Whither must spermatozoa wander？ The future of laboratory seminology

This commentary celebrates the publication of the 5th for the Examination and Processing of Human Semen edition of the World Health Organization Laboratory Manual This is the most complete text to date on the creation of a conventional semen profile and includes invaluable reference limits for specific aspects of semen quality based on the analysis of over 1 900 recent fathers. The new edition of the manual also includes detailed protocols for monitoring different aspects of sperm function and new chapters on the preparation of spermatozoa for assisted conception and cryopreservation. Given that this publication is the definitive statement on how to perform a descriptive semen analysis, we might speculate on the future of this field and the sorts of tests that might feature in future editions of the manual. Cell biologists are currently being empowered by the ＇omics revolution, which is placing at their disposal technologies of unprecedented power to examine the biochemical composition of cells such as spermatozoa. Indeed, spermatozoa are perfect vehicles for this kind of analysis because they can be obtained as extremely pure suspensions, exist naturally in isolation and can be induced to express their capacity for fertilization and the initiation of embryonic development in vitro. The application of ＇omics technologies to these cells, in concert with detailed assessments of their functional competence, should provide insights into the biochemical basis of defective semen quality. This information will then help us understand the causes of male infertility and to develop rational methods for its treatment and possible prevention.

Apoptosis and DNA damage in human spermatozoa

DNA damage is frequently encountered in spermatozoa of subfertile males and is correlated with a range of adverse clinical outcomes including impaired fertilization, disrupted preimplantation embryonic development, increased rates of miscarriage and an enhanced risk of disease in the progeny. The etiology of DNA fragmentation in human spermatozoa is closely correlated with the appearance of oxidative base adducts and evidence of impaired spermiogenesis. We hypothesize that oxidative stress impedes spermiogenesis, resulting in the generation of spermatozoa with poorly remodelled chromatin. These defective cells have a tendency to default to an apeptotic pathway associated with motility loss, caspase activation, phosphatidylserine exteriorization and the activation of free radical generation by the mitochondria. The latter induces lipid peroxidation and oxidative DNA damage, which then leads to DNA fragmentation and cell death. The physical architecture of spermatozoa prevents any nucleases activated as a result of this apoptotic process from gaining access to the nuclear DNA and inducing its fragmentation. It is for this reason that a majority of the DNA damage encountered in human spermatozoa seems to be oxidative. Given the important role that oxidative stress seems to have in the etiology of DNA damage, there should be an important role for antioxidants in the treatment of this condition. If oxidative DNA damage in spermatozoa is providing a sensitive readout of systemic oxidative stress, the implications of these findings could stretch beyond our immediate goal of trying to minimize DNA damage in spermatozoa as a prelude to assisted conception therapy.

Proteomic changes in mammalian spermatozoa during epididymal maturation

Epididymal maturation is associated with the activation of a cAMP-induced tyrosine phosphorylation cascade, which is ultimately associated with the expression of capacitation-dependent sperm functions, such as hyperactivated movement and acrosomal exocytosis. As spermatozoa progress through the epididymis they first acquire the capacity to phosphorylate tyrosine on targets on the principal piece, followed by the midpiece. By the time these cells have reached the cauda epididymidis they can phosphorylate the entire tail from neck to endpiece. This particular pattern of phosphorylation is associated with the ontogeny of fully functional spermatozoa that are capable of fertilizing the oocyte. Proteomic analyses indicate that this change is associated with the phosphorylation of several mitochondrial proteins, creation of a mitochondrial membrane potential and activation of mitochondrial free radical generation. At least in rodent species, activation of sperm mitochondria appears to be a particularly important part of epididymal maturation. （Asian J Androl 2007 July; 9： 554-564）

Cellular mechanisms regulating sperm-zona pellucida interaction

For mammalian spermatozoa to exhibit the ability to bind the zona pellucida （ZP） they must undergo three distinct phases of maturation, namely, spermatogenesis （testis）, epididymal maturation （epididymis） and capacitation （female reproductive tract）. An impressive array of spermatozoa surface remodeling events accompany these phases of maturation and appear critical for recognition and adhesion of the outer vestments of the oocyte, a structure known as the ZP. It is becoming increasingly apparent that species-specific zona adhesion is not mediated by a single receptor. Instead, compelling evidence now points toward models implicating a multiplicity of receptor-ligand interactions. This notion is in keeping with emerging research that has shown that there is a dynamic aggregation of proteins believed to be important in sperm-ZP recognition to the regions of sperm that mediate this binding event. Such remodeling may in turn facilitate the assembly of a multimeric zona recognition complex （MZRC）. Though formation of MZRCs raises questions regarding the nature of the block to polyspermy, formation and assembly of such a structure would no doubt explain the strenuous maturation process that sperm endure on their sojourn to functional maturity.

Spermatids do it differently! Paip2a--the essential regulator of spermiogenesis？

The mechanisms underpinning the latter stages of spermiogenesis are poorly understood and male germ cells have been presumed to extensively employ post-tran- scriptional regulatory machinery,

精子相关研究何去何从——实验精液学的未来

首先祝贺《世界卫生组织人类精液分析实验室技术手册》(简称手册)第5版的出版,这是迄今为止最完善的关于精液常规检测的手册。基于对1900名"新爸爸"的精液分析结果,WHO手册发布了有重要参考价值的精子质量检测参考值范围,还详细介绍了精子功能检测的方案,并增加了关于辅助生殖和冷冻保存时精液处理的新章节。该手册是关于精液常规检测的权威描述,有可能对该领域的未来以及手册未来发展版本的实验技术进行预测。如今,已可应用空前强大的分析技术检测包括精子在内的各类细胞的生化组成。事实上,精子是进行这种分析的完美载体,因为可获得非常纯净的精子悬液,精子天然游离存在,并可以在体外受精进而启动胚胎发育。在这些检测中各种组学技术的应用以及与此匹配的功能评估应该为精液质量缺陷的研究提供生化基础。这些信息将有助于了解男性不育症的原因,并制定合理的治疗方法和可能的预防措施。