Interactions between progesterone and tumor necrosis factor-α in the regulation of primordial follicle assembly
Interactions between progesterone and tumor necrosis factor-α in the regulation of primordial follicle assembly
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DOI：
10.1530/rep-06-0045
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发表时间：
2006-12-01
期刊：
影响因子：
3.8
通讯作者：
Skinner, Michael K.
中科院分区：
文献类型：
--
作者：
Nilsson, Eric E.;Stanfield, Jacob;Skinner, Michael K.
卵泡组装是卵细胞群或卵巢分解形成原始卵泡的过程。原始卵泡池的大小是决定雌性生殖寿命的主要因素。先前，黄体酮（P-4）已被证明可抑制卵泡组装，而肿瘤坏死因子- α (TNF α)已被证明可促进卵泡组装所必需的细胞凋亡。本研究探讨TNFa和黄体酮如何相互作用，以调节原始卵泡组装。取新生大鼠卵巢进行器官培养，观察P-4和TNF α的作用。在体外和体内均发现P-4可减少原始卵泡的组装，增加未组装卵母细胞的百分比。TNFa处理没有改变培养卵巢中组装卵泡的比例，但阻断了P4抑制卵泡组装的能力。卵巢转录组的微阵列分析显示，黄体酮处理改变了513个基因的表达，其中132个仅在P4处理后表达，16个仅在对照卵巢中表达。大多数基因比对照组上调两倍以上，16个基因的一小部分下调。受P4影响的基因类别包括一组细胞外信号因子。卵泡组装时表达的孕激素受体包括表面膜孕激素受体PGRMC1、PGRMC2和RDA288。核基因组P-4受体未明显表达。孕酮增加了几种基因（TANK、NF κ B、Bcl2l1和Bcl2l2）的表达，这些基因参与促进细胞存活和抑制细胞凋亡的信号通路。观察结果表明，P-4通过表面膜孕酮受体调节原始卵泡的组装，TNF α可以超越P-4对卵泡组装的抑制作用。参与P-4作用的主要机制是细胞存活基因的增加和细胞凋亡途径的抑制。观察结果提供了对原始卵泡组装的激素调节的见解，并导致潜在操纵卵泡组装和生殖能力的新方法。
Follicle assembly is the process by which groups or 'nests' of oocytes break down to form primordial follicles. The size of the primordial follicle pool is the major determinant of the reproductive lifespan of a female. Previously, progesterone (P-4) has been shown to inhibit follicle assembly, while tumor necrosis factor-alpha (TNF alpha) has been shown to promote the apoptosis that is necessary for follicle assembly. The present study examines how TNFa and progesterone interact to regulate primordial follicle assembly. Ovaries were collected from newborn rats and placed in organ culture to examine the actions of P-4 and TNF alpha. P-4 was found to decrease primordial follicle assembly and increase the percentage of unassembled oocytes both in vitro and in vivo. TNFa treatment did not change the proportion of assembled follicles in cultured ovaries, but blocked the ability Of P4 to inhibit follicle assembly. Microarray analysis of the ovarian transcriptome revealed that progesterone treatment of the ovaries altered the expression of 513 genes with 132 only expressed after P4 treatment and 16 only expressed in control ovaries. The majority ofgenes were up-regulated greater than twofold over control, with a small subset of 16 genes down-regulated. Categories of genes affected by P4 are described including a group of extracellular signaling factors. The progesterone receptors expressed at the time of follicle assembly included the surface membrane progesterone receptors PGRMC1, PGRMC2, and RDA288. The nuclear genomic P-4 receptor was not expressed at appreciable levels. Progesterone increased the expression of several genes (TANK, NF kappa B, Bcl2l1, and Bcl2l2) involved in a signaling pathway that promotes cell survival and inhibits apoptosis. Observations indicate that P-4 acts through the surface membrane progesterone receptors to regulate primordial follicle assembly, and that TNF alpha can override the inhibitory actions of P-4 on follicle assembly. A major mechanism involved in the actions of P-4 is an increase in cell survival genes and inhibition of the apoptosis pathway. Observations provide insight into the hormonal regulation of primordial follicle assembly and lead to novel approaches to potentially manipulate follicle assembly and reproductive capacity.