DAZL基因与男性不育关系的研究进展

DAZL基因为DAZ基因家族成员之一,在人类精子发生的过程中,DAZL基因发挥着至关重要的调控作用。基因DAZL通过其表观遗传学修饰作用,主要是DAZ的甲基化,调控基因启动子来实现DAZL基因在生殖细胞中的表达。DAZL基因多态性位点分析(SNP)与男性不育依旧是一个值得探讨的研究方向,目前认为与地域和种族有关。本文通过总结近来的相关研究资料,阐述精子发生过程中的DAZL基因甲基化状态的改变以及DAZL的SNPs与男性不育之间的联系,为男性不育的治疗提供新的理论基础和临床思路。     

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。     

精子的表观遗传学研究进展

表观遗传学是研究DNA序列未发生变化但表型却发生可遗传改变的一门学科,其研究内容包括DNA甲基化、组蛋白修饰、非编码RNA调控等几个方面,任何一方面异常都可能影响染色质的结构和基因表达。在精子发生及受精过程中表观遗传信息都发生了较大变化,因此了解精子的表观遗传学变化对研究后代遗传信息的改变至关重要。本文对精子的表观遗传学信息进行综述,并对辅助生殖技术所带来的遗传风险作简要探讨。     

支持细胞功能状态调控精子发生的研究进展

精子发生是复杂且受紧密调控的过程,其中支持细胞在此过程中发挥着核心作用。支持细胞从不断增殖到形态数量基本不变,从为生殖细胞的发育增殖提供营养到维持生精小管内部微环境的平衡,都与睾丸正常发育以及性成熟后雄性生育力密不可分。本文主要讨论了支持细胞在正常和异常精子发生中的作用与调节,总结了支持细胞数量、结构、表达蛋白及分泌物质变化与精子发生之间的关系,同时也为研究男性不育基因治疗与男性避孕提供参考。     

精子发生的调节机制及其进展

精子发生是一个复杂的过程,受多种因素的精细调节以确保把正确的基因和表观遗传信息传给子代,包括激素(如FSH、LH、T和E2等)、局部调节因子(如FGF9、SHP-2以及VEGF等)以及miRNAs的调节。本文将从精子发生的激素调节、睾丸内的调节因子、miRNAs与精子发生关系等方面的研究进展进行综述。     

精子的表观遗传学研究进展

表观遗传学是研究DNA序列未发生变化但表型却发生可遗传改变的一门学科，其研究内容包括DNA甲基化、组蛋白修饰、非编码RNA调控等几个方面，任何一方面异常都可能影响染色质的结构和基因表达。在精子发生及受精过程中表观遗传信息都发生了较大变化，因此了解精子的表观遗传学变化对研究后代遗传信息的改变至关重要。本文对精子的表观遗传学信息进行综述，并对辅助生殖技术所带来的遗传风险作简要探讨。     

生殖激素受体与精子发生关系的研究进展

精子发生是一个非常复杂的过程,尤其受生殖激素调控。生殖激素与其受体结合在精子的发生、分化、成熟中起着至关重要的作用。因此了解精子发生过程中生殖激素受体的变化对精子发生障碍研究有着重要的价值。本文对生殖激素受体的基因突变及多态性与精子发生的关系进行综述,以期为男性不育的诊治提供帮助。     

精子发生过程中组蛋白翻译后修饰及其作用

<正>精子发生(Spermatogenesis)包括有丝分裂、减数分裂和精子形成3个阶段。精子发生过程中,会不断发生一系列时空特异性的表观遗传调控,其中组蛋白翻译后修饰(Post-translational modifications,PTMs)已成为生殖专家的研究热点。组蛋白包括H1、H2A、H2B、H3、H4 5种,通常可以发生甲基化、磷酸化、乙酰化、泛素化等一种或多种PTMs。组蛋白PTMs是独立存在的,同时不同组蛋白PTMs之间又可以形成不同的组合[1],由于DNA与组蛋白的紧密结合,故组蛋白PTMs在基因转录调控过程中发挥着重要作用,不同位点的组蛋白PTMs对基因表达的作用不同,同一位点上组蛋白PTMs数目不同对基因表达的影响也不同[2],因此组蛋白PTMs扩大了DNA密     

精子发生的基因调控

在精子发生的整个过程中,基因的表达和调控都起着至关重要的作用。在有丝分裂阶段的精原细胞中有405个基因表达;精母细胞中无DNA复制,DNA修复至关重要,许多基因参与这个过程中的基因重组与DNA修复,有442个基因高表达于精母细胞;在减数分裂后的精子细胞中有175个基因表达[1]。本文对调控精子发生的常见基因作一综述。一、正常精子发生过程由精原干细胞经过一系列发育阶段发展成为精子的过程称为精子发生。哺乳动物的精子发生可分为3个阶段:①精原细胞经过数次有丝分裂,增殖分化为初级精母细胞;②初级精母细胞经过减数分裂(中间经过短暂的…     

睾丸细胞间隙连接通道的研究进展

睾丸里的生殖细胞从增殖、减数分裂到分化成熟是一个受到严格调控的过程,这个过程需要睾丸细胞间密切的联系.间隙连接是位于细胞膜上连接相邻细胞间的通路,在精子发生的启动和维持上有重要作用.本文着重介绍哺乳动物睾丸中细胞的间隙连接通道,连接蛋白的分布、其对精子发生的重要作用以及连接蛋白的调控因子等.并对病理状态下睾丸组织细胞间的间隙连接和连接蛋白的变化进行概要介绍.     

Epigenetics and oxidative stress: A twin‐edged sword in spermatogenesis

Spermatogenesis is a series of complex events involving a delicate balance between cell proliferation and cell differentiation. Aggregation of chromatins and epigenetic modifications play a vital role in spermatogenesis via regulation of molecular pathways to maintain testicular homeostasis. These epigenetic mechanisms consist of histone modification, chromatin remodelling, DNA methylation and miRNA, etc., which reportedly are critical players in spermatogenesis. One such mechanism involves regulation of oxidative stress in the male reproductive system. The fact that testicular cells contain plenty of unsaturated fatty acids and undergo division at a high rate makes spermatogenic cells highly susceptible to oxidative insult leading to deleterious effect on spermatozoa, which may culminate in infertility in men. Although the correlation between ROS‐mediated oxidative stress and epigenetic alterations has been indicated, research in this regard is still in infancy. Further, the fact that environmental and life style factors are critical determinants of spermatogenic potential indicates the importance of epigenetic regulation of key molecular events in spermatogenesis. Therefore, the current review aims to discuss the ROS‐induced epigenetic deregulation of the molecular mechanism(s) involved in spermatogenesis.     

The effects of diabetes on male fertility and epigenetic regulation during spermatogenesis

The effects of diabetes mellitus include long-term damages, dysfunctions, and failures of various organs. An important complication of diabetes is the disturbance in the male reproductive system. Glucose metabolism is an important event in spermatogenesis. Moreover, glucose metabolism is also important for maintaining basic cell activity, as well as specific functions, such as motility and fertilization ability in mature sperm. Diabetic disease and experimentally induced diabetes both demonstrated that either type 1 diabetes or type 2 diabetes could have detrimental effects on male fertility, especially on sperm quality, such as sperm motility, sperm DNA integrity, and ingredients of seminal plasma. Epigenetic modifications are essential during spermatogenesis. The epigenetic regulation represents chromatin modifications including DNA methylation, histone modifications, remodeling of nucleosomes and the higher-order chromatin reorganization and noncoding RNAs. If spermatogenesis is affected during the critical developmental window, embryonic gonadal development, and germline differentiation, environmentally-induced epigenetic modifications may become permanent in the germ line epigenome and have a potential impact on subsequent generations through epigenetic transgenerational inheritance. Diabetes may influence the epigenetic modification during sperm spermatogenesis and that these epigenetic dysregulation may be inherited through the male germ line and passed onto more than one generation, which in turn may increase the risk of diabetes in offspring.     

How defective spermatogenesis affects sperm DNA integrity

Spermatogenesis is the essential process to maintain and promote male fertility. It is extraordinarily complex with many regulatory elements and numerous steps. The process involves several cell types, regulatory molecules, repair mechanisms and epigenetic regulators. Evidence has shown that fertility can be negatively impacted by reduced sperm DNA integrity. Sources of sperm DNA damage include replication errors and causes of DNA fragmentation which include abortive apoptosis, defective maturation and oxidative stress. This review outlines the process of spermatogenesis, spermatogonial regulation and sperm differentiation; additionally, DNA damage and currently studied DNA repair mechanisms in spermatozoon are also covered.     

The paternal epigenome and embryogenesis: poising mechanisms for development

The scope of paternal contributions during early embryonic development has long been considered limited. Dramatic changes in chromatin structure throughout spermatogenesis have been thought to leave the sperm void of complex layers of epigenetic regulation over the DNA blueprint, thus leaving the balance of that regulation to the oocyte. However, recent work in the fields of epigenetics and male factor infertility has placed this long-held, and now controversial dogma, in a new light. Elegant studies investigating chromatin and epigenetic modifications in the developing sperm cell have provided new insights that may establish a more critical role for the paternal epigenome in the developing embryo. DNA methylation, histone tail modifications, targeted histone retention and protamine incorporation into the chromatin have great influence in the developing sperm cell. Perturbations in the establishment and/or maintenance of any of these epigenetic marks have been demonstrated to affect fertility status, ranging in severity from mild to catastrophic. Sperm require this myriad of chromatin structural changes not only to serve a protective role to DNA throughout spermatogenesis and future delivery to the egg, but also, it appears, to contribute to the developmental program of the future embryo. This review will focus on our current understanding of the epigenetics of sperm. We will discuss sperm-specific chromatin modifications that result in genes essential to development being poised for activation early in embryonic development, the disruption of which may result in reduced fecundity.     

精子的表观遗传学与胚胎发育关系的研究进展

表观遗传学是研究DNA序列未发生变化但表型发生可遗传改变的一门学科。精子在其发生和受精过程中表观遗传信息都发生了较大变化,而这些改变将直接影响受精后的胚胎发育,因此研究精子的表观遗传学与胚胎发育有重要的意义。本文从精子的DNA甲基化、组蛋白修饰、非编码RNA调控和基因印记4个方面对精子的表观遗传学改变及其对胚胎发育的影响作简要探讨。     

睾丸CR16与精子发生

精子发生是依靠各种激素(FSH、LH、T、17β雌二醇)、细胞因子和基因调节的复杂调控过程。基因调控在精子发生中的研究已逐渐成为热点,已发现的与精子发生相关的基因,如AYZ、DAZ、YRRM、NOSTRIN等。但目前关于CR16在男性生殖方面的报道尚不多见,其在精子发生中的作用机制并不十分清楚,本文主要从支持细胞形成血睾屏障角度,对CR16在男性生殖系统精子发生中的研究做一综述。     

血红素氧合酶-一氧化碳体系在生殖调节中的作用

血红素氧合酶-一氧化碳体系是体内重要的生物活性物质,其广泛表达人类生殖系统,参与调节睾丸精子生成及精液参数、卵泡发育、胚泡发育及母胎血供、母胎界面免疫调节等生殖过程.本文对血红素氧合酶-一氧化碳体系在生殖调节中的作用进行综述.