Incomplete protection of genetic integrity of mature spermatozoa against oxidative stress

Jin²,

et al. 2012

PLoS ONE

The testis is a highly specialized tissue that plays dual roles in ensuring fertility by producing spermatozoa and hormones. Spermatogenesis is a complex process, resulting in the production of mature sperm from primordial germ cells. Significant structural and biochemical changes take place in the seminiferous epithelium of the adult testis during spermatogenesis. The gene expression pattern of testis in Chinese mitten crab (Eriocheir sinensis) has not been extensively studied, and limited genetic research has been performed on this species. The advent of high-throughput sequencing technologies enables the generation of genomic resources within a short period of time and at minimal cost. In the present study, we performed de novo transcriptome sequencing to produce a comprehensive transcript dataset for testis of E. sinensis. In two runs, we produced 25,698,778 sequencing reads corresponding with 2.31 Gb total nucleotides. These reads were assembled into 342,753 contigs or 141,861 scaffold sequences, which identified 96,311 unigenes. Based on similarity searches with known proteins, 39,995 unigenes were annotated based on having a Blast hit in the non-redundant database or ESTscan results with a cut-off E-value above 10−5. This is the first report of a mitten crab transcriptome using high-throughput sequencing technology, and all these testes transcripts can help us understand the molecular mechanisms involved in spermatogenesis and testis maturation.

Section: Discussionmentioning

confidence: 99%

Transcriptome Profiling of Testis during Sexual Maturation Stages in Eriocheir sinensis Using Illumina Sequencing

Jin²,

et al. 2012

PLoS ONE

“…Thus the primary trigger for activation of the intrinsic apoptotic cascade could, curious as it may sound, be the induction of a mild oxidative stress. The latter could arise in any number of ways including poor antioxidant protection within the male or female reproductive tract as a result of dietary deficiencies (Palmer et al, 2012), age (Weir and Robaire, 2007), varicocele (Mostafa et al, 2001), cryostorage , exposure to lifestyle factors (Fraga et al, 1996;Linschooten et al, 2011), medicinal compounds (Ghosh et al, 2002), bacteria (Villegas et al, 2005;Fraczek et al, 2007), prolonged incubation in vitro or in vivo (Balasuriya et al, 2013) and a range of environmental factors including non-ionizing radiation (Agarwal et al, 2009;). All such factors converge in the generation of oxidative stress within the spermatozoa.…”

Section: Activation Of Mitochondrial Reactive Oxygen Species Generatimentioning

confidence: 99%

Causes and consequences of apoptosis in spermatozoa; contributions to infertility and impacts on development

Aitken¹,

Baker²

2013

Int. J. Dev. Biol.

169

108

During early development, apoptosis plays a major role in the ontogeny of the germ line as a means of regulating the germ cell:Sertoli cell ratio. In the adult, apoptosis fulfils another function in removing damaged germ cells from the seminiferous epithelium in response to a wide range of physiological and environmental triggers. These include various forms of electromagnetic radiation, chemotherapeutic agents and commonly encountered toxicants such as phthalate esters, bisphenol A and cadmium. This form of apoptosis can lead to spermatogenic arrest and is predominantly mediated by the Fas/FasL system. In addition, senescent mature spermatozoa can undergo a truncated form of apoptosis in order to ensure their efficient phagocytosis within the male and female reproductive tracts. This apoptotic cascade appears to be triggered by oxidative stress and lipid peroxidation, which leads to activation of mitochondrial reactive oxygen species (ROS) generation in a self-perpetuating redox cycle. The electrophilic aldehydes generated as a result of lipid peroxidation also lead to a rapid loss of sperm motility followed some hours later by caspase activation and phosphatidylserine exposure on the sperm surface. The nuclear DNA suffers oxidative damage during this process but there is no immediate DNA cleavage by endonucleases as there is in somatic cells. The reasons for this deviation from the normal pattern of apoptosis involve the unusual physical architecture of spermatozoa and the limited capacity these cells possess for base-excision repair. These findings have practical implications for the approaches that might be used to detect and prevent DNA damage in spermatozoa. KEY WORDS: spermatozoa, apoptosis, reactive oxygen species, mitochondria DNA damage Apoptosis and male germ cell developmentApoptosis is a major feature of male germ cell development that orchestrates the production and function of these cells from the early stages of gonadal differentiation to the moment of fertilization. Towards the end of embryogenesis a major wave of germ cell apoptosis occurs in prospermatogonia/gonocytes when the testes are differentiating and adjustments have to be introduced to achieve the optimal germ cell:Sertoli cell ratio. During this developmental process, excess premeiotic spermatogonia are removed by apoptosis during the first round of spermatogenesis in the testis. Impairment of apoptosis through the functional deletion of key mediators of this process generates a male infertility phenotype due to an imbalance in germ-and Sertoli-cell numbers (Rodriguez et al., 1997). This regulatory role for apoptosis in the male germ cell development is very similar to the situation in the differentiating female gonad where there is also a wave of apoptosis in the ovary Int. J. Dev. Biol. 57: 265-272 (2013) as germ cells are eliminated that have not found somatic cells with which to form primordial follicles .In adulthood, apoptosis again plays a significant role in regulating germ cell development. For example, apoptosis ...

“…ROS-mediated damage to sperm is a significant contributing factor in 30-80% of infertile men [6–9, 20]. The antioxidant system present in semen [21, 22] is then not sufficient to protect sperm from ROS-dependent damage such as peroxidation of membrane lipids [23], DNA fragmentation and oxidation of bases [24, 25], low mitochondrial membrane potential [26, 27] and inactivation of enzymes associated with motility [28, 29]. …”

Section: Introductionmentioning

confidence: 99%

“…This particularity is due to high content of polyunsaturated fatty acids in the plasma membrane, target for extensive oxidation, little cytoplasm and thus low capacity for antioxidant protection by cytoplasmic enzymes (e.g. Cu-Zn SOD) and limited DNA repair mechanisms [22, 109–111]. These deficiencies can be worsen if the PRDX system is altered by oxidative stress; because PRDXs are easily oxidized even at low ROS concentration, the presence of an oxidative stress in human spermatozoa will alter the capacity of these enzymes to scavenge excessive amounts of ROS.…”

Section: Introductionmentioning

confidence: 99%

Peroxiredoxins: hidden players in the antioxidant defence of human spermatozoa

O’Flaherty

2014

Basic Clin. Androl.

Spermatozoon is a cell with a precious message to deliver: the paternal DNA. Its motility machinery must be working perfectly and it should be able to acquire fertilizing ability in order to accomplish this mission. Infertility touches 1 in 6 couples worldwide and in half of the cases the causes can be traced to men. A variety of conditions such as infections of the male genital tract, varicocele, drugs, environmental factors, diseases, smoking, etc., are associated with male infertility and a common feature among them is the oxidative stress in semen that occurs when reactive oxygen species (ROS) are produced at high levels and/or when the antioxidant systems are decreased in the seminal plasma and/or spermatozoa. ROS-dependent damage targets proteins, lipids, and DNA, thus compromising sperm function and survival. Elevated ROS in spermatozoa are associated with DNA damage and decreased motility. Paradoxically, ROS, at very low levels, regulate sperm activation for fertilization. Therefore, the regulation of redox signaling in the male reproductive tract is essential for fertility. Peroxiredoxins (PRDXs) play a central role in redox signaling being both antioxidant enzymes and modulators of ROS action and are essential for pathological and physiological events. Recent studies from our lab emphasize the importance of PRDXs in the protection of spermatozoa as infertile men have significant low levels of PRDXs in semen and with little enzymatic activity available for ROS scavenging. The relationships between sperm DNA damage, motility and lipid peroxidation and high levels of thiol-oxidized PRDXs suggest the enhanced susceptibility of spermatozoa to oxidative stress and further support the importance of PRDXs in human sperm physiology. This review aims to characterize PRDXs, hidden players of the sperm antioxidant system and highlight the central role of PRDXs isoforms in the protection against oxidative stress to assure a proper function and DNA integrity of human spermatozoa.