無精子癥患者的減數(shù)分裂研究
發(fā)布時(shí)間：2018-07-29 18:32
【摘要】：哺乳動(dòng)物精子發(fā)生是一個(gè)受到嚴(yán)格調(diào)控的復(fù)雜過程,在減數(shù)分裂前期Ⅰ,同源染色體的重組將同源染色體聯(lián)系在一起,從而保證了減數(shù)分裂后期Ⅰ染色體的正確分離。本研究探究了減數(shù)分裂染色體配對、聯(lián)會(huì)和重組的異常對男性精子發(fā)生的影響： 第一,染色體相互易位是一種常見的染色體結(jié)構(gòu)異常,通常會(huì)導(dǎo)致男性不育,但具體機(jī)制仍不太清楚。本文利用精母細(xì)胞鋪展和免疫熒光染色,對3例染色體核型分別為46,XY,t(8;15),46)X,t(Y;l)(p11.3;p31)和46,XY,t(5;7;9;13)(5q11;7p11;7P15;9q12;13p12)的無精子癥患者進(jìn)行了減數(shù)分裂進(jìn)程、配對、聯(lián)會(huì)以及重組的研究。發(fā)現(xiàn)與正常人相比,染色體易位患者減數(shù)分裂進(jìn)程受到明顯的影響,γH2AX和BRCA1定位于易位染色體不聯(lián)會(huì)的區(qū)域,性染色體的遺傳重組頻率降低,易位的染色體和未涉及易位的染色體上的遺傳重組也受到影響。這些減數(shù)分裂異常的細(xì)胞凋亡明顯增加,可能因此導(dǎo)致了染色體易位攜帶者的精子發(fā)生障礙和不育。 第二,雖然大多數(shù)47,XYY的男性可育,但也有部分患者表現(xiàn)為精子數(shù)目減少乃至無精子。本文利用免疫熒光染色,對2例染色體核型分別為48,XYY,+sSMC和47,XYY的無精子癥患者的減數(shù)分裂進(jìn)行了研究。與正常人相比,XYY患者的減數(shù)分裂進(jìn)程受到明顯影響,48,XYY,+sSMC患者性染色體的遺傳重組頻率明顯降低,47,XYY患者出現(xiàn)了不同的性染色體構(gòu)型,重組不僅發(fā)生在Y染色體的短臂上,在Y染色體的長臂上也觀察到了重組。與常染色體的染色相似,在兩條Y染色體已配對聯(lián)會(huì)的區(qū)域也沒有γH2AX信號。這些結(jié)果表明,精母細(xì)胞中額外的Y染色體干擾了減數(shù)分裂,從而導(dǎo)致了XYY患者精子發(fā)生異常和不育。 第三,減數(shù)分裂同源染色體聯(lián)會(huì)異常可導(dǎo)致精子發(fā)生停滯,進(jìn)而引起男性不育。本文利用免疫熒光染色等,對無精子癥患者的睪丸活檢組織進(jìn)行了減數(shù)分裂進(jìn)程、同源染色體配對、聯(lián)會(huì)以及重組進(jìn)行了研究。發(fā)現(xiàn)部分患者的所有細(xì)胞都表現(xiàn)出染色體配對聯(lián)會(huì)異常,減數(shù)分裂停滯在粗線期。但也有一些患者,僅部分精母細(xì)胞表現(xiàn)為聯(lián)會(huì)異常。這些結(jié)果表明,染色體聯(lián)會(huì)異常是導(dǎo)致男性不育的一個(gè)重要因素,但不是唯一因素。
[Abstract]:Mammalian spermatogenesis is a complex process under strict regulation. In meiotic Prophase I, homologous chromosomes are linked by recombination of homologous chromosomes, thus ensuring the correct separation of chromosomes I in meiotic anaphase. This study explored the effects of meiotic chromosomal pairing, synaptic and recombination abnormalities on male spermatogenesis: first, chromosomal translocation is a common chromosomal structural abnormality that usually leads to male infertility. But the exact mechanism remains unclear. By means of spermatocyte spreading and immunofluorescence staining, the meiosis process, pairing, synapsis and recombination of three cases of azoospermia with chromosome karyotypes 46 (46) XYT (p11.3p31) and 46 XYT (5q117p117P159q1213p12) were studied by means of spermatocyte spreading and immunofluorescence staining. It was found that the process of meiosis in patients with chromosome translocation was significantly affected compared with that in normal subjects. 緯 H2AX and BRCA1 were located in the regions of chromosomal disjunction of translocation, and the frequency of genetic recombination of sex chromosomes was decreased. Genetic recombination on translocation chromosomes and chromosomes not involved in translocation is also affected. These abnormal meiosis increased apoptosis, which may lead to sperm dysfunction and infertility in chromosome translocation carriers. Second, while most of the 47 XYY males were fertile, some patients showed decreased sperm count and even azoospermia. The meiosis of two cases of azoospermia with chromosome karyotypes of 48 XYY, sSMC and 47 XYY were studied by immunofluorescence staining. The process of meiosis in XYY patients was significantly affected compared with that in normal controls. The frequency of genetic recombination of sex chromosomes in sSMC patients was significantly lower than that in normal controls. Different sexual chromosomal configurations appeared in patients with XYY. The recombination occurred not only on the short arm of Y chromosome, but also on the short arm of Y chromosome. Recombination was also observed on the long arm of the Y chromosome. Similar to autosomal staining, there is no 緯 H2AX signal in the region where the two Y chromosomes have paired synapses. These results suggest that the extra Y chromosome in spermatocytes interferes with meiosis, resulting in abnormal spermatozoa and infertility in XYY patients. Third, abnormal meiotic homologous chromosomal synapsis may lead to sperm stagnation, which can lead to male infertility. The process of meiosis homologous chromosome pairing synapsis and recombination of testicular biopsy tissues in azoospermia patients were studied by immunofluorescence staining. It was found that all the cells in some patients showed chromosomal pairing synaptic abnormalities and meiosis stagnated in the coarse-line phase. However, in some patients, only some spermatocytes showed synaptic abnormalities. These results suggest that chromosomal abnormalities are an important, but not the only, cause of male infertility.
【學(xué)位授予單位】：中國科學(xué)技術(shù)大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2015
【分類號】：R698.2
本文編號：2153622
[Abstract]:Mammalian spermatogenesis is a complex process under strict regulation. In meiotic Prophase I, homologous chromosomes are linked by recombination of homologous chromosomes, thus ensuring the correct separation of chromosomes I in meiotic anaphase. This study explored the effects of meiotic chromosomal pairing, synaptic and recombination abnormalities on male spermatogenesis: first, chromosomal translocation is a common chromosomal structural abnormality that usually leads to male infertility. But the exact mechanism remains unclear. By means of spermatocyte spreading and immunofluorescence staining, the meiosis process, pairing, synapsis and recombination of three cases of azoospermia with chromosome karyotypes 46 (46) XYT (p11.3p31) and 46 XYT (5q117p117P159q1213p12) were studied by means of spermatocyte spreading and immunofluorescence staining. It was found that the process of meiosis in patients with chromosome translocation was significantly affected compared with that in normal subjects. 緯 H2AX and BRCA1 were located in the regions of chromosomal disjunction of translocation, and the frequency of genetic recombination of sex chromosomes was decreased. Genetic recombination on translocation chromosomes and chromosomes not involved in translocation is also affected. These abnormal meiosis increased apoptosis, which may lead to sperm dysfunction and infertility in chromosome translocation carriers. Second, while most of the 47 XYY males were fertile, some patients showed decreased sperm count and even azoospermia. The meiosis of two cases of azoospermia with chromosome karyotypes of 48 XYY, sSMC and 47 XYY were studied by immunofluorescence staining. The process of meiosis in XYY patients was significantly affected compared with that in normal controls. The frequency of genetic recombination of sex chromosomes in sSMC patients was significantly lower than that in normal controls. Different sexual chromosomal configurations appeared in patients with XYY. The recombination occurred not only on the short arm of Y chromosome, but also on the short arm of Y chromosome. Recombination was also observed on the long arm of the Y chromosome. Similar to autosomal staining, there is no 緯 H2AX signal in the region where the two Y chromosomes have paired synapses. These results suggest that the extra Y chromosome in spermatocytes interferes with meiosis, resulting in abnormal spermatozoa and infertility in XYY patients. Third, abnormal meiotic homologous chromosomal synapsis may lead to sperm stagnation, which can lead to male infertility. The process of meiosis homologous chromosome pairing synapsis and recombination of testicular biopsy tissues in azoospermia patients were studied by immunofluorescence staining. It was found that all the cells in some patients showed chromosomal pairing synaptic abnormalities and meiosis stagnated in the coarse-line phase. However, in some patients, only some spermatocytes showed synaptic abnormalities. These results suggest that chromosomal abnormalities are an important, but not the only, cause of male infertility.
【學(xué)位授予單位】：中國科學(xué)技術(shù)大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2015
【分類號】：R698.2
【參考文獻(xiàn)】
相關(guān)期刊論文 前2條
1 ZaidaSarrate;JoanBlanco;EsterAnton;SusanaEgozcue;JosepEgozcue;FrancescaVidal;;FISH studies of chromosome abnormalities in germ cells and its relevance in reproductive counseling[J];Asian Journal of Andrology;2005年03期
2 Hanwei Jiang;Liu Wang;Yingxia Cui;Zhipeng Xu;Tonghang Guo;Dongkai Cheng;Peng Xu;Wen Yu;Qinghua Shi;;Meiotic Chromosome Behavior in a Human Male t(8;15)Carrier[J];Journal of Genetics and Genomics;2014年03期
，本文編號：2153622
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