Transcriptome profiling of granulosa cells of bovine ovarian follicles during growth from small to large antral sizes.
Transcriptome profiling of granulosa cells of bovine ovarian follicles during growth from small to large antral sizes.
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DOI：
10.1186/1471-2164-15-24
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发表时间：
2014-01-14
期刊：
影响因子：
4.4
通讯作者：
Rodgers RJ
中科院分区：
文献类型：
--
作者：
Hatzirodos N;Irving-Rodgers HF;Hummitzsch K;Harland ML;Morris SE;Rodgers RJ
在卵泡发生的后期，哺乳动物的卵泡含有围绕窦腔的上皮颗粒细胞层。在卵泡发育过程中，颗粒细胞进行复制，分泌激素并支持卵母细胞的生长。在牛中，卵泡需要生长直径> 10 mm以允许卵母细胞排卵，随后颗粒细胞停止分裂并分化为黄体的特化细胞。为了更好地理解卵泡生长和颗粒细胞成熟的分子基础，我们使用Affyrons微阵列（24，128个探针组）对来自小（< 5 mm; n = 10）和大（> 10 mm，n = 4）健康牛卵泡的颗粒细胞进行转录组分析。对前两个成分进行主成分分析和系统聚类，结果表明，聚类分为两个组，小和大，前者是更异质性。每个探针组的信号强度的变异系数的大小-频率分布也显示，小卵泡比大卵泡更不均匀。IPA和GO富集分析显示，轴突导向，免疫信号传导和细胞重排的过程中受到最大的影响，在大卵泡。最重要的网络与：（A）Notch、SLIT/ROBO和PI 3 K信号传导，和（B）ITGB 5和通过细胞外信号相关激酶（ERK）的细胞外基质信号传导相关。预计在大卵泡中活跃的上游调节基因包括STAT和XBP 1。相比之下，发育过程，如刺激的KIT，IHH和MEST是最活跃的小卵泡。MGEA 5被鉴定为小卵泡的上游调节因子。它编码一种酶，通过从丝氨酸和苏氨酸残基中去除N-乙酰葡糖胺来改变许多靶蛋白的活性，包括参与能量传感的那些。我们的数据表明，随着卵泡扩大，更多的基因和/或途径被激活，而不是失活，基因表达变得更加均匀。这些发现可以解释为大卵泡中的细胞在其基因表达方面更均匀，或者卵泡更均匀，或者两者的组合，以及其他因素，如LH，另外控制颗粒细胞。
At later stages of folliculogenesis, the mammalian ovarian follicle contains layers of epithelial granulosa cells surrounding an antral cavity. During follicle development granulosa cells replicate, secrete hormones and support the growth of the oocyte. In cattle, the follicle needs to grow > 10 mm in diameter to allow an oocyte to ovulate, following which the granulosa cells cease dividing and differentiate into the specialised cells of the corpus luteum. To better understand the molecular basis of follicular growth and granulosa cell maturation, we undertook transcriptome profiling of granulosa cells from small (< 5 mm; n = 10) and large (> 10 mm, n = 4) healthy bovine follicles using Affymetrix microarrays (24,128 probe sets). Principal component analysis for the first two components and hierarchical clustering showed clustering into two groups, small and large, with the former being more heterogeneous. Size-frequency distributions of the coefficient of variation of the signal intensities of each probe set also revealed that small follicles were more heterogeneous than the large. IPA and GO enrichment analyses revealed that processes of axonal guidance, immune signalling and cell rearrangement were most affected in large follicles. The most important networks were associated with: (A) Notch, SLIT/ROBO and PI3K signalling, and (B) ITGB5 and extracellular matrix signalling through extracellular signal related kinases (ERKs). Upstream regulator genes which were predicted to be active in large follicles included STAT and XBP1. By comparison, developmental processes such as those stimulated by KIT, IHH and MEST were most active in small follicles. MGEA5 was identified as an upstream regulator in small follicles. It encodes an enzyme that modifies the activity of many target proteins, including those involved in energy sensing, by removal of N-acetylglucosamine from serine and threonine residues. Our data suggest that as follicles enlarge more genes and/or pathways are activated than are inactivated, and gene expression becomes more uniform. These findings could be interpreted that either the cells in large follicles are more uniform in their gene expression, or that follicles are more uniform or a combination of both and that additional factors, such as LH, are additionally controlling the granulosa cells.
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