sf1转录调控抑制素α亚基的表达是至关重要的.抑制素α亚基启动子上的CRE位点(cAMP反应元件)的特异突变,能够完全消除Sf1和wnt信号通路的协同调控作用.本研究还发现,cAMP信号通路参与的协同调控抑制素α亚基的表达是通过CRE结合蛋白(CREB-1)介导实现的.利用CREB-1特异的shRNA敲降CREB-1的蛋白水平,能够消除cAMP信号通路参与的协同调控抑制素α亚基的表达.此外,特异的突变Sf1蛋白配体结合域(LBD区)的氨基酸残基235—238能够影响Sf1和cAMP信号通路协同调控抑制素α亚基的转录表达,这表明,Wnt信号通路参与了Sf1和cAMP信号通路协同调控抑制素α亚基转录表达的过程.
季韶洋李蕾李喜霞张君郑乔松陈军高飞刘以训
关键词:CAMP
Molecular basis of cryptorchidism-induced infertility被引量:9
2010年
Artificial cryptorchidism or local testicular heat treatment can induce reversible oligospermia or azoospermia in monkeys and rats via germ cell apoptosis. Local warming of monkey testes in water at 43°C for 2 consecutive days (30 min per day) decreased the number of sperm in the semen by up to 80% on d 28, and the effect was completely reversed on d 144. Germ cells rely heavily on Sertoli cells for structural and nutritional support. Specialized junctions that play a pivotal role in spermatogenesis occur at sites of Sertoli-Sertoli and Sertoli-germ cell contact in the seminiferous epithelium. We demonstrated that expression of tight junction (TJ)-associated molecules, such as occludin and zonula occludens-1 (ZO-1), were greatly reduced 24–48 h after heat treatment, while the permeability of the blood-testis barrier (BTB) was simultaneously increased, but recovered 10 d later. These results indicate a reversible disruption of the BTB associated with transient inductions of transforming growth factor (TGF) β2 and β3 expression, p38 mitogen-activated protein kinase and extracellular signal-regulated kinase activation, and concomitant loss of occludin and ZO-1. This suggests that expression of TJ-associated molecules and the BTB was reversibly perturbed by mild testicular hyperthermia, and that the heat-induced induction of TGF-β might be involved in downregulating TJ-associated proteins, leading to cell junction reduction. This review discusses the changes in total gene expression patterns after experimental cryptorchidism in adult mouse testes, and the cloning of several novel, physiologically significant spermatogenesis-specific genes.
LIU YiXun & LI XiXia State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China
关键词:CRYPTORCHIDISMSPERMATOGENESISSERTOLITIGHTJUNCTION
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