雄激素与精子发生的关系

雄激素被认为在精子发生中具有重要作用.近年的动物实验以及临床研究提示,雄激素可以导致严重少精子或者无精子症,内源性睾酮可以引起生精细胞凋亡,与生精细胞阻滞高度相关.本文对近年的材料进行分析后,认为雄激素与精子发生的关系在于,雄激素可以引起生精细胞凋亡,造成细胞重排,对精子发生起到调节作用.     

激素对精子发生的调控

精子发生是一个连续不断的细胞增生与分化的过程 ,是激素依赖的调控 ,其中卵泡刺激素 (FSH)和黄体生成素 (LH)刺激释放的睾酮 (T)是主要的激素调节者。睾丸内T是维持精子发生最关健的因素之一 ,而FSH对正常精子发生的起始和维持同样是必须的。在介导激素调节中 ,Sertoli细胞处于核心地位。同时 ,正常精子发生过程中的生精细胞凋亡也是激素调控的。深入研究精子发生的激素调控 ,为探索安全、可复的男性避孕方法奠定了基础。     

睾丸支持细胞和间质细胞在生精细胞凋亡中的作用

睾丸精子发生过程中存在生精细胞凋亡，支持细胞和间质细胞作为非生殖细胞对生精细胞凋亡具有重要作用，本文对这方面的研究作一综述。     

睾丸支持细胞和间质细胞在生精细胞凋亡中的作用

睾丸精子发生过程中存在生精细胞凋亡，支持细胞和间质细胞作为非生殖细胞对生精细胞凋亡具有重要作用。本文对这方面的研究作一综述。     

生精障碍相关基因单核苷酸多态性研究进展

生精相关基因遗传多态性是生精障碍的一个重要的遗传病因.通过基因敲除技术现已鉴定出大量与精子发生密切相关基因.此类生精障碍基因包括表达酶类、受体类、细胞凋亡类、转录调控类等基因.上述基因的遗传易感性、感染和环境等因素共同作用导致男性非梗阻性无精子症和少精子症.生精障碍相关基因单核苷酸多态性(SNP)分析可从分子水平上阐述...     

输精管结扎诱发生精细胞凋亡的研究进展

生精过程是一个精细的调节过程 ,近年生精细胞凋亡的研究进展非常迅速。输精管结扎作为一种刺激因素影响生精细胞凋亡 ,研究表明输精管结扎可使生精细胞凋亡增多。输精管结扎诱导生精细胞凋亡的机制与输精管压力增高、NO作用的影响、基因调控及睾酮水平等有关。本文综述了近年对输精管结扎诱发生精细胞凋亡的研究 ,这对未来男性生殖系统更深入的研究有重要作用     

睾丸支持细胞与生精细胞凋亡的关系

生精细胞处于支持细胞构造的环境中 ,激素、生长因子和温度以及它们与支持细胞的联系调控着生精细胞的分化与成熟 ;细胞之间的旁分泌信号转导亦调节着生精细胞凋亡的过程。在睾丸生精细胞发生的自发性凋亡和诱发性凋亡中 ,支持细胞表达和分泌的产物扮演重要角色。     

微小核糖核酸与雄性生殖

精子发生是一个独特的细胞分化过程,涉及一系列复杂的转录后表达调控。微小核糖核酸(miRNA)是一类非编码RNA,在转录后表达调控中发挥重要作用。在精子发生过程中miRNA的表达具有细胞特异性,并且参与睾丸生殖细胞的成熟和分化。睾丸生精功能障碍时,miRNA的特异变化能够在精浆中体现,可作为男性不育新的诊断标志物。对这些miRNA的研究可以为精子发生和睾丸生精功能障碍的分子机制研究提供一个新的方向。Email:hanxd@nju.edu.cn     

人类凋亡生精细胞超微结构研究

目的 :研究人类生精细胞凋亡的超微结构特征。　方法 :10例不育男性 ,年龄 2 8～ 36岁 ,手淫留取精液标本 ,生理盐水洗涤离心 ,戊二醛固定 ,树脂包埋 ,超薄切片 ,电镜观察。　结果 :①生精细胞及精子存在多形态的超微结构异常 ;②生精细胞凋亡的发生是一连续过程 ,电镜下根据其形态变化可分为 3个阶段 :即凋亡发生的初始阶段 ,首先出现生精细胞核染色质浓缩 ,电子密度高 ,核膜间隙宽 ,局部核膜下或核双层膜间形成空泡 (出芽 ) ;第 2阶段出现核膜膨胀折叠 ,互相融合形成花环状结构 ;第 3阶段表现核膜、胞核裂解 ,细胞形成凋亡小体和残余体 ;③精子凋亡表现为顶体结构异常 ,浆内形成空泡 ,细胞器部分或全部消失 ,胞核浓缩呈细杆状 ,体积缩小 ,核周缘电子密度减低 ;④组织细胞、粒细胞吞噬凋亡的生精细胞或精子并形成髓鞘样结构。　结论 :①生精细胞和精子发生凋亡是男性不育病人常见的异常现象 ;②生精细胞凋亡早期胞核的“出芽”方式有 2种 :即核膜下和核膜间形成囊泡 ,在这过程中 ,核表面先出现针状突起 ,然后转变为光滑 ;③凋亡的生精细胞或精子最后被组织细胞或粒细胞吞噬 ;④对不育男性精液电镜检查 ,了解生精细胞的亚微结构 ,对该病的诊断和治疗具有重要价值。     

支持细胞糖代谢在精子发生中的作用及调控机制的研究进展

睾丸是一种自然缺氧器官,支持细胞糖酵解产生的乳酸是睾丸中生精细胞的重要能量来源,可快速提供ATP,以满足快速增殖的生精细胞对于能量和物质的需求,正常精子发生过程中能量代谢及调控机制的研究受到了广泛关注。因此,阐明不同因素或者疾病状态下调控支持细胞葡萄糖转运蛋白对葡萄糖的转运过程;乳酸脱氢酶将丙酮酸催化为乳酸的过程;单羧酸转运蛋白对乳酸的转运过程,对保证精子发生和雄性生殖功能的正常进行起着至关重要的作用。本文总结了不同生理状态下精子发生过程中能量代谢供求关系及其变化规律,并深入阐述了内分泌因素、信号通路、miRNA和蛋白质乙酰化修饰在调控细胞糖酵解进程中的作用机制,为后续深入阐明精子发生的分子机制和临床诊疗提供重要参考。     

Cytokines produced by microwave-radiated Sertoli cells interfere with spermatogenesis in rat testis

Microwave radiation resulted in degeneration, apoptosis or necrosis in germ cells at different stages. The molecular mechanisms by which microwaves induce spermatogenesis disorder have not been completely understood. Sertoli cells play crucial roles in mammalian spermatogenesis. Cytokines produced by Sertoli cells play pleiotropic roles in different conditions. At physiologically low concentration, TNFα, IL-1β and IL-6 behave as survival factors; while under pathological condition, these cytokines can induce apoptosis in testis. The effects of cytokines produced by microwave-radiated Sertoli cells on spermatogenesis are poorly understood. The purpose of this study was to determine the effect of cytokines produced by microwave-radiated Sertoli cells on the germ cells. We focused the effect of TNFα, IL-1β and IL-6 on the germ cells. The results showed that TNFα, IL-1β and IL-6 were increased in Sertoli cells after exposure to microwave radiation. These up-regulated cytokines can induce apoptosis and lipid peroxidation in the membrane of germ cells. In addition, germ cell apoptosis was associated with the up-regulation of Bax/Bcl-2 and caspase-3. These results suggest that cytokines produced by microwave-radiated Sertoli cells may disrupt spermatogenesis. Our data provided novel insight into the injury mechanism of germ cells induced by microwave radiation.     

Control of spermatogenesis in primate and prospect of male contraception

The present review is a summary of mechanisms of spermatogenesis in primates with emphasis on anti-spermatogenesis of testosterone (T), gossypol, and "testicular heat stress" for development of male contraception, Both FSH and testosterone stimulate all phases of spermatogenesis. FSH is capable of amplifying the population of the differential spermatogonia (B1, B2, B3 and B4) and controls the spermatogonia production rate, and, in synergy with testosterone, regulating spermatogenesis in adult monkeys. Pituitary FSH beta gene expression is governed by a feedback of Beta inhibin, which is a major component of the testicular negative feedback signals. Beta inhibin secreted by Sertoli cells is in turn inhibited by testosterone from Leydig cells under the control of LH. Disturbance of the normal interaction of pituitary FSH with Sertoli cell Beta inhibin is responsible for azoospermia or oligozoospermia induced by exogenous T. Three possible regimens of T, gossypol and "heat stress" have been suggested for male contraception. They act on different sites and stages of spermatogenesis in testis or sperm activity in epididymis. Apoptosis induced by testosterone occurs mainly at staged VII-VIII of spermatogenesis while that by testicular "heat stress" mostly occurs at stages I-IV and X-XII. Low dose of gossypol mainly influences the sperm activity in the epididymis although it also acts on testicular spermatids.     

精原细胞移植的发展与现状

精原细胞移植 (ST)的原理与其他器官移植类似 ,主要通过显微外科技术 ,将供体精原细胞注入受体 ,利用受体微环境使供体细胞分裂分化为精子。根据供体类型以及实验目的 ,将ST分类。其中 ,同种间细胞移植已经获得成功 ,而异种移植 (以人、马、牛、大鼠等为供体 ,免疫缺陷小鼠为受体 )、冰冻细胞移植均未成功 ,其原因可能与免疫排斥反应有关。ST有利于 :①精子发生过程的研究 ,②男性不育症的研究 ,③转基因动物的研究     

Ectopic porcine spermatogenesis in murine subcutis： tissue grafting versus cell-injection methods

Fragments of testis tissue from immature animals grow subcutaneous areas of immunodeficient mice. The same results testes of rodents are injected into the subcutis of nude mice. and develop spermatogenesis when grafted onto are obtained when dissociated cells from immature Those cells reconstitute seminiferous tubules and facilitate spermatogenesis. We compared these two methods, tissue grafting and cell-injection methods, in terms of the efficiency of spermatogenesis in the backs of three strains of immunodeficient mice, using neonatal porcine testicular tissues and cells as donor material. Nude, severe combined immunodeficient （SCID） and NOD/Shi- SCID, IL-2Rγc^null （NOG） mice were used as recipients. At 10 months after surgery, the transplants were examined histologically. Both grafting and cell-injection methods resulted in porcine spermatogenesis on the backs of recipient mice; the percentage of spermatids present in the transplants was 67% and 22%, respectively. Using the grafting method, all three strains of mice supported the same extent of spermatogenesis. As for the cell- injection method, although SCID mice were the best host for supporting reconstitution and spermatogenesis, any difference from the other strains was not signifcant. As NOG mice did not show any better results, the severity of immunodeficiency seemed to be irrelevant for supporting xeno-ectopic spermatogenesis. Our results confirmed that tubular reconstitution is applicable to porcine testicular cells. This method as well as the grafting method would be useful for studying spermatogenesis in different kinds of animals.     

The value of quantitative DNA flow cytometry of testicular fine-needle aspirates in assessment of spermatogenesis: a study of 137 previously maldescended human testes

In order to assess the suitability of DNA flow cytometry of fine-needle aspirates for quantiftring spermatogenesis, the results from DNA flow cytometry were compared to histological evaluation of testicular biopsies taken concomitantly from 171 previously maldescended testes. In 137 of 171 cases, sufficient material for flow cytometric as well as histological evaluation was obtained.
Histological analysis of surgical biopsy specimens revealed spermatogenesis including the spermatid stage in 117 of the 137 gonads. In six of the 117 gonads no haploid cells were found using flow cytometry. On the other hand, surgical biopsies failed to reveal spermatogenesis in five cases in which the corresponding aspirates contained haploid cells. Both methods therefore seem equally sensitive in detection of spermatogenesis.
Other types of histological patterns also corresponded to distinct DNA histograms.
Thus, in 11 of 12 cases with Sertoli-cell-only pattern in all tubules, at least 95% of the cells had a diploid DNA content. Furthermore, predominance of tubules with maturation arrest at the primary spermatocyte level corresponded to an increased proportion of tetraploid cells.
When compared to surgical biopsy, DNA flow cytometry of testiclar fine-needle aspirates is a more objective, easy and rapid method, which is more convenient for the patient. This study has indicatedthat DNA flow cytometry is a suitable method of quantitative assessment of spermatogenesis. One of the first target groups might be men with azoospermia. In such men, DNA flow cytometric analysis of fine-needle aspirates and surgical biopsy are apparently of equal sensitivity in detecting gonads with spermatogenesis. We conclude that DNA flow cytometry may become an alternative method for the quantification of spermatogenesis.     

雄性生殖细胞体外分化研究现状

生殖细胞的体外研究已建立了多种组织和器官培养系统、精曲小管培养系统、Sertoli细胞和生殖细胞共同培养系统等。随着对血 睾屏障和睾丸细胞极性在体外培养中重要性的逐步重视 ,已初步建立了模拟睾丸分隔结构的双室培养系统和藻酸钙三维培养系统。现有培养系统已经成为深入了解和认识精子发生过程的一种强有力工具。目前在体外已经获得某些动物精子发生的整个减数分裂过程 ,但对雄性生殖细胞体外减数分裂的详细调控机制还知之甚少。本文主要介绍了在雄性生殖细胞体外分化尤其是减数分裂研究方面的发展现状     

Spermatogonial transplantation technique in spermatogenesis research

The spermatogonial stem cell is the foundation of spermatogenesis and it continues to divide throughout the lifetime of a male. It divides to renew itself as well as to produce daughter cells that finally differentiate to spermatozoa. Transplantation of spermatogonial stem cells from a fertile mouse to the testis of a sterile mouse results in the development of donor cell derived spermatogenesis. Furthermore, spermatogenesis of the rat and hamster occurs in immunodeficient mouse testes following spermatogonial transplantation. Cryopreservation of spermatogonial stem cells has been shown to be applicable in many species for later transplantation. In addition, certain forms of infertile donor germ cell can be transplanted to produce functional sperm in a recipient testis. These new techniques will be useful for basic research of spermatogenesis and for application to reproductive technology in the future.     

Androgens and male fertility

Androgens play a crucial role in the development of male reproductive organs such as the epididymis, vas deferens, seminal vesicle, prostate and the penis. Furthermore, androgens are needed for puberty, male fertility and male sexual function. High levels of intratesticular testosterone, secreted by the leydig cells, are necessary for spermatogenesis. Intratesticular testosterone is mainly bound to androgen binding protein and secreted into the seminiferous tubules. Inside the sertoli cells, testosterone is selectively bound to the androgen receptor and activation of the receptor will result in initiation and maintenance of the spermatogenic process and inhibition of germ cell apoptosis. The androgen receptor is found in all male reproductive organs and can be stimulated by either testosterone or its more potential metabolite dihydrotestosterone. Severe defects of the androgen receptor may result in abnormal male sexual development. More subtle modulations can be a potential cause of male infertility. Treatment of an infertile man with testosterone does improve spermatogenesis, since exogenous administrated testosterone and its metabolite estrogen will suppress both GnRH production by the hypothalamus and Luteinising hormone production by the pituitary gland and subsequently suppress testicular testosterone production. Also, high levels of testosterone are needed inside the testis and this can never be accomplished by oral or parenteral administration of androgens. Suppression of testosterone production by the leydig cells will result in a deficient spermatogenesis, as can be seen in men taking anabolic-androgenic steroids. Suppression of spermatogenesis by testosterone administration is also the basis for the development of a male contraceptive. During cytotoxic treatment or irradiation suppression of intratesticular testosterone production cells may prevent irreversible damage to the spermotogonial stem cells.     

The effect of selective destruction and regeneration of rat Leydig cells on the intratesticular distribution of testosterone and morphology of the seminiferous epithelium

This study was designed to explore the relationship between the intratesticular distribution of testosterone and spermatogenesis by completely destroying the Leydig cells of mature male rats with injection of a single i.p. dose of ethane dimethanesulphonate. After such treatment, testosterone levels in serum, testicular interstitial fluid, seminiferous tubules, and whole testis declined significantly 6 to 24 hours after injection and fell below assay detection limits between 3 and 7 days. At 3 and 7 days, serum LH and FSH levels rose significantly and remained elevated up to 4 and 6 weeks, respectively, in comparison with vehicle-treated controls. Leydig cells disappeared from the interstitium by day 3, but between 2 and 4 weeks postinjection a new generation of fetal-like Leydig cells repopulated the testicular interstitium and, during weeks 6 to 10, were transformed into, or replaced by, Leydig cells with an adult type of morphology. Histologic examination of the seminiferous tubules showed progressive disruption of spermatogenesis between 3 and 14 days post-ethane dimethanesulphonate. The first histologic sign of spermatogenic damage was noted at day 3, with the occurrence of stage-specific degenerating pachytene primary spermatocytes at stages VII to VIII of the spermatogenic cycle. On day 7, these cells and degenerating round, or step 19, spermatids often were observed during stages VII to XI, although qualitatively normal spermatogenesis also was seen in these and all other stages of the cycle. Maximum impairment of spermatogenesis occurred 2 weeks post-ethane dimethane sulphonate, at which time the tubules commonly lacked one or more germ cell generations or, alternatively, showed accumulation of lipid inclusions, extracellular spaces, and variable numbers of degenerating germ cells. Following repopulation of the testis by Leydig cells during weeks 3 and 4, spermatogenesis recovered. By 10 weeks after treatment, qualitatively normal spermatogenesis was seen in the great majority of seminiferous tubules, although a few tubules still remained in which the germ cell complement was severely reduced, and contained only Sertoli cells and spermatogonia.(ABSTRACT TRUNCATED AT 400 WORDS)     

Sex steroids and spermatogenesis in the African catfish (Clarias gariepinus)

Little is known about the physiological regulations of spermatogenesis of the African catfish (Clarias gariepinus), a species used as an experimental model for two decades. After a brief introduction to the cystic type of spermatogenesis in fish, the role of androgens and estrogens will be discussed, leading to a conclusion that androgens are required for spermatogenesis while their mode of action is poorly understood. In the cystic mode of spermatogenesis in fish, the Sertoli cells are formed cystic, in the somniferous lobules enclosing a single germ cell clone, providing suitable experimental models to address questions of relevance for vertebrate spermatogenesis in general.