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Cover story


Vol.19  No.4
SPION targeting of ADSCs in diabetic ED Stem cell therapy is a promising new frontier for the treatment of diabetic erectile dysfunction. However, inadequate cell homing to damaged sites has limited their efficacy. In the current study, we labelled adipose tissue-derived stem cells (ADSCs) with a conventional magnetic resonance imaging contrast agent, superparamagnetic iron oxide nanoparticles (SPIONs), and demonstrated that application of an external magnetic field could improve the in vivo homing efficiency of ADSCs to the corpus cavernosum region and contribute to the improvement in erectile function of diabetic rats. Besides, our further research suggested that the paracrine effect of ADSCs appeared to play the major role in functional and structural recovery. In conclusion, our study provides evidence that magnetic field-guided ADSC therapy is an efficient approach for diabetic ED therapy. Please refer to pages 425-432 by Zhu et al. for details. (Artwork is displayed by Xiang Chen)

Vol.19  No.3
PSMA-SPECT/CT and PCa metastatic lesions Using conventional imaging modalities, it is difficult to detect recurrent lesions in prostate cancer patients who have undergone biochemical relapse. We retrospectively reviewed fifty patients with histopathologically confirmed prostate cancer who underwent 99mTc labeled PSMA-SPECT/CT, MRI, and bone scan. PSMA-SPECT/CT indicated metastatic lesions in 39 patients and had a higher detection rate than bone scan or MRI. The diagnostic efficiency of PSMA-SPECT/CT imaging for bone and lymph node metastases was better than bone scan or MRI. PSMA SPECT/CT provided a higher detection rate at different PSA levels. No correlation was found between Gleason score, PSA level, and the tracer tumor/background ratio of metastatic lesions. With the aid of PSMA SPECT/CT imaging, the therapeutic strategy was changed for 31 patients, and this may have enhanced their clinical outcome. In conclusion, PSMA SPECT/CT imaging could achieve a higher detection rate than conventional imaging modalities in prostate cancer patients who had undergone biochemical relapse. Please refer to pages 267–271 by Su et al. for details. (Artwork is displayed by Xiang Chen)

Vol.19  No.2
Inconsistency of PSA and BSI during CRPC Upper figure: The level of bone metastasis, Bone Scan Index (BSI) on bone scintigraphy, was decreased by androgen deprivation therapy (ADT), and subsequently was increased to the level of pre-ADT on CRPC. Lower figure: Prostate Specific Antigen (PSA) quickly decreases because ADT inactivates PSA promoter, and subsequently decreases gradually due to apoptosis. Then PSA become stable on proliferation quiescence. Finally, PSA increases on relapse. However, PSA level is still low compared with high BSI (Upper figure). One reason of this inconsistency is supposed with tumor volume effect rather than the effect of hypersensitive AR. Please refer to pages *-* of the article by A. Mizokami for details. (Artwork is displayed by Xiang Chen)

Vol.19  No.1
The effects of in vivo oxidative stress on epididymal maturation promote a shut-down of the PRDX system that will be translated in a deterioration of sperm quality characterized by increased sperm DNA oxidation and impaired sperm motility. The in vivo-induced oxidative stress triggers a differential expression of peroxiredoxins (PRDXs) in different segments of the epididymis and the transfer of PRDXs to the maturating spermatozoa to protect them against the high levels of ROS produced. However, when the PRDXs system is overcome by the established oxidative stress, PRDXs become highly oxidized (displaying oxidation of the thiol groups in their active site) and unable to protect spermatozoa against oxidative damage. This outcome is seen in infertile men with very low amount of PRDXs or when these enzymes are inactivated. Our findings highlight the major role of PRDXs in the antioxidant protection of spermatozoa. For more information, please refer to the article on pages 73-79. (The image is from Dr. O’Flaherty’s article, and artwork is displayed by Xiang Chen).

Vol.18  No.6
Sperm Morphometrics Today and Tomorrow
Sperm morphology has long been considered an important factor in male fertility, but assessing it has been bedevilled by the subjective nature of deciding if a particular sperm cell is normal or abnormal, why it falls into either category and how that decision is made. The development of machines that assess sperm morphology quantitatively (computer-aided sperm analysis for morphology) offered a solution by providing dimensions of spermatozoa, but this approach is limited when statistical analysis is applied separately to each parameter. The combination of CASA-Morph and multi-parametric statistical analyses, such as principal component analysis, offers a way forward, since subpopulations of spermatozoa of different morphometry are generated, the presence or size of which may well be diagnostic for infertility and prognostic for fertility. This Special Issue explains these procedures and shows how they can be applied to the analysis of spermatozoa from man and a range of commercially important species whose fertility is well documented. (The image is from Jesús L Yániz et al., and artwork is displayed by Xiang Chen)

Vol.18  No.5
Intrinsically Disordered Proteins and Prostate Cancer
Conventional wisdom dictates that cancer is a genetic disease emphasizing the deterministic nature of its underlying plasticity. Thus, phenotypic plasticity, a hallmark of the disease is thought to be driven by a series of genomic mutations and therefore, irreversible. Contrary to this wisdom, new thinking presented here explores the possibility that stochasticity which is inherent to nonlinear systems may also play an important role. The theory underscores conformational dynamics of intrinsically disordered proteins (IDPs) as the main driver of phenotypic plasticity in cancer cells. By rewiring protein interaction networks characteristic of a given phenotype, it is postulated that IDPs can reversibly facilitate state switching in a manner analogous to a phase transition phenomenon. Thus, targeting key IDPs or intrinsically disordered regions within ordered proteins such as the N-terminal domain of the androgen receptor rather than highly ordered domains such as its ligand-binding domain may provide novel and highly effective therapeutics for prostate cancer. (The photos are provided by Prof. Prakash Kulkarni. The artwork is displayed by Xiang Chen)

Vol.18  No.4
Translation of Genomics and Epigenomics in Prostate Cancer
Translation of Genomics and Epigenomics in Prostate Cancer The Pyramid Model illustrates a paradigm for personalized medicine that promotes a proactive approach for prostate cancer care from screening and diagnosis, to the treatment of early- and late-stage diseases. The personalization of clinical practice is conducted primarily by assessing inherited and acquired changes in both DNA and RNA. In the lowest tier, inherited genetic variants can be used to assess risk for prostate cancer to determine who should undergo PSA screening. In higher tiers, DNA- and RNA- based methods can be used to assess prognosis (i.e. predict lethality) and/or select specific therapies for men who have been diagnosed. For example, DNA copy number alterations can be assessed in early-stage disease to help determine the likelihood of cancer progression, and an androgen receptor variant in tumor DNA can confer resistance to specific antiandrogen drugs. Implementation of the Pyramid Model into clinical care has the potential to improve quality of life, decrease mortality, and decrease costs. (Art by Xiang Chen).

Vol.18  No.3
Basic Concepts &Recent Advancements in Male Fertility
Images highlighting stages of a microsurgical varicocele repair. Following sub-inguinal incision, the spermatic cord is identified and brought into the operative field (Panel 1). Under magnification, cremasteric fibers are separated and placed underneath a knife handle keeping the cord elevated in the incision. Vas deferens and veins are easily identified. Intra-operative auscultation of the testicular artery initially characterizes the location (Panel 2). 2-0 silk ties are threaded underneath each vein superior and inferiorly. The vein is subsequently tented and occluded while the artery is auscultated distally. Patency of the testicular artery is confirmed prior to final venous occlusion. Fine Jacobson mosquitos pass 2-0 silk ties underneath spermatic cord veins (Panel 3). Veins can be transected to gain access to deeper venous structures or tied if large/peripheral (Panel 4). Lymphatic structures are tagged. Some ties are left long allowing for retraction and improved visualization of cord structures (Panel 5). Completed repair finds numerous tied and/or transected vessels (Panel 6). Care was taken to preserve the testicular artery, vas deferens and lymphatic structures. (The photos are provided by Dr. Jason R. Kovac. The artwork is displayed by Xiang Chen)

Vol.18  No.2
Varicocele and Male Infertility
Oxidative stress is the central and common pathogenic mediator of testicular damage in varicocele, and exposure to heat, hypoxia and toxic adrenal and renal metabolites are stimulators of reactive oxygen and nitrogen species generation. ROS encompass a broad category of highly reactive substances formed as byproducts of oxidative and reductive metabolic reactions. Reactive nitrogen species constitute a subset of ROS that contains nitrogen atoms. Three components can release ROS in men with varicocele under heat and hypoxic stress: the principal cells in the epididymis, the endothelial cells in the dilated pampiniform plexus and the testicular cells (developing germ cells, Leydig cells, macrophages and peritubluar cells). An imbalance between ROS and their neutralizing antioxidants in men with varicocele results in oxidative stress that is mediated through a variety of mechanisms and target lipids, proteins, sugars and nucleic acids. Excessive ROS overwhelm primary sperm defenses against oxidative stress — the tight packing of sperm DNA and seminal antioxidants. The harmful effects of oxidative stress include peroxidation of sperm membranes and changes in membrane fluidity, and nuclear and mitochondrial sperm DNA damage. (Adapted by permission from Macmillan Publishers Ltd: Nature Reviews Urology. Agarwal A, Hamada A, Esteves SC: Insight into oxidative stress in varicocele-associated male infertility: part 1. issue 9, pages 678–690, 2012). The artwork is displayed by Xiang Chen.

Vol.18  No.1
Vasoepididymostomy (VE), as the most challenging procedure in microsurgeries, is often carried out with a double-armed two-suture technique. However, suitable and cost-effective high quality double-armed micro-sutures for male infertility microsurgeries are not easy to obtain. In this study, we evaluated the efficacy and safety of the single-armed two-suture longitudinal intussusception microsurgical VEs on humans by a single surgeon (Dr. Kai Hong), and studied the factors that could possibly affect the patency rates. The single-armed two-suture longitudinal VE technique is feasible for microsurgical practice. The patency and pregnancy rates are comparable to the doubled-armed technique. Anastomosis sites and motile sperm found in epididymal fluid were the most two important factors related to higher patency. For more information, please refer to the article on pages 129-133. (The image is from Dr Hong’s article, and artwork is displayed by Xiang Chen)

Vol.17  No.6
The International Prostate Forum is a collaborative group from the United States, Japan, and Turkey that focuses on clinical and translational science research related to prostate cancer and benign diseases. On the cover of this issue, we blend iconic symbols from these three countries. The bald eagle shown is the national bird of the United States of America. It was chosen because of its long life, great strength, majestic looks, and is symbol of freedom. The Hagia Sophia museum is in Istanbul, Turkey. It was initially a Greek Orthodox cathedral, and later became a mosque. It is a symbol of great architecture, and a unique co-existence of Christian and Muslim history and art. From Japan, the orange floating torii at the Itsukushima Shrine is located on Miyajima island near Hiroshima. A torii makes the entrance to a sacred space.

Vol.17  No.5
Within the intraluminal compartment of the epididymis, maturing spermatozoa interact with heterogeneous populations of extracellular vesicles (EVs) referred to as epididymosomes. In addition to playing a role in the acquisition of new proteins on the sperm surface, these EVs transport small-non-coding RNAs called microRNAs, which may participate in a well-orchestrated intercellular communication system between somatic and germinal cells. According to several knock-out mouse models, these major regulators of post-transcriptional gene expression have been shown to be involved in the control of male fertility. Distinct microRNAs species being produced and secreted by the internal organs of the male reproductive system, and present in seminal plasma at ejaculation, they constitute potential new molecular targets for the non-invasive diagnosis of idiopathic male infertility. Please refer to pages 730–736 of the article by C. Belleannée for details.(The graphic design contribution of France Couture from CHU de Quebec, Canada, is acknowledged, and artwork is displayed by Xiang Chen)

Vol.17  No.4
The 12 th International Symposium on Spermatology
Fluorescent image of an echidna spermatozoa bundle in which the nuclei are labelled with 4’,6-diamidino-2-phenylindole (DAPI). A unique feature of the monotreme epididymis lies in its ability to promote the formation of elaborate v-shaped bundles of up to 100 individual spermatozoa that are held together by an electron dense material that embeds the anterior region of the sperm heads. This image depicts a sperm bundle that has fanned out, a phenomenon that occurs immediately before the bundles disperse to release individual spermatozoa. (The cover image is provided by Dr Brett Nixon, Discipline of Biological Sciences, University of Newcastle, Australia, and artwork is displayed by Xiang Wang)

Vol.17  No.3
Germinal Stem Cell Biology
Spermatogenesis comprises a first phase leading to spermatogonial stem cells from transitional gonocytes, and a second spending from differentiating spermatogonia to sperm. This life-long process involves multiple steps of cell migration, differentiation, mitotic and meiotic divisions. Apoptosis plays a critical role as quality control system by eliminating defective germ cells, and in maintaining an adequate microenvironment by regulating germ to Sertoli cell ratio. While gonocytes undergo retinoic acid-induced differentiation, disrupting this process may lead to testicular cancer. In this issue, Manku and Culty examined the expression of 84 apoptosis-related genes in gonocytes, spermatogonia and seminomas. Functional partner predictions of upregulated genes in differentiating gonocytes using STRING analysis (Search Tool for the Retrieval of Interacting Genes/Proteins) identified a pro-survival cluster radiating from Akt, beside the main pro-apoptotic cluster around Caspase 3, suggesting a balance between pro- and anti-apoptotic genes at this point, preceding the first postnatal wave of apoptosis. For more information, please refer to the article on pages 403–414. (The image is from Manku and Culty’s article, and artwork is displayed by Xiang Chen)

Vol.17  No.2
Controversies in testosterone supplementation therapy(TST)
Testosterone supplementation therapy (TST) has been rapidly expanding throughout the world. The rapid rise in TST may be due in part to the newly recognized beneficial effects seen with testosterone. Patients taking TST have experienced improvements in sexual desire, libido, depression, muscle mass, fat deposition, and overall energy. As our population ages, more and more men are now becoming candidates for testosterone supplementation therapy.

Vol.17  No.1
Cardiovascular disease and male sexual dysfunction Erectile dysfunction (ED) and cardiovascular disease (CVD) are increasingly common in the aging male population. The common link between these conditions is atherosclerosis and its underlying risk factors. This correlation between CVD and ED is now well-established and should be recognized by health care professionals, as well as by couples afflicted with ED. Modification of risk factors such as obesity, hypertension, diabetes, sedentary lifestyle and dyslipidemia may improve or limit further deterioration of ED. As a result, overall and sexual health can be positively impacted and increase the couple’s intimacy. Hypogonadism and its treatments, which are closely related to CVD and ED, are also important diagnostic and treatment considerations in this patient population. (Art by Xiang Chen)

Vol.16  No.6
The average body mass index (BMI) is generally rising for both men and women in the Western world and along with this a concern for the possible harmful effect on the reproductive potential has emerged. It is well known that female weight disturbances affect fertility negatively and as a consequence, many European fertility clinics require female weight loss to a specific BMI threshold before initiating assisted reproductive technology (ART) treatment. From the male perspective, however, it is still unclear to what extent overweight and obesity affect sperm quality and the chances of conceiving-spontaneously as well as after ART. The relatively limited data published are conflicting and, therefore, it is still uncertain whether male weight loss will increase natural or assisted fertility. In this issue, Thomsen et al. investigate whether increased male BMI affects sperm quality and the outcome of assisted reproduction in 612 couples undergoing ART treatment at a Danish Fertility Centre. For more information, please refer to the article on pages 749–754. (Art by Xiang Chen)

Vol.16  No.5
The average body mass index (BMI) is generally rising for both men and women in the Western world and along with this a concern for the possible harmful effect on the reproductive potential has emerged. It is well known that female weight disturbances affect fertility negatively and as a consequence, many European fertility clinics require female weight loss to a specific BMI threshold before initiating assisted reproductive technology (ART) treatment. From the male perspective, however, it is still unclear to what extent overweight and obesity affect sperm quality and the chances of conceiving-spontaneously as well as after ART. The relatively limited data published are conflicting and, therefore, it is still uncertain whether male weight loss will increase natural or assisted fertility. In this issue, Thomsen et al. investigate whether increased male BMI affects sperm quality and the outcome of assisted reproduction in 612 couples undergoing ART treatment at a Danish Fertility Centre. For more information, please refer to the article on pages 749–754. (Art by Xiang Chen)

Vol.16  No.4
Prostate cancer patients die as a result of metastasis to bone and soft tissue. To disseminate through complex microenvironments, cancer cells employ diverse strategies. Amoeboid invasion is a rapid mode of tumor cell motility in which actomyosin contractility and propulsive forces enable cells to traverse spaces between fibrillar matrices. Amoeboid behavior is mediated by RhoA/ROCK activation, integrin localization, cytoskeletal dynamics, receptor stimulation, and loss of Diaphanous-related formin-3 (DIAPH3). Amoeboid cells shed extracellular vesicles (EVs), called ‘large oncosomes,’ which enable cross-talk with the tumor stroma. Morley et al summarize the current understanding of amoeboid invasion. For more information, please refer to the article on pages 530–535. (The image was created by Samantha Morley, and artwork is displayed by Xiang Chen.)

Vol.16  No.3
mCRPC Therapies: Choices and Questions
In 2004, docetaxel demonstrated a modest, yet meaningful survival and pain palliative benefit. Since then, we have seen the approval of sipuleucel-T, cabazitaxel, abiraterone, enzalutamide and radium-223 broaden the menu of agents that prolong overall survival in metastatic castration-resistant prostate cancer (mCRPC). Although each is moderately effective, none of these agents offer a cure and the biologic and clinical data to explain mechanisms of drug resistance remains scanty at best. As a result, the field must now rely on practical considerations, with much data extrapolation, to fuel logical utilization and sequencing of these therapies in hopes of achieving optimal patient outcomes. In this special issue, these new agents will be discussed thoroughly. This includes review of biologic mechanism of action, clinical efficacy and safety data, biomarkers and opinions on pragmatic use and combinations for future exploration. Although, the topics may be drug-focused, there is the inclusion of broad discussion on entire fields of therapy with historical and pre-clinical perspective. (Art by Xiang Chen)

Vol.16  No.2
Male androgen deficiency: a multisystem syndrome
Androgens have important effects on multiple organ systems which play critical roles in the regulation of a myriad of male sexual, somatic and behavioral functions critical to lifelong health. Androgen deficiency is a multi-system syndrome, presenting with typical clinical features in association with a confirmed low serum testosterone levels. This special supplement of the Asian Journal of Andrology is intended to reflect the complexity of male androgen deficiency disorders. It provides a critical update on many recent advances in clinical and experimental aspects of male androgen deficiency. A particular focus is on organ systems that, while not traditionally or directly associated with sexual or reproductive functions, critically contribute to male health over the life course. While this issue highlights progress in male health, many important current knowledge gaps and areas of controversies are also emphasised. In this vibrant field of research, many exciting opportunity remains for further research and therapeutic development towards improving men’s health and quality of life. (Art by Xiang Chen)

Vol.16  No.1
Male Reproductive Health and the Environment
Lessons from the occupational arena demonstrate the potential of industrial chemicals to damage human testicular function. An important but still unresolved question is whether low-level xenobiotic exposure of the general population poses a hazard. This special issue is addressed by a series of reviews on xenobiotic exposure profiles, possible biological mechanisms, research methods and knowledge on impact of specific exposures. Interdisciplinary research fields as gene-environment interaction and male-mediated developmental toxicity is also addressed. Papers are cross-linked by answers to questions mutually put forward by ten contributors. They consider the key issues about “Environmental Xenobiotics and Male Reproductive Health”. (Art by Xiang Chen)

Vol.15  No.6
Intratumour heterogeneity represents that the tumour lesion is composed of different tumour cells which play different roles in keeping the microenvironment of the tumour. The existence of intratumour heterogeneity affects the clinical intervention of the disease, thus raises the risk of disease-related mortality. Single-cell sequencing, as a newly developed technology, is widely used in tumour molecular biology and microbiology based on next generation sequencing. Like the different flowers and DNA double helix structure on the cover, single-cell sequencing is a scalpel to analyze the different functions of intratumoural cells, which increases the accuracy of early diagnosis, targeted treatment and prognosis prediction. (Art by Xiang Chen)

Vol.15  No.5
Proteomics strategies have been widely used in the field of male reproduction. For example, proteomes of human sperm and testis have been established. Bioinformatics is indispensable in the interpretation of high-throughput data from proteomics-based studies. It can help us understand the biology of spermatogenesis and also aid the discovery of potential biomarkers for male infertility. For example, with the help of bioinformatics, six novel cancer/testis genes can be identified based on human testis proteome. These genes could be candidate diagnostic biomarkers for cancers, as well as a valuable resource for the analysis of spermatogenesis. The cover image depicts the representative network of known cancer/testis genes in spermatogenesis and tumorigenesis. Bioinformatics can provide us with powerful connections between the proteomic data and the hidden biological significance. For more information, please refer to the review by Dr Zhou et al. on pages 594-602. (Art by Xiang Chen)

Vol.15  No.4
Androgen deprivation therapy (ADT) is widely used in the treatment of metastatic, recurrent and locally advanced prostate cancer. However, ADT, which leads to castrate testosterone level, is associated with numerous side effects, such as sexual dysfunction, osteoporosis, obesity and cardiovascular morbidity. Once the serum testosterone level recovers to normal range, ADT-related side effects will disappear gradually. In this issue, Dai et al (pages 466-470) found that in most clinically localized prostate cancer patients treated by surgery and subsequent short-term adjuvant ADT, serum testosterone can recover to normal range at 12 months after ADT cessation. Moreover, patients with higher baseline testosterone level need shorter time of testosterone normalization after ADT cessation. (Art by Xiang Chen)

Vol.15  No.3
Global Advances in Prostate Cancer Diagnosis and Therapy special issue
Global next-generation sequencing efforts have revealed the molecular landscape of prostate cancer to be rife with complexity. However, we are taking huge strides towards a more comprehensive understanding of this lethal disease, and increasing evidence suggests that genomic lesions frequently converge on specific cellular functions and signalling pathways. We are now entering an exciting era in prostate cancer research, where our vast array of sequence data can be exploited for diagnostic and therapeutic gain. Indeed, the cover image depicts significant molecular lesions in prostate cancer, several of which have the potential to affect patient treatment in the near term. For more information, please refer to the article by Dr Wyatt et al. on pages 301-308. (Art by Xiang Chen)

Vol.15  No.2
This special issue is directed towards the lessons learned since two publications in 1992 which prompted the most public, fervent and durable controversy in the short history of Andrology: the claims of world-wide falling sperm counts due to global pollution by industrial estrogenic chemicals. To this end, after the passage of two decades, we invited the progenitors of the controversy as well as range of experienced medical scientists familiar with the controversies to reflect on the lessons learned and offer their summations across a broad range of perspectives. Twelve contributors consider the key issues of whether there is any real decline in sperm counts, and, if there is, whether this has an impact on male fertility , and finally whether global oestrogen pollution causes any of these phenomena. (Art by Xiang Chen)

Vol.15  No.1
Surgeries in Andrology
This image on the cover is a parody of Rodin’s ‘‘Thinker’’. It is being used to represent the reluctance of men to seek medical attention, especially when the problem involves their genitalia. Recent advances in andrological surgeries make treatment of even the most challenging of these conditions more successful and less invasive than in times-past. In this context, we are pleased to present this 2013 Asian Journal of Andrology special issue focusing on "Surgeries in Andrology". This special issue is intended to provide a concise and substantive update for surgical treatment of conditions related to male sexual dysfunction and male fertility. (Art by Vanessa L. Dudley)

Vol.14  No.6
Col1a1, one of the subunit of collagen type I, belongs to extracellular matrix proteins which play a critical role in cellular proliferation and differentiation. However, the role of Col1a1 in the control of proliferation and differentiation of spermatogonial stem cells remains unknown. In this issue, Chen et al. (pages 842-849) explored effects of downregulation of Col1a1 on proliferation and differentiation of mouse spermatogonia. Their data suggest that decreasement of Col1a1 could suppress spermatogonia self-renewal and promote differentiation. In the cover illustration, whether spermatogonia differentiation occurs depends on the opening of blood-testis barrier (the faucet), which is regulated by a number of factors including the Col1a1 (the child in red?) and others (the child in black). These factors work together to either promote or suppress the spermatogonia differentiation, which ultimately leads to the dynamic equilibrium of spermatogonia proliferation and differentiation. (Art by Yiliang Wang.)

Vol.14  No.5
Bortezomib has been approved for the treatment of multiple myeloma, and is currently being investigated in other cancers. In this issue, Hu et al. (pages 695-702) demonstrated that bortezomib causes prostate cancer cells to up-regulate apoptosis-related mRNA as well as death receptors and down-regulate the MHC–I molecule on the cell surface. These data suggest that bortezomib can be used to sensitize prostate cancer cells to NK cell-mediated killing and improve current cancer therapies. This therapeutic strategy may be more effective in patients with androgen-independent prostate cancer. In the cover illustration, prostate cancer (middle) is very frightened because it will be killed by natural killer cells (left and right) soon through apoptotic pathway and others. Bortezomib may enhance immunotherapy for prostate cancer by decreasing the surface expression of MHC-I and increasing the surface expression of death receptors DR5 and Fas. (Art by Xiang Chen.)

Vol.14  No.4
The induced pluripotent stem (iPS) cells could have unlimited potentials to differentiate into various kinds of cell lineages for both regenerative and reproductive medicine. In this issue, Zhu et al. (pages 574-579) demonstrated that mouse iPS cells can be induced by retinoic acid to differentiate into spermatogonial stem cells (SSCs) in vitro and that SSCs can further develop and become spermatogonia and eventually round spermatids in vivo when they are transplanted into recipient testes of infertile mice. The cover photograph illustrates the approaches and the generation of spermatids from mouse iPS cells. Art by Xiang Chen.

Vol.14  No.3
Special Issue on Differenntiation of Lethal and Non-Lethal Prostate Cancer
Although the introduction of serum prostate-specific antigen (PSA) in the 1980s has dramatically altered and benefited the initial diagnosis of prostate cancer, the widespread use of PSA testing resulted in overdetection and overtreatment of potentially indolent disease. Thus, a clinical dilemma today in the management of prostate cancer is to discern men with aggressive disease who need definitive treatment from men whose disease are not lethal. The goal of this AJA special issue is to determine if there are tools that can provide additional discrimination to the currently utilized clinical tools to identify those with the forms of prostate cancer most appropriate for a program such as active surveillance and those that will perhaps benefit for more aggressive therapeutic approaches. Basic and clinical scientists discuss current and future approaches to improve the health outcomes of men who are diagnosed with prostate cancer. A majority focuses on novel molecular approaches for the discrimination of lethal prostate cancer, for example, ETS gene rearrangements, CTAs, Cyr61, BRCA2 and genetic predisposition.

Vol.14  No.2
Special Section on the Complications of Androgen Deprivation Therapy
Prostate cancer is one of the most common malignancies in men worldwide. Androgen deprivation therapy (ADT) is widely used in the treatment of locally advanced and metastatic prostate cancer. Its use has increased over the past decade as patients with localized cancer and with biochemical recurrences are also being treated with ADT. While efficacious in a subset of patients, ADT is associated with many adverse effects such as sexual dysfunction, decreased muscle mass and strength, increased fat mass, osteoporosis, gynecomastia, memory changes and vasomotor symptoms. Recently, metabolic derangements, coronary artery disease and cardiovascular mortality have also emerged as adverse effects of ADT. This volume contains articles from renowned experts on the indications and adverse effects of ADT. In this special supplement, in addition to summarizing the indications of ADT, the leading experts have contributed on the following adverse effects of ADT: metabolic and cardiovascular, body composition, hematological, cognitive, vasomotor, quality of life and sexual. Given the large number of men on ADT, it is important that both patients and the physicians are cognizant of these adverse effects.

Vol.14  No.1
Special Issue on Clinical Male Infertility
Clinical Male Infertility Clinical evaluation of the infertile man is an essential skill in reproductive medicine, with male factors being involved in half of all infertile unions. Accurate diagnosis may allow specific treatments to restore natural fertility and/or identify serious medical conditions more prevalent tin infertile men, such as androgen or gonadotropin deficiency or testicular cancer. This volume contains articles by leading experts on the clinical and laboratory evaluation of infertile men along with background on the pathophysiology of the diverse causations of male infertility. For men for whom specific treatments are not available assisted reproductive treatments, especially intracytoplasmic sperm injection, provide a powerful means to bypass their disability leading to the birth of their own offspring. The emerging science about the environmental and genetic basis of spermatogenic failure is considered along with the implications for ARTconceived offspring. Finally the impact of infertility on couple and male partner is also considered.

Vol.13  No.6
Prostate cancer (PCa) has become the most common malignancy that affects elderly men. Interestingly, PCa occurs predominantly in the peripheral zone (PZ) rather than transition zone (TZ). The mechanisms underlying this phenomenon are largely unknown. In the article of Jiang et al. on pages 798-805, utilizing prostate stromal cells derived from the peripheral zone (PZsc) and the transition zone (TZsc), they found that PZsc provide better stromal microenviroments than TZsc by secreting growth factors, and PZsc have a greater capacity to induce PCa development and progression than TZsc via growth factors regulated by sex hormones. Therefore, targeting stroma in PZ may aid the search for novel prevention and therapeutic strategies for PCa.

Vol.13  No.5
Di-n-butyl phthalate (DBP) is an industrial chemical used primarily as plasticizers and is present in a wide variety of products in our daily life, including building materials, medical devices, and particularly food packaging. In the article of Bao et al. on pages 702-709, when male rats were treated with low doses of DBP which are similar to environmental exposure doses, the expression levels of proteins participating in spermatogenesis have changed although no obvious morphological changes appeared. So it is also an endocrine-disrupting chemical that has the potential to affect male reproduction. Therefore, now whether to add DBP in these industrial products, and whether to use these products in male daily life really are the questions. For more information, please refer to the article of Prof. Sha JH et al. on pages 702-709

Vol.13  No.4
Asian Men Health
The seed for the development of men9s health in Asia was sowed about 10 years ago. This nascent ‘germination’ has certainly grown into a small, but healthy and luxuriant ‘shrub’. The miniature canopy of variant colours signifies the diversed development of men9s health status in Asia. The time is right to plant a strong and deep foundation in the field of men9s health in Asia. With the widespread interest in men9s health issues among the ever enlarging stakeholders, it is our hope and believe that the growth of men9s health development is poised to flourish into a strong unshakable discipline (tree) of medicine. For more information, please refer to the article of Prof. Zhu JC et al. on pages 512-518.

Vol.13  No.3
Although a number of genes are known to be involved in spermatogenesis, only a few possess clean-cut arrest phenotypes indicative of their role in global regulation of key spermatogenic steps. LM23 is a gene with testis-specific expression in Rattus norvegicus. The LM23 knock down testes contained germ cells arrested at the spermatocyte stage. LM23 may regulate the G1/S and G2/M transition of the cell cycle. Both Fas-FasL pathway and the mitochondrial pathway may be activated for the down-regulation of LM23. LM23 may be important to both the life and death of the spermatogenic cell. For more information, please refer to the article by Dr Cheng et al. on pages 446-452.

Vol.13  No.2
Currently, docetaxel-based combination chemotherapy remains the predominant modality for castration-resistant prostate cancer. However, taxane-related drug resistance and neurotoxicity limit its clinical utility. The mitotic kinesin-5 motor protein Eg5, which plays a critical role in bipolar spindle formation and duplicated chromosome separation during the early phase of mitosis, has emerged as an attractive target for cancer chemotherapy because inhibition of Eg5 can arrest dividing cells in mitosis followed by cell death, without affecting the function of interphase microtubules. A novel Eg5 inhibitor, S-(methoxytrityl)-L-cysteine [S(MeO)TLC], its potent anticancer efficacy was assessed in prostate cancer both in vitro and in vivo in the article of Dr Xing et al. on pages 236-241.

Vol.13  No.1
Special Issue on Cell Biology and Genetics of Sperm
The cover picture depicts a cryostat section of mouse testis treated with lucigenin, NADH (nicotinamide adenine dinucleotide) and ethidium bromide. Under these conditions the lucigenin probe localizes to the mitochondria and generates a striking image of the mitochondrial gyres as they are assembled in differentiating spermatozoa within the germinal epithelium (Joel Thogersen and John Aitken, unpublished observations). The mitochondria are the major source of free radicals in spermatozoa and via this mechanism make a significant contribution to oxidative stress in these cells as described in the Chapter by Aitken and Koppers (see pages 36-42).

Vol.12  No.6
Because the androgen-signaling pathway is integral in prostate cancer progression, to gain beneficial effects when managing high risk prostate cancer, androgen deprivation therapy has been highlighted as an optimal systemic modality. Results from several randomized clinical trials have already showed that the combination of radiotherapy and androgen deprivation therapy consistently results in improved disease-free survival and in a decreased biochemical recurrence rate. As an integrated approach combining local therapy and systemic treatment, prolonged androgen deprivation with cryoablation may also lead to a synergistic effect, providing a wider therapeutic territory over that which has been directly affected by cryoablation, especially for high risk patients in whom systemic disease is likely. For more information, please refer to the article by Ko et al. on pages 827-834.

Vol.12  No.5
Recently, a few of RING finger proteins have been reported to be E3 ubiquitin-protein ligases exclusively present in the testis tissue and play important roles in the process of sperm production and qualitycontrol. ZNF645, a novel RING finger protein, is identified to be exclusively expressed in normal human testicular tissue, present in Leydig cells, spermatocytes, and the postacrosomal perinuclear theca region & the entire tail of sperm. ZNF645 contains a C3HC4 RING finger domain, a C2H2 zinc-finger domain, and a proline-rich region, and might be an E3 ubiquitin ligase. For more information, please refer to the article of Dr. Liu et al. on pages 658-666.

Vol.12  No.4
Since time immemorial, plants have been used as valuable and safe natural source of medicines across various civilizations. The healing abilities of wide majority of plants could be ascribed to the pharmacological principles present in them. Plants have a long folklore in aiding fertility. On the other hand, several commonly used plants are known to impair male reproductive functions. The toxicological attributes of various commonly used plants could be due to their effects on various cell types in the testes leading to impaired spermatogenesis and steroidogenesis. From the reproductive standpoint, plants could be rightly described as a double-edged sword. For more information, please refer to the article of Prof. D’Cruz et al. on pages 468-479

Vol.12  No.3
Currently, there are only two clinically approved and effective methods of male contraception, condoms and vasectomy. Each method has drawbacks. Condoms provide protection against sexually-transmitted disease, but are intrusive and associated with a relatively high rate of unintended pregnancy. Vasectomy is highly effective, but is difficult to reverse and may lead to chronic testicular discomfort. Newer approaches to male contraception as well as optimization of existing contraceptive approaches such as vasectomy are needed to prevent unintended pregnancy. For more information, please refer to the article of Professor Amory et al. on pages 315-321.

Vol.12  No.2
With the release of the latest edition of the World Health Organization (WHO) Laboratory Manual for the Examination and Processing of Human Semen (5th edition), Asian Journal of Andrology (AJA) is pleased to present this special issue on "Semen Analysis in 21st Century Medicine" which launches into a sometimes incendiary debate surrounding the recommendations and guidelines for quality control and interpretation set down in the manual. We are honored to invite Prof David J Handelsman and Prof. Trevor G Cooper to be the guest-editors. The purpose of the collection is to discuss some of the behind the scenes controversies, many of which continue, including the origins, utility and specific applications of population reference ranges for semen analysis, problems with modern morphological methodology and the possibility and limitations using semen analysis in population or clinical research studies beyond the original uses for male infertility evaluation. It is our sincere hope that perspectives in this issue will educate readers to approach the new WHO manual with a realistic and critical appreciation of the balance its recommendations represent. In short, we are very excited to present this outstanding collection, and would like to thank two guest-editors and all of our authors for their contributions and support to AJA. We wish the readers a happy and productive New Year and please sit back and enjoy this Special Issue!

Vol.9  No.4
The Fourth Epididymis (Epid IV) Workshop was held between December 4th and 7th 2006 in Chatel-Guyon, France. This was the first European venue for these workshops following Epid III held in Charlottesville, Virginia, USA in 2002, Epid II held in Newcastle, Australia in 1998 and a one-day meeting (later named Epid I) in Hong Kong, China in 1992. The 2006 meeting was organised by Drs Jo雔 R. Drevet (Aubi鑢e, France) and Trevor G. Cooper (M黱ster, Germany) and was a satellite meeting of the Fourth European Congress of Andrology (ECA2006) which followed in Toulouse (France) from December 8th to 10th. Epid IV was attended by 90 basic science researchers from 14 countries. The hotel accommodation was adjacent to the meeting hall and the meeting proved an equal distraction to the lure of the Casino in the same building! Posters were viewed from the beginning to the end of the workshop and frequent coffee breaks were organised among them to facilitate scientific exchange. In these hospitable conditions old acquaintances were revived and new friendships made. The meeting started with an introductory lecture given by Russell Jones (Newcastle, Australia) on comparative epididymology and was followed by 8 sessions of 4 to 5 presentations each (see the programme below for a detailed list of speakers) in which various aspects of epididymal physiology were covered: sperm maturation and storage, cellular and gene expression activities of the epididymal epithelium, recent advances in global approaches of the epididymal transcriptome and proteome as well as the presentation of some putative epididymal contraceptive targets. The last session of the programme was devoted to research carried out on the human epididymis and most of the speakers in this session were also invited speakers at the ECA2006 meeting. A session was also devoted to presentations given by young investigators who were selected from the 36 poster abstracts received. The final lecture was given by David Hamilton (Mineapolis, MA, USA) on December 7th. As he could not attend the meeting, he provided it as a video presentation. His talk entitled 揟he ~Omes are coming!?illustrated what, from his point of view, would be epididymal research in the 21st century. During the meeting the site of the next epididymis workshop was discussed. Drs P. S. Cuasnic?(Argentina) and M. C. W. Avellar (Brazil) stepped forward to propose the idea that South America could host the next Epididymis workshop in 2010. Most of the speakers agreed to produce a manuscript of their presentations that are collected in this Special Issue of the Asian Journal of Andrology.
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