KSRP蛋白和IL-6在精子发生过程中的功能研究
发布时间：2019-06-05 00:31
【摘要】：在生精小管中进行的精子发生是一个复杂的成长和成熟过程,有许多不同的原因会导致男性生殖细胞发育的失败。随着日益严峻的工作生活压力和环境污染形势,正常育龄夫妇的不孕不育发病率在不断的显著上升。其中,由男性方面因素引起的病例约占50%,而且大多数病因不明。不孕不育症已经成为主要的临床、社会和经济问题。已有研究表明,由于遗传因素异常而引发的生精障碍至少占男性不育的一半以上。因此,进一步的研究男性不育产生的原因及分子机制,有助于提高男性不育的临床诊断和治疗。 支持细胞(Sertoli cell)位于生精小管的基底部,为生殖细胞的发育提供结构上和功能上的支持。血睾屏障(Blood-testis barrier, BTB)由相邻的支持细胞之间形成,为生殖细胞的正常发育提供一个稳定的微环境,是睾丸的天然免疫屏障。在生精周期的第Ⅷ-Ⅺ期,前细线期/细线期的精母细胞会穿过血睾屏障以完成后续的精子发生。血睾屏障的破坏会导致睾丸免疫屏障的破坏,进而引起不育。 之前的研究表明,近来研究表明,一些炎症因子(如：TGF-β3,TNF-a和IL-1)在精子发生过程中可以调控血睾屏障的完整性,以利于前细线期／细线期精母细胞穿过血睾屏障。在睾丸中,IL-6可以抑制在生精上皮周期过程中减数分裂的DNA的合成,降低精子的运动能力,影响支持细胞对transferrin和inhibin B的分泌。在正常大鼠中,IL-6还可以通过阻断MAPK14信号通路而破坏支持细胞紧密连接的通透性。但是,IL-6在调控血睾屏障中的功能却不是很清楚。本论文的第一部分主要是对IL-6在影响血睾屏障动力学方面的分子机制的探讨。我们发现IL-6能够破坏血睾屏障的完整性,改变血睾屏障膜整合蛋白在细胞中的正常定位和表达水平。进一步的研究发现,IL-6可以通过抑制血睾屏障组成蛋白的降解和激活ERK-MAPK信号通路来调控血睾屏障。我们的研究为阐明IL-6在调控血睾屏障完整性的功能研究提供了新的分子机制。 拟染色小体(Chromatoid body, CB),是一种雄性生殖细胞所特有的云状结构。拟染色小体在粗线期精母细胞的细胞质中以位于线粒体簇空隙中的纤维状颗粒结构的形式首次出现,到圆形精细胞时期压缩形成一个单一的、纤维状的核周颗粒,在长形精细胞时期逐渐消失。由于其中含有大量的蛋白质、mRNAs和非编码RNA,拟染色小体被认为是雄性生殖细胞所特有的RNA存储和加工中心。虽然拟染色小体被发现了一百多年,但是其在精子发生过程和男性不育中的具体功能是什么现在还不是很清楚。在小鼠中,拟染色小体的成分敲除后会导致小鼠不育,因此推测拟染色小体可能在精子发生过程和男性不育中发挥重要的功能。 KH-type剪切调控蛋白(KH-type splicing regulatory protein, KSRP)在体细胞中可以调控基因表达和一些特定的microRNAs的成熟。但是KSRP蛋白在精子发生过程和男性不育方面的功能却知之甚少。本论文的第二部分研究,主要是探讨KSRP蛋白在精子发生过程中所起到的功能。我们发现KSRP蛋白在睾丸中是核质蛋白,可以定位在拟染色小体上,是拟染色小体的一种新的组成成分。KSRP蛋白可以通过与拟染色小体蛋白PABP1和PABP2以及拟染色小体中的mRNAs和microRNA的相互作用,进而可能参与到单倍体生殖细胞中mRNAs的翻译和microRNA的加工成熟调控。KSRP蛋白还可以在miRNA-182的介导下完成与拟染色小体蛋白Ddx5的结合,进而参与调控拟染色小体的组织。此外,我们发现在KSRP基因敲除小鼠和寡精症患者的睾丸组织中拟染色小体的组成成分的异常表达。因此,我们的研究结果为理解KSRP蛋白在精子发生和拟染色小体中的功能提供了新的分子机制。
[Abstract]:Spermatogenesis in the seminiferous tubules is a complex growth and maturation process, with many different causes leading to the failure of male germ cell development. With the increasing pressure of working life and environment pollution, the incidence of infertility in the regular and married couples is increasing significantly. Among them, the number of cases due to male factors is about 50%, and most of the causes are unknown. Infertility has become a major clinical, social and economic issue. The research has shown that the spermatogenic disorder caused by the abnormality of the genetic factors at least accounts for more than half of the male infertility. Therefore, a further study of the causes and molecular mechanisms of male infertility can help to improve the clinical diagnosis and treatment of male infertility. The support cell (Sertoli cell) is located at the base of the spermatogenic tubule, providing structural and functional support for the development of the germ cells. The blood-testis barrier (BTB) is formed between adjacent supporting cells, providing a stable microenvironment for the normal development of the germ cells, which is the natural immune screen of the testis. Barrier. The spermatocytes in the pre-fine-line/ fine-line phase will pass through the blood-testis barrier to complete subsequent sperm delivery during the period VIII-1 of the spermatogenic cycle. The destruction of the blood-to-testis barrier can lead to the destruction of the immune barrier of the testis, which in turn causes no damage. The previous studies have shown that recent studies have shown that some inflammatory factors (e.g., TGF-3, TNF-a and IL-1) can regulate the integrity of the blood-testis barrier during spermatogenesis, to facilitate the passage of the pre-fine line/ fine-line spermatocytes through the blood In the testis, IL-6 can inhibit the synthesis of meiosis in the process of spermatogenic epithelium, reduce the motility of the sperm, and affect the support of the cells to transferrin and inhibin B. In normal rats, IL-6 can also destroy the tight junction of the support cells by blocking the MAPK14 signaling pathway. Permeability. However, the function of IL-6 in regulating the blood-testis barrier is not It is clear that the first part of this paper is mainly the molecular mechanism of IL-6 in the dynamics of the blood-testis barrier. We found that IL-6 can destroy the integrity of the blood-testis barrier and change the normal localization of the whole protein of the blood-testis barrier membrane in the cell. Further study found that IL-6 can regulate blood by inhibiting the degradation and activation of the ERK-MAPK signal pathway of the blood-testis barrier component. The testis barrier. Our study provides a new division of the functional study of IL-6 in regulating the integrity of the blood-testis barrier Submechanism. The species of the species to be dyed (CB) is a characteristic of a male germ cell. The structure of the cloud-like structure is the first appearance of the structure of the fibrous structure in the cytoplasm of the spermatocytes of the coarse line, which is located in the space of the mitochondrial cluster, and is compressed to form a single, fibrous, nuclear-like particle in the period of the round sperm cell, and in the case of the long-form fine cell, As a result of the fact that a large amount of protein, mRNAs, and non-coding RNAs, the pseudo-staining bodies are thought to be the specific RNA storage of the male germ cells and the processing center. Although the pseudo-stained body has been found for more than a hundred years, its specific function in the spermatogenesis and male infertility is now It is not clear. In the mouse, the component of the pseudo-stained body is knocked out to cause the mouse to be sterile, so it is presumed that the pseudo-stained body may play a role in the spermatogenesis and in the male infertility. KH-type cleavage regulatory protein (KSRP) can regulate gene expression and specific micro-micro in somatic cells. The maturation of the RNAs, but the KSRP protein is in the process of spermatogenesis and male infertility. Little is known about the function. The second part of this paper is to study the genesis of the KSRP protein in the spermatogenesis. We found that the KSRP protein is a nuclear protein in the testis, can be positioned on the pseudo-stained body, and is the one that is to be dyed. The KSRP protein can be involved in the translation and microRNA of mRNAs in the haploid germ cells by the interaction with the mRNAs and microRNAs in the pseudo-stained body proteins PABP1 and PABP2 and the pseudo-stained bodies. The KSRP protein can also be combined with the pseudo-stained body protein Ddx5 under the mediation of the miRNA-182, and further participate in the regulation and control. The tissue of the stained body. In addition, we found the composition of the bodies to be dyed in the testis of the KSRP gene knockout mice and oligospermia. Therefore, the results of our study are to understand the function of the KSRP protein in the spermatogenesis and the pseudo-stained body.
【学位授予单位】：中国科学技术大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R698.2
本文编号：2493116
[Abstract]:Spermatogenesis in the seminiferous tubules is a complex growth and maturation process, with many different causes leading to the failure of male germ cell development. With the increasing pressure of working life and environment pollution, the incidence of infertility in the regular and married couples is increasing significantly. Among them, the number of cases due to male factors is about 50%, and most of the causes are unknown. Infertility has become a major clinical, social and economic issue. The research has shown that the spermatogenic disorder caused by the abnormality of the genetic factors at least accounts for more than half of the male infertility. Therefore, a further study of the causes and molecular mechanisms of male infertility can help to improve the clinical diagnosis and treatment of male infertility. The support cell (Sertoli cell) is located at the base of the spermatogenic tubule, providing structural and functional support for the development of the germ cells. The blood-testis barrier (BTB) is formed between adjacent supporting cells, providing a stable microenvironment for the normal development of the germ cells, which is the natural immune screen of the testis. Barrier. The spermatocytes in the pre-fine-line/ fine-line phase will pass through the blood-testis barrier to complete subsequent sperm delivery during the period VIII-1 of the spermatogenic cycle. The destruction of the blood-to-testis barrier can lead to the destruction of the immune barrier of the testis, which in turn causes no damage. The previous studies have shown that recent studies have shown that some inflammatory factors (e.g., TGF-3, TNF-a and IL-1) can regulate the integrity of the blood-testis barrier during spermatogenesis, to facilitate the passage of the pre-fine line/ fine-line spermatocytes through the blood In the testis, IL-6 can inhibit the synthesis of meiosis in the process of spermatogenic epithelium, reduce the motility of the sperm, and affect the support of the cells to transferrin and inhibin B. In normal rats, IL-6 can also destroy the tight junction of the support cells by blocking the MAPK14 signaling pathway. Permeability. However, the function of IL-6 in regulating the blood-testis barrier is not It is clear that the first part of this paper is mainly the molecular mechanism of IL-6 in the dynamics of the blood-testis barrier. We found that IL-6 can destroy the integrity of the blood-testis barrier and change the normal localization of the whole protein of the blood-testis barrier membrane in the cell. Further study found that IL-6 can regulate blood by inhibiting the degradation and activation of the ERK-MAPK signal pathway of the blood-testis barrier component. The testis barrier. Our study provides a new division of the functional study of IL-6 in regulating the integrity of the blood-testis barrier Submechanism. The species of the species to be dyed (CB) is a characteristic of a male germ cell. The structure of the cloud-like structure is the first appearance of the structure of the fibrous structure in the cytoplasm of the spermatocytes of the coarse line, which is located in the space of the mitochondrial cluster, and is compressed to form a single, fibrous, nuclear-like particle in the period of the round sperm cell, and in the case of the long-form fine cell, As a result of the fact that a large amount of protein, mRNAs, and non-coding RNAs, the pseudo-staining bodies are thought to be the specific RNA storage of the male germ cells and the processing center. Although the pseudo-stained body has been found for more than a hundred years, its specific function in the spermatogenesis and male infertility is now It is not clear. In the mouse, the component of the pseudo-stained body is knocked out to cause the mouse to be sterile, so it is presumed that the pseudo-stained body may play a role in the spermatogenesis and in the male infertility. KH-type cleavage regulatory protein (KSRP) can regulate gene expression and specific micro-micro in somatic cells. The maturation of the RNAs, but the KSRP protein is in the process of spermatogenesis and male infertility. Little is known about the function. The second part of this paper is to study the genesis of the KSRP protein in the spermatogenesis. We found that the KSRP protein is a nuclear protein in the testis, can be positioned on the pseudo-stained body, and is the one that is to be dyed. The KSRP protein can be involved in the translation and microRNA of mRNAs in the haploid germ cells by the interaction with the mRNAs and microRNAs in the pseudo-stained body proteins PABP1 and PABP2 and the pseudo-stained bodies. The KSRP protein can also be combined with the pseudo-stained body protein Ddx5 under the mediation of the miRNA-182, and further participate in the regulation and control. The tissue of the stained body. In addition, we found the composition of the bodies to be dyed in the testis of the KSRP gene knockout mice and oligospermia. Therefore, the results of our study are to understand the function of the KSRP protein in the spermatogenesis and the pseudo-stained body.
【学位授予单位】：中国科学技术大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R698.2
【参考文献】
相关期刊论文 前2条
1 欧建平;抗精子抗体对辅助生育的影响[J];中华男科学;2003年03期
2 ;Interleukin-6, desmosome and tight junction protein expression levels in reflux esophagitis-affected mucosa[J];World Journal of Gastroenterology;2009年29期
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