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患有卵巢囊肿疾病奶牛的卵泡中胰岛素信号通路受损。

Impaired insulin signaling pathway in ovarian follicles of cows with cystic ovarian disease.

作者信息

Hein G J, Panzani C G, Rodríguez F M, Salvetti N R, Díaz P U, Gareis N C, Benítez G A, Ortega H H, Rey F

机构信息

Laboratorio de Biología Celular y Molecular Aplicada, Facultad de Ciencias Veterinarias, Universidad Nacional del Litoral, Argentina; Instituto de Ciencias Veterinarias del Litoral (ICIVET Litoral), Consejo Nacional de Investigaciones Científicas y Tecnológicas, (CONICET), Argentina.

Laboratorio de Biología Celular y Molecular Aplicada, Facultad de Ciencias Veterinarias, Universidad Nacional del Litoral, Argentina; Instituto de Ciencias Veterinarias del Litoral (ICIVET Litoral), Consejo Nacional de Investigaciones Científicas y Tecnológicas, (CONICET), Argentina.

出版信息

Anim Reprod Sci. 2015 May;156:64-74. doi: 10.1016/j.anireprosci.2015.02.010. Epub 2015 Mar 9.

DOI:10.1016/j.anireprosci.2015.02.010
PMID:25813700
Abstract

Cystic ovarian disease (COD) is an important cause of infertility in dairy cattle. Follicular cell steroidogenesis and proliferation in ovulatory follicles is stimulated by hormones such as insulin and its necessary post-receptor response. The aim of this study was to determine the expression of insulin receptor (IR), IR substrate-1 (IRS1) and phosphatidylinositol 3-kinase (PI3K), key intermediates in the insulin pathway, in control cows and cows with spontaneous COD and ACTH-induced COD. IR and IRS1 mRNA levels were greater in granulosa cells and lower in follicular cysts than in control tertiary follicles. PI3K mRNA levels were similar in all follicles evaluated, whereas the expression of IR, IRS1 and PI3K was similar in theca cells. Protein expression of IR was higher in control tertiary follicles than in the same structures in animals with COD and with cysts. IRS1 and PI3K protein expression showed the same pattern in tertiary and cystic follicles. However, the protein expression of subunit alpha p85 of PI3K was greater in theca cells from tertiary follicles than in cystic follicles. These results provide new insights into the insulin response in cows with COD. The lower gene and protein expressions of some insulin downstream effectors at an early stage of the signaling pathway could negatively influence the functionality of ovaries and contribute to follicle persistence.

摘要

卵巢囊肿疾病(COD)是奶牛不孕的一个重要原因。胰岛素等激素及其必要的受体后反应可刺激排卵卵泡中的卵泡细胞类固醇生成和增殖。本研究的目的是确定胰岛素途径中的关键中间体胰岛素受体(IR)、胰岛素受体底物-1(IRS1)和磷脂酰肌醇3-激酶(PI3K)在对照奶牛以及患有自发性COD和促肾上腺皮质激素诱导的COD的奶牛中的表达情况。颗粒细胞中IR和IRS1的mRNA水平高于对照三级卵泡,而卵泡囊肿中的则低于对照三级卵泡。在所有评估的卵泡中,PI3K的mRNA水平相似,而在卵泡膜细胞中,IR、IRS1和PI3K的表达相似。对照三级卵泡中IR的蛋白表达高于患有COD和囊肿的动物相同结构中的表达。IRS1和PI3K的蛋白表达在三级卵泡和囊性卵泡中呈现相同模式。然而,PI3K亚基α p85的蛋白表达在三级卵泡的卵泡膜细胞中高于囊性卵泡。这些结果为患有COD的奶牛的胰岛素反应提供了新的见解。信号通路早期一些胰岛素下游效应器较低的基因和蛋白表达可能会对卵巢功能产生负面影响,并导致卵泡持续存在。

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