Journal Of Andrology Research Articles

Reproductive health problems: genetics vs. environment

Reproductive health problems: genetics vs. environment

Clinical Male Infertility and Assisted Reproduction

The current issue of Journal of Andrology is designated as a Special Issue on Clinical Male Infertility and Assisted Reproduction. The opportunity to create a Special Issue developed because of a high number of quality papers that were recently accepted for publication. Highlighting these papers with a Special Issue is an opportunity to capitalize on the purposeful goal of the Journal to solicit high quality papers in basic and clinical Andrology, emphasizing genetic aspects of Andrology and assisted reproduction. Encompassed in the focus on clinical genetics, we have included manuscripts in this issue that examine the relationship between varicocele and DNA integrity (Enciso et al) as well as varicoceles and sperm aneuploidy (Baccetti et al). Although DNA integrity and sperm aneuploidy appear more common in men with varicoceles, it is not clear whether it is the physical condition of varicocele, or merely poor sperm production that result in these sperm DNA abnormalities. Different approaches to evaluation of sperm DNA integrity were compared in a paper from the Utah group (Chohan et al). This is an important topic because of increasing attention being drawn to DNA integrity and its ability to detect male factor contributions to infertility. Other studies on clinical genetics included a report on the frequency of androgen receptor mutations in Indian men (Singh et al) and further investigation of the genetic anomalies that are present in men with globozoospermia (Christensen et al). This article is complemented by the paper from Emilia et al, also investigating chromosome abnormalities in men with large heads or multiple tails. Too often, treatment of patients with globozoospermia and other phenotypically-identifiable conditions is undertaken using assisted reproduction without any consideration of the potential underlying genetic anomalies. A study from Chen et al reported on the inverse relationship between sperm apoptosis and sperm motility in infertile men. Kovacic reported on the value of pentoxifylline stimulation prior to use of sperm for assisted reproduction, a useful clinical tool to help identify viable sperm among a population of immotile spermatozoa. Several articles examined technical issues relating to sperm retrieval and assisted reproduction. Given the increasing role of andrologists in assisted reproduction, these articles are worthy of note. Hauser et al compared sperm extraction (TESE) with testicular aspiration, and Wald et al reported on outcomes using frozen or fresh testicular sperm from men with nonobstructive azoospermia used for ICSI. The discussions from Androlog outline a current area of controversy regarding the relative value of assisted reproduction versus specific treatment of male infertility (vasectomy reversal). Nistal et al described five patients with Wolffian-derived intratesticular abnormalities; given the increased potential for detection of small and benign lesions within the testis, a greater understanding of rare intratesticular lesions is worthwhile. More information on alpha-glucosidase activity in human semen was presented by Schill et al. Whereas clinical evaluation of glucosidase activity is not a standard in the United States, its application in Europe is far more common. Other insight into clinical topics is provided in the articles by Shafik et al and Corona et al describing specific aspects of ejaculatory and sexual function. Haugen et al described the characteristics of semen parameters in a group of fertile men from Norway. Amory et al provide further information on the use of oral androgen supplementation (testosterone in oil) in combination with 5-alpha reductase inhibitors. Such a combination provides promise as treatment of men with androgen deficiency, enhancing circulating testosterone levels while limiting their effects on the prostate. A breakthrough article is included in this Special Issue, outlining the important antifertility effects of DDT on men. Although DDT is not used in the United States any longer, effects on fertility may still be seen in other countries, particularly in Africa where it is still in use, and concern about its metabolic products may exist long after popular use is stopped (De Jager et al). Taken together, these articles reflect an increase in the high quality articles that we have been receiving at the Journal—we hope our readers agree with our reviewers and the editors in their appraisal of these articles.

CITATION ANALYSIS OF FIVE JOURNALS IN ANDROLOGY

To find out features in literature demand by researchers in the field of andrology and to offer advice on literature utilization and journal management. Five andrology journals indexed by Science Citation Index Expanded (SCI-E) (Andrologia, Archives of Andrology, Asian Journal of Andrology, International Journal of Andrology, and Journal of Andrology) were included in the study. Original articles, editorials, reviews, corrections and letters from these journals were analyzed with bibliometric method for document loading, citations, information absorbing ability, and geographical coverage. The average number of references in each paper was 28.78. The main type of references was periodicals (94.32%), while books and other sources accounted for only 5.68%. Average Price index was 30.14%. The number of references in the first ranking 10 periodicals cited by the five journals made up 34.53% of the total references cited. Geographically, the five journals covered 6 continents with 42 countries or regions. Andrology journals have a wide coverage of literatures, which are related to reproductive medicine, urology, endocrinology and biochemistry. References in andrology journals are mainly periodicals and are relatively old. US, China and Japan lead the world in andrology researches for the number of papers published.

Specialty Spotlight: Urology

Life experience, whether it is a former life as a technician or a family member's illness, generally influences the specialty area future physicians choose when it comes time for a residency. My exposure and interest in urology came by way of my previous career as a medical journalist working for the Journal of Andrology. The 2 years that I spent working in urology and andrology piqued my interest in a possible career choice as I now enter my second year of medical school. Urology, also known as genitourinary surgery, is a surgical subspecialty that tackles a wide spectrum of disease involving the male and female urinary tracts and the male reproductive system. The field of urology has long been a desirable specialty, attracting some of the most competitive medical students, according to the Society of Women in Urology. For Dr Cathy K. Naughton, assistant professor of Urology at the Washington University School of Medicine, she credits her interest in urology to three factors: exposure to the field, process of elimination, and role models. “It takes one person to spark your interest in something,” Naughton said. “Mentorship is key.” Relating to the people in the field is just one of the many reasons to pursue a career in urology. The broad range of surgeries performed, the lifestyle, research and technology, specialization, and flexibility within urology are some other factors that make the field attractive. People going into surgical fields generally mention qualities like enjoying working with their hands and valuing team-work. Having a strong interest in surgery is one of the most important reasons to enter into urology. For medical students interested in urology, Dr Peter Schlegel, chairman of the Department of Urology at the Weill Medical College of Cornell University offers this piece of advice: “Learn as much about the field from residents, other students who have applied for residency positions, and local faculty members.” Participation in a urology rotation is also important to gain exposure to the field. According to Schlegel, many students take more than 1 month of urology subinternship, but he also notes that it is not necessary for interview or residency preparation. If all this exposure to the field has confirmed the decision to pursue urology, some other areas of the potential application should be considered. According to both Naughton and Schlegel, a well-rounded applicant who expresses interest in urology through clinical, research, or apprentice-based experience is critical. The importance of research is dependent on the program. The more academic programs will be interested in research but do not necessarily require that the research be in the field of urology. For Osteopathic medical students interested in urology, the American College of Osteopathic Surgeons requires that a resident with a surgical specialty develop a research project and follow through with it, ending with a paper suitable for publication, according to Dr Al DePolo, Jr, program director for the Department of Urology at the Michigan State University College of Osteopathic Medicine. Although many factors are taken into consideration when deciding between applicants for a coveted residency spot, DePolo cites some qualities that go beyond class-room performance, rotations, and research. “I think the best things a prospective candidate can bring to any residency are: a strong desire to learn, a good work ethic, honesty, a sense of fair play, and the willingness to be part of a team,” Depolo said. According to statistics released by the National Residency Match Program for 2005, 108 nonmilitary accredited urology residency programs in the United States listed 232 positions, with all vacancies being matched. Medical student applicants, totaling 347, submitted preference lists netting 115 unmatched applicants, giving a 78% match rate. Although there are many reasons to choose urology and many people who have decided on urology as their career of choice, not everyone follows this path. Trainees might not select this specialty because surgery is not for everyone and because surgical training can oftentimes be brutal. In addition, future Urologists need to be comfortable with the topic material and with the reality that urology is a male-dominated field. Despite this, it is important to remember, as Dr Schlegel points out, that women with an interest in urology are often viewed favorably because they have been “underrepresented in the field in the past.” With all this information to digest, I know I will follow a wise piece of advice cited by DePolo: “Do not become set in your choice too early. Take the time and the effort to experience other areas of medicine and surgical sub-specialties. A decision about a career area can wait until the third year.” And you never know, after all is said and done and I have followed the advice of all, urology might just be in my future.

Introduction

A multidisciplinary international course on Male Erectile and Sexual Dysfunction, organized on behalf of the Educational Committee of the European Academy of Andrology, convened in Rome at the end of 2004. The goal of the meeting was increased interactions among peers leading to discussion of the latest pathophysiological and clinical efforts specifically related to male sexual function and dysfunction. All podium presenters were invited to submit manuscript to the official journal of the Academy, the International Journal of Andrology. The Editor-in-Chief, Prof. Jorma Toppari asked us to serve as Associate Editors of this Supplement, following the rules and the peer-review process of the Journal's tradition. As can seen from the size and the content of this IJA supplement, there was an overwhelming response to our invitation. In the past few years, from the marketing of the first efficacious oral treatments for erectile dysfunction, thousand of scientific articles, books, textbooks, monographies have been published on the field of male sexual medicine, which is definitively an important, if not that with the greater growth's impetus, of Andrology. However, because of this scientific ‘overgrowth’, it seems necessary to point out with timely and authoritative scholarly review articles a so complex matter. In fact, the development of male medical sexology in many medical, such as endocrinology, psychiatry, internal medicine, and surgical specialties, such as urology, calls for closer integration. Andrology, with the help of basic science, born as a multidisciplinary discipline to overcome the separation between specializations and subspecializations, which deprives patients of a holistic approach to their sexual difficulties. We hope that by providing an expanded base of literature, this Supplement will stimulate more sexological culture, further research efforts, new data to support innovative diagnostic procedures and treatment options for men with sexual medical concerns. Male sexual function and dysfunction are here dissected and up-to-date review articles describe the neuroendocrine regulation of male libido, flow charts for diagnosing premature ejaculation and vascular, endocrine, and neurogenic impotence. A particular emphasis has been used in the therapy section, giving to the reader a practical approach to the use of short-acting type-5 phosphodiesterase inhibitors, of the new long-acting as well as psychotherapy. We owe special thanks to Prof. Toppari, to the Editorial Assistant of the IJA, Ms Leena Karlsson, and to Educational Committee of the EAA for their kind offer, as well as their encouragement and support for this important scientific project. Furthermore, we are in debt with Lilly Italia and to the manager Dr Concetto Vasta for the generous and unrestricted grant which made possible this publication. We also would like to personally thank the Authors for their hard work to submit their manuscripts in a timely fashion. Sir Francis Bacon wrote in his De dignitate et augmentis scientiarum (Advancement and Proficiency of Learning) that ‘Scientia et potentia humana in idem coincidunt’, a notable sentence that can be freely translated as ‘Science and (sexual) human potency exactly coincide’. And this is our arrivederci to the reader of this IJA’ Supplement on Male Erectile and Sexual Dysfunction.

Putting the Brakes on Renin Release

Modulation of renin release from juxtaglomerular cells is critical for appropriate adjustments of the cardiovascular and renal systems to internal and external stresses, and dysregulation of renin release participates in the pathophysiology of hypertension, vascular disease, heart failure, and chronic renal disease. This justifies investments in research to elucidate the fundamental mechanisms regulating renin release. These investments have yielded, and continue to yield, high returns, as exemplified by Schweda et al1 in this issue of Hypertension , showing that A1 receptors mediate high perfusion pressure–induced inhibition of renin release, whereas prostaglandins (PGs) participate in low perfusion pressure–mediated stimulation of renin release. The purpose of this commentary is to discuss how Schweda et al’s findings confirm and challenge present-day models of renin release. As comprehensively reviewed by Davis and Freeman2 and Keeton and Campbell,3 investigators recognized early on that three systems, namely the sympathetic nervous system, the macula densa apparatus, and the intrarenal baroreceptor, are the primary physiological mechanisms regulating renin release from juxtaglomerular cells. A key development was the recognition that the two most important biochemical accelerators of renin release are catecholamines (mediating sympathetically induced renin release) and PGI2 (mediating macula densa–induced and intrarenal baroreceptor–stimulated renin release).4 Subsequently, a third autocoid, adenosine (acting via A1 receptors), was proposed to serve as a molecular brake on renin release and thereby to moderate the effects of catecholamines and PGI2 on renin secretion.5 Because cAMP is a critical second messenger mediating the exocytosis of renin from juxtaglomerular cells, adenylyl cyclase unifies these concepts because β-adrenoceptors and PGI2 receptors accelerate, whereas A1 receptors brake the rate of cAMP production. The results reported by Schweda et al corroborate the accelerator/brake model of renin release because they report that PGs mediate stimulation of renin release …

Editorial Commentary

Editorial Commentary

Andrology: Pursuit of the Scientific Trinity

It is a great honor to accept the opportunity to serve the American Society of Andrology and the Journal of Andrology as the new Section Editor of the Journal of Andrology Lab Corner. Previous section editors have served the Journal extremely well, and I will strive to do so also. I would first like to thank the Co-Editors-in-Chief, Drs Matthew Hardy and Peter Schlegel, for this privilege. Within this brief editorial, I will take the occasion to 1) introduce myself, 2) provide a philosophical view of the Journal of Andrology Lab Corner focus during upcoming months, 3) provide a schematic vision for manuscript submission and review, and last, 4) implore you, the individuals of the Andrological Society, to share ideas and manuscripts that will serve our readers well. As a graduate student, I was fortunate to be mentored in Reproductive Biology and Endocrinology by Drs Fredrick Stormshak and Jerry Reeves at Oregon State and Washington State Universities, respectively. These individuals made great impressions on me in areas of scientific imagination, rigor, experimental design, and the use of statistical analytical tools. After my doctoral training, I found myself at a crossroad, desiring a quest for scientific knowledge and also the ability to translate these findings to practices that would impact patient care. Quite serendipitously, the opportunity arose to conduct a postdoctoral fellowship with Dr Donald P. Wolf at the Oregon Regional Primate Research Center. This amazing experience profoundly molded my passion for basic science studies of gamete and embryo biology with an emphasis on assisted reproductive technologies (ART). At comple-

Native specific activity of glutathione peroxidase (GPx‐1), phospholipid hydroperoxide glutathione peroxidase (PHGPx) and glutathione reductase (GR) does not differ between normo‐ and hypomotile human sperm samples

Native specific activity of glutathione peroxidase (GPx‐1), phospholipid hydroperoxide glutathione peroxidase (PHGPx) and glutathione reductase (GR) does not differ between normo‐ and hypomotile human sperm samples

Native specific activity of glutathione peroxidase (GPx‐1), phospholipid hydroperoxide glutathione peroxidase (PHGPx) and glutathione reductase (GR) does not differ between normo‐ and hypomotile human sperm samples–Authors' Reply

Dear Sir, Thank you for giving us the opportunity to answer the questions raised by Ursini and Maiorino on our paper ‘Native specific activity of glutathione peroxidase (GPx-1), phospholipid hydroperoxide glutathione peroxidase (PHGPx) and glutathione reductase (GR) does not differ between normo and hypomotile human sperm samples’ by Tramer et al., published in International Journal of Andrology (27: 88–93, 2004). The major objections put forward concern the evaluation of the PHGPx enzymatic activity and of the protein content. A premise, necessary, however, as already discussed in our paper, concerns the substantial difference between the specimens under scrutiny in the two laboratories: the whole human sperm ejaculate pellet treated with chaotropic agent and GSH (Ursini's laboratory), and intact, Percoll-purified human sperm cells, in the presence of desferal and resveratrol as antiperoxidants (our laboratory). The points (1), (2) and (3) state that our measurements of GPx-1 and PHGPx are invalidated both by blank management as well as by the volume of the reaction mixture. In all cases we have subtracted the slopes of the blanks, comprehensive of non-enzymatic substrate reduction, and evaluated the native enzymatic activities (accessible after sonication and in the presence of Triton X-100), on the basis of at least 10 min kinetics, which allows readings on slopes higher than the instrument noise and sensitivity (computer-assisted Beckman DU 640; volume assay 1.5 mL). It is hard to envisage our data in a frame of a background measurement. On several occasions (Tramer et al., 1998, 2002) we in fact evaluated sperm PHGPx activities which consistently differ, for example, on the basis of the kind of epididymal sperm cells we examined. We reported also native PHGPx activity in sperm cell subfractions, where very different specific activities were obtained (Godeas et al., 1997). Imai et al. (2001) and Imai & Nakagawa (2003) also reported native PHGPx assay in sonicated human sperm cells. We are aware, on the contrary, that PHGPx reacts also with tert-butylhydroperoxide as substrate, but this activity is one order of magnitude lower than that measured by using the specific substrate phosphatidylcholinehydroperoxide (PCOOH) in the presence of Triton X-100 (Ursini et al., 1985). Our value for GPx-1 can therefore be ascribed to PHGPx only in minimal part. This, anyway, does not change our results concerning this enzyme, which, likewise to glutathione reductase (GR), has already been evaluated by other authors in human sperm cells (Alvarez & Storey, 1989; Griveau et al., 1995; Storey et al., 1998). The question of protein determination is more subtle, mainly because we have to compare two apparently similar methods: the Lowry one in the case of Ursini's laboratory, and the bicinchoninic one in our case. The Lowry approach is more prone to interference with many media reagents, rendering it very difficult to prepare a suitable blank. The value of 1 mg protein corresponding to about 108 sperm cells we obtain may therefore not be considered tout court extremely low. The comparison between our evaluation of specific activities (nmoles/min×106 cells) and those of Ursini's group (nmoles/min mg solubilized protein), although possibly approximate, also on the basis of different temperature assay, does not in any way dismantle the main output of our data: the effective lack of relationship we find between all the three activities and sperm cell motility from a statistical point of view. In conclusion, we feel therefore that the discrepancies raised by the comparison of the two sets of results are only apparent. The two approaches must be viewed in their own contexts, which are inherently different. We have in fact considered the native activity of three enzymes from the point of view of their condition as much possible near to the physiological status of the sperm cell. Ursini's group has monitored the variations of an enzymatic activity after its in vitro reconstitution. These are therefore two approaches, not exactly superimposable, which indeed co-exist, giving two kinds of evidence. We feel finally that the protein expression of the enzyme(s) will be a necessary complement to the whole picture. Imai et al. (2001) have in fact recently reported on this, as we discussed in our paper.

The 25th Volume: Early Years of theJournal of Andrology

The 25th Volume: Early Years of the<i>Journal of Andrology</i>

Phthalate Exposure and Early Thelarche

Phthalate Exposure and Early Thelarche

The 25th Volume: Did You See the Latest?

The Journal of Andrology is now completing its second year online, and the shift to electronic access has been a successful ongoing venture for the American Society of Andrology. The Society wisely chose to facilitate desktop availability of the Journal, selecting HighWire as its electronic publisher. The availability of electronic publication is an important factor for the continued visibility of our Journal. If you have not done so already, directing your Web browser to the URL, http:www.andrologyjournal.com, will bring the Journal's content to your screen in a few mouse clicks. Many readers have become accustomed to reading and printing out each issue's content from their desktop computers. Some of you have even activated “ETOC,” the free electronic table of contents feature that automatically provides an early notice of each Journal issue by e-mail. The URL for ETOC is http:www.andrologyjournal.orgsubscriptionsetoc.shtml. Typically, each online issue of the Journal is posted 2 weeks before the paper version arrives in the mail. Therefore, the online era brings not only increased convenience but also greater speed. Within the Journal's editorial office, we have also increased our use of electronic communication to speed transport of manuscripts to reviewers, allowing an efficient review process and making submission of articles to the Journal of Andrology more attractive. The editors are committed to further enhancement of the Journal's impact within the andrology community and beyond. Rapid publication of accepted manuscripts, complete electronic archiving through the first volume, and key-word tracking by e-mail are just a few of the extra services readers may see in the years ahead. We will keep you posted.

Trainee Page

Welcome to the first installation of the Trainee Page in the Journal of Andrology. The American Society of Andrology (ASA) currently has 91 trainee members. A trainee is defined as a person in training interested in the progress and development of andrology such as graduate students, postdoctoral fellows, medical and veterinary students, medical residents, and fellows. We at the ASA and the Journal understand and acknowledge that the future of the society as well as the science lies with the trainees, and it is with that knowledge that we are proud to introduce this new section. At this time, trainee membership to the society includes a free subscription to the Journal of Andrology and reduced registration fees for the annual meeting, postgraduate course, and laboratory workshop. It also provides access to an on-line members-only section and access to Androlog, the on-line forum to discuss the latest issues and topics in the field of andrology. Trainee members are also eligible for travel grants and presentation awards. And it goes without saying that membership provides the opportunity to interact with your peers and the most accomplished scientists in andrology. With the advent of this new section, we hope to expand the benefits provided to the trainee. With the use of this section, we look forward to highlighting concerns of trainees such as help and guidance when it comes to the job search, strategies for interviewing, and preparing resumes/curriculum vitaes as well as some how-to pieces focusing on grant writing and preparing a scientific article and what to look for as a reviewer. We would also like to provide them with some basic information like typical starting salaries for someone in academia as opposed to a private lab, for example. Another interesting item to look for on this page will be a series entitled, “Careers in Andrology.” This will be an up-close-and-personal profile of different career paths that one can pursue after his/her training. In the future, we will look into other ideas to evolve this section and the attitude of the society toward trainees. We hope to be able to offer a link in which students can find out about prospective employment opportunities. As we celebrate the 25th anniversary of the Journal, it is an exciting time to be a trainee in the field, and we at the ASA and the Journal will do our best to prepare you to join the ranks of esteemed colleagues. To become connected and take advantage of these exciting opportunities and new benefits, you need to become a member. And as for this page, stay tuned. We hope you will enjoy the exciting road ahead for the Trainee Page.

Synopsis: 2003 Annual Meeting of the American Society of Andrology.

Synopsis: 2003 Annual Meeting of the American Society of Andrology.

EAA Prizes &amp; New Editorial Board for the International Journal of Andrology

EAA Prizes &amp; New Editorial Board for the <i>International Journal of Andrology</i>

Exposure to Phthalate Esters

Exposure to Phthalate Esters

Human Exposure Estimates for Phthalates

Human Exposure Estimates for Phthalates

News from the european academy of andrology addendum to the supplement of the international journal of andrology, volume 22, supplement 1, 1999

News from the european academy of andrology addendum to the supplement of the international journal of andrology, volume 22, supplement 1, 1999

Increased testosterone production in vitro by Leydig cells from rats with severe autoimmune orchitis.

We have previously observed (M. O. Suescun et al., 1994, Journal of Andrology, 15, 442-448) that rats with autoimmune orchitis (EAO) exhibit increased testosterone production in vitro by isolated testes. The aim of the present study was to determine whether the increase in testosterone production correlated with an enhanced number of Leydig cells and/or enhanced steroidogenic capacity per Leydig cell. For this purpose, EAO was induced in adult Sprague-Dawley rats by active immunization with testicular homogenate and adjuvants. At 80 days after the primary immunization, 60% of rats presented with severe testicular damage characterized by sloughing of the seminiferous epithelium, seminiferous tubule atrophy and interstitial mononuclear cell infiltration. At 160 days after the first immunization, testicular lesions were more severe. A morphometric study, by light microscopy, showed an increase in the number of Leydig cells in rats with EAO (45% increase at 80 days and 50% at 160 days). By electronmicroscopy, testicular sections of rats with EAO revealed the presence of numerous Leydig cells closely associated with macrophages. Most Leydig cells exhibited ultrastructural features of active steroid secreting cells. The steroidogenic capacity of Percoll-purified Leydig cells from tests of rats with EAO, killed at 80 and 160 days, was evaluated. Leydig cells from rats with EAO exhibited an enhanced steroidogenic response to hCG in vitro at 80 days (38%) and an increase in basal (77%) and post-hCG testosterone production (115%) at 160 days compared to controls. However, these cells were less sensitive to hCG. In conclusion, the results indicate that the enhancement of in-vitro testosterone production observed in rats with EAO is accounted for both by the increased number of Leydig cells and by the increased testosterone production of each Leydig cell.