Thrombospondin and vascular endothelial growth factor are cyclically expressed in an inverse pattern during bovine ovarian follicle development

Thrombospondin and vascular endothelial growth factor are cyclically expressed in an inverse pattern during bovine ovarian follicle development
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DOI:
10.1095/biolreprod.104.031120
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发表时间:
2005-05-01
影响因子:
3.6
通讯作者:
Petrik, JJ
Petrik, JJ
中科院分区:
生物学2区
文献类型:
--
作者:
Greenaway, J;Gentry, PA;Petrik, JJ

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血管生成通常不会发生在大多数成人组织中。然而,在卵巢中,存在周期性血管变化,包括涉及许多细胞因子和生长因子相互作用的血管生成。血管生成过程受促血管生成因子和抗血管生成因子之间的平衡调节。本研究的目的是确定抗血管生成的血小板反应蛋白家族和促血管生成的血管内皮生长因子(VEGF)在各种大小的健康牛卵泡的表达。从屠宰场动物收集卵巢,并基于大小(<0.5cm,小; 0.5- 1.0cm,中等; > 1.0cm,大)分选健康卵泡。血小板反应蛋白(TSP)蛋白水平显着较高的小卵泡。免疫组化证实颗粒层是卵泡内参与TSP生成的主要区域,小卵泡中免疫阳性细胞比例最高。TSP-1和-2 mRNA水平在小卵泡中显著高于中等或大卵泡。TSP与CD 36共定位于卵泡和培养细胞中的颗粒细胞(GC)上。与TSP相比,VEGF表达在卵泡生长发育过程中增加。FSH刺激TSP的GC表达,而LH没有影响。综上所述,TSP-1和-2在卵泡发育早期卵巢血管外区室协调表达。VEGF呈负向表达,随着卵泡的发育表达增加。这些蛋白质的表达和定位的调节表明,它们可能以一种新的方式参与调节卵泡的生长和发育。
Angiogenesis does not normally occur in most adult tissues. However, in the ovary, there are cyclical vascular changes including angiogenesis that involve the interaction of numerous cytokines and growth factors. Angiogenic processes are regulated by a balance between pro- and antiangiogenic factors. The purpose of this study was to determine the expression of the antiangiogenic thrombospondin family and proangiogenic vascular endothelial growth factor (VEGF) in various sizes of healthy bovine follicles. Ovaries were collected from slaughterhouse animals and healthy follicles were sorted based on size (< 0.5 cm, small; 0.5-1.0 cm, medium; > 1.0 cm, large). Thrombospondin (TSP) protein levels were significantly higher in small follicles. Immunohistochemistry confirmed the granulosa layer as the primary area within the follicle involved in TSP generation and that small follicles had the highest proportion of immunopositive cells. TSP-1 and -2 mRNA levels were significantly higher in small follicles than either medium or large follicles. TSP colocalized with CD36 on granulosa cells (GC) in the follicle and in cultured cells. In contrast with TSP, VEGF expression increased during growth and development of the follicle. FSH stimulated GC expression of TSP, while LH had no effect. In summary, TSP-1 and -2 were coordinately expressed in the extravascular compartment of the ovary during early follicle development. VEGF was inversely expressed, with expression increasing as follicles developed. Regulated expression and localization of these proteins suggests that they may he involved in regulating growth and development of the follicle in a novel fashion.