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选择性胰岛素样生长因子-I 拮抗剂以剂量依赖的方式抑制小鼠胚胎发育。

Selective insulin-like growth factor-I antagonist inhibits mouse embryo development in a dose-dependent manner.

机构信息

Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.

出版信息

Fertil Steril. 2010 May 15;93(8):2621-6. doi: 10.1016/j.fertnstert.2009.12.044.

DOI:10.1016/j.fertnstert.2009.12.044
PMID:20138270
Abstract

OBJECTIVE

To study the role of a synthetic insulin-like growth factor-I receptor (IGF-IR) antagonist, picropodophyllin, for mouse preimplantation embryo development in vivo and in vitro.

DESIGN

In vitro and in vivo study.

SETTING

Hospital-based research unit.

ANIMALS

FVB/N mice and mouse embryos.

INTERVENTION(S): The effect of picropodophyllin in mouse embryo development in vivo and in vitro, immunohistochemistry, ELISA, polymerase chain reaction.

MAIN OUTCOME MEASURE(S): Embryo development, presence of IGF-IR, messenger RNA expression, IGF-I synthesis.

RESULT(S): The effect of picropodophyllin on embryo development in vitro and in vivo was not reversible. Mice treated with picropodophyllin 1 to 3 days after mating had a reduced number of blastocysts, 40.5% versus 78.8%, and a higher number of embryos with delayed development, 48.6% versus 11.5%. Insulin-like growth factor-IR protein is present in both phosphorylated and nonphosphorylated form at all stages of embryo development. The relative IGF-IR messenger RNA expression was highest in the oocyte and reduced during development to blastocyst stage. Insulin-like growth factor-I in culture media was reduced after picropodophyllin treatment.

CONCLUSION(S): We conclude that IGF-I has an important role in normal mouse embryo development and that its receptor plays an essential role in the embryonic genome activation process.

摘要

目的

研究合成胰岛素样生长因子-I 受体(IGF-IR)拮抗剂苦鬼白醇对体内和体外小鼠植入前胚胎发育的作用。

设计

体内和体外研究。

设置

医院研究单位。

动物

FVB/N 小鼠和小鼠胚胎。

干预措施

苦鬼白醇对体内和体外小鼠胚胎发育的影响,免疫组织化学,酶联免疫吸附试验,聚合酶链反应。

主要观察指标

胚胎发育、IGF-IR 存在、信使 RNA 表达、IGF-I 合成。

结果

苦鬼白醇对胚胎发育的影响在体内和体外均不可逆转。交配后 1 至 3 天接受苦鬼白醇治疗的小鼠囊胚数量减少,分别为 40.5%和 78.8%,发育延迟的胚胎数量更多,分别为 48.6%和 11.5%。胰岛素样生长因子-IR 蛋白在胚胎发育的各个阶段均以磷酸化和非磷酸化形式存在。卵母细胞中相对 IGF-IR 信使 RNA 表达最高,在发育到囊胚阶段时降低。苦鬼白醇处理后培养基中的胰岛素样生长因子-I 减少。

结论

我们得出结论,IGF-I 在正常小鼠胚胎发育中具有重要作用,其受体在胚胎基因组激活过程中发挥重要作用。

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