实验动物与比较医学 ›› 2020, Vol. 40 ›› Issue (4): 296-.DOI: 10.3969/j.issn.1674-5817.2020.04.005

• 论著 • 上一篇    下一篇

泛素羧基末端水解酶1基因缺失对雌性小鼠生殖系统发育的影响

吴   比,梁珊珊,阮井玲,黄   鑫,滕晓明,洪   岭   

  1. 同济大学附属第一妇婴保健院辅助生殖科,上海 200001

  • 出版日期:2020-08-25 发布日期:2020-11-20
  • 作者简介:吴 比(1986—), 女, 博士, 主管技师, 研究方向: 生殖内分泌及辅助生殖。E-mail: biowubi@163.com
  • 基金资助:
    同济大学国家自然科学基金项目校内培育项目 (22120180406)

Effect of Ubiquitin C-terminal Hydrolase 1 Gene Deletion on Reproductive System Development in Female Mice

WU Bi, LIANG Shanshan, RUAN Jingling, HUANG Xin, TENG Xiaoming, HONG Ling   

  1. Department of Assisted Reproductive Medicine, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 200001, China)
  • Online:2020-08-25 Published:2020-11-20

摘要: 目的    研究泛素羧基末端水解酶L1(ubiquitin C-terminal hydrolase L1,UCH-L1)基因缺失对雌性小鼠生殖系统的影响。方法    利用阴道涂片、免疫组织化学、蛋白质印迹和RNA干扰等方法,分析UCH-L1基因缺失对小鼠卵巢功能及卵泡发育的影响。结果    UCH-L1基因缺失纯合子成年雌性小鼠的体质量降低,运动困难,且子宫偏细。在UCH-L1基因缺失纯合子小鼠的卵巢和子宫中检测不到UCH-L1蛋白表达,卵巢体积明显小于杂合子小鼠,其卵巢皮质层存在一些原始卵泡或闭锁卵泡,没有成熟卵泡和黄体。雌激素受体(estrogen receptor,ER)、卵泡刺激素受体(follicle-stimulating hormone receptor,FSHR)、黄体生成素受体(luteinizing hormone receptor,LHR)及孕酮受体(progesterone receptor,PR)等生殖关键受体在UCH-L1缺失纯合子小鼠和杂合子小鼠卵巢中都有表达,其中纯合子小鼠卵巢中ER的表达水平明显低于杂合子小鼠。通过RNA干扰的方法下调生发泡(germinal vesicle, GV)期卵母细胞中UCH-L1的表达,能明显降低卵母细胞的成熟率。结论    UCH-L1基因缺失雌性小鼠不具备形成成熟卵泡及排卵的能力,卵巢中ER表达量显著降低。 推测UCH-L1有可能通过下调卵巢中ER的表达,影响卵母细胞成熟及排卵过程。

关键词: 卵巢, 卵母细胞成熟, 泛素羧基末端水解酶1, 小鼠

Abstract:  Objective    To study the effect of ubiquitin C-terminal hydrolase-L1 (UCH-L1) gene deletion on the reproductive system of female mice. Methods     Vaginal smears, immunohistochemistry, Western blotting and RNA interference methods were used to analyze the effects of UCH-L1 gene deletion on the ovarian function and follicle development in mice. Results    The adult female mice with UCH-L1 deletion had lower body weight, dyskinesia and thinner uterus. No UCH-L1 protein expression was detected in the ovaries and uteruses of UCH-L1-deleted homozygous mice, and the ovary volume was significantly smaller than that of heterozygous mice. There were some primitive or closed follicles in the ovarian cortex, and there was no mature follicle and corpus luteum. The key reproductive receptors including estrogen receptor (ER), follicle-stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR) and progesterone receptor (PR) were expressed in the ovary of UCH-L1-deleted homozygous and heterozygous mice. The expression level of ER in the ovary of UCH-L1-deleted homozygous mice was significantly lower than that of heterozygous mice. By RNA interference, knocking down the expression of UCH-L1 in germinal vesicle (GV) oocytes could significantly reduce the maturation rate of oocytes. 

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