In this study, we investigated the safety and feasibility of glans-preserving surgery for superficial penile squamous cell carcinoma. Young patients with penile primary tumors exhibiting favorable histologic features wer...In this study, we investigated the safety and feasibility of glans-preserving surgery for superficial penile squamous cell carcinoma. Young patients with penile primary tumors exhibiting favorable histologic features were best suited for organ-sparing procedures, enabling them to avoid sexual disturbances. The study included 12 patients, 38-53 years of age (median age 46 years), with superficial lesions involving the glans penis, coronary sulcus, or shaft skin. After clinical staging and grading, those patients were offered a glans-preserving procedure to preserve the normal appearance and functional integrity of the glans penis. Of the 12 patients referred, the tumors were TaG1 in 4 patients, TaG2 in 3, TisG1 in 1, TisG2 in 1, T1G1 in 2, and T1G2 in 1. All patients returned to normal sexual activity 1 month postoperatively. Sexual function and sexual satisfaction were well maintained after surgery. The cosmetic results were considered satisfying/very satisfying by 83% (10 of 12 patients). Follow-up data were available on 12 patients at a mean follow-up of 62.5 months. Only 1 patient had recurrence 6 months after surgery, which was managed by a second glans-preserving surgery without recurrence. With careful patient selection and vigilant follow-up, anatomically suitable superficial penile cancer can be offered this glans-preserving surgery, while preserving function of the penis wherever possible.
We report the first case of a healthy baby born after intrauterine insemination with vitrified swim-up spermatozoa from an oligoasthenozoospermic patient. A 39-year-old patient was subjected to intrauterine insemination...We report the first case of a healthy baby born after intrauterine insemination with vitrified swim-up spermatozoa from an oligoasthenozoospermic patient. A 39-year-old patient was subjected to intrauterine insemination with spermatozoa from her 35-year-old husband, diagnosed with oligoasthenozoospermia. The swim-up spermatozoa from 2 ejaculates were suspended in a culture medium supplemented with 1% human serum albumin and 0.25 M sucrose. Three hermetically packaged 100-μL sperm portions (each containing 1.0 × 10(6) spermatozoa/mL) were vitrified by direct plunging into liquid nitrogen. The presence of leukocytes in the ejaculates was determined by indirect immunofluorescence assay. Production of reactive oxygen species was measured by chemiluminescent assay. Before intrauterine insemination, all portions were warmed in culture medium at 37°C, and the spermatozoa were concentrated by centrifugation; they were then resuspended in 500 μL of culture medium and inseminated. The cell suspension used for insemination displayed 60% progressive motility. Clinical pregnancy was confirmed at 7 weeks of gestation, and a healthy baby was born at term. Our results show that a successful intrauterine insemination can be achieved with aseptic vitrification of spermatozoa.
Oral administration of testosterone has potential use for the treatment of hypogonadism. We have recently demonstrated that a novel formulation of oral testosterone transiently normalized serum testosterone in a single-d...Oral administration of testosterone has potential use for the treatment of hypogonadism. We have recently demonstrated that a novel formulation of oral testosterone transiently normalized serum testosterone in a single-dose pharmacokinetic study. In this report, we present the steady-state pharmacokinetics of this formulation. Twelve healthy young men were rendered hypogonadal with the gonadotropin-releasing hormone antagonist acyline (300 μg/kg subcutaneously) and administered 300 mg of oral testosterone 3 times daily for 9 days. Serum testosterone, dihydrotestosterone (DHT), estradiol, and sex hormone-binding globulin (SHBG) were measured before and 1, 2, 4, 5, 6, 8, 10, 11, 12, 14, 16, and 24 hours on the first and ninth day of dosing. Before testosterone administration, all men had serum testosterone under 75 ng/dL. Over day 1, the 24-hour average (geometric mean [%CV]) serum total testosterone was 378 (45) ng/dL. This decreased to 315 (41) ng/dL after 9 days of continuous treatment (P = .1 compared with day 1). The 24-hour average serum SHBG was 27 (46) nmol/L on day 1 and was significantly reduced to 19 (47) nmol/L by day 9 (P < .01). As a result, the calculated free testosterone values were similar between day 1 and day 9: 8.7 (43) and 8.3 (37) ng/dL, respectively. DHT was in the reference range and estradiol was slightly below on day 9. Oral testosterone (300 mg) dosed 3 times daily normalized serum testosterone in men with experimentally induced hypogonadism after 9 days of dosing and significantly suppressed SHBG. This formulation of oral testosterone may have efficacy for the treatment of testosterone deficiency.
Mammalian sperm surface antigens are acquired either during spermatogenesis or sperm maturation in the epididymis. These antigens, many of which are hydrolytic enzymes, are actively synthesized and secreted by the reside...Mammalian sperm surface antigens are acquired either during spermatogenesis or sperm maturation in the epididymis. These antigens, many of which are hydrolytic enzymes, are actively synthesized and secreted by the resident epithelial cells and adsorbed to the sperm membrane as part of posttesticular sperm modification. In this study, we aimed to investigate the expression of cathepsin-D (CAT-D) in human reproductive tissues and its distribution on the sperm surface in different sperm conditions. Immunohistochemical results revealed the expression of CAT-D in the somatic Sertoli and Leydig cells without showing any immunoreactivity in any germ cells, despite their engagement of the acrosomal system. A strong immunoreactivity of anti-CAT-D was also detected in the epididymal epithelium, chiefly in the principal cells, which are known to actively synthesize and secrete proteins into the epididymal lumen. The absence of CAT-D in the clear cells was unexpected because these cells are known to engage the endosomal machinery. We further showed that CAT-D was anchored on the sperm surface confined to the postacrosomal region without any lateral redistribution within the membrane during sperm capacitation. However, the enzyme underwent changes to be an active form of a 29/30-kd doublet during sperm capacitation. Using CAT-D as a marker, we were able to demonstrate here localization of the enzyme in human reproductive tissues, as well as reveal membrane modification in human sperm during maturation and capacitation processes.
The aim of this study was to evaluate the frequency of male accessory gland infection (MAGI) in patients with chronic bacterial prostatitis (CBP) plus irritable bowel syndrome (IBS) and to compare the sperm parameters of...The aim of this study was to evaluate the frequency of male accessory gland infection (MAGI) in patients with chronic bacterial prostatitis (CBP) plus irritable bowel syndrome (IBS) and to compare the sperm parameters of patients with or without MAGI. In addition, another objective of this study was to evaluate the ultrasound characterization of the anatomical space between the posterior wall of the prostate and the anterior wall of the rectum using transrectal ultrasonography. Fifty consecutive patients with the following criteria were enrolled: 1) infertility, 2) diagnosis of CBP, and 3) diagnosis of IBS according to the Rome III criteria. The following 2 age-matched control groups were also studied: infertile patients with CBP alone (n = 56) and fertile men (n = 30) who had fathered a child within the previous 3 months. Patients and controls underwent an accurate patient history; administration of the National Institutes of Health-Chronic Prostatitis Symptom Index and the Rome III questionnaires for prostatitis and IBS, respectively; physical examination; semen analysis; and transrectal ultrasound evaluation (limited to patients with CBP and IBS or CBP alone). A significantly higher frequency of MAGI was found in patients with CBP plus IBS (82.0%) compared with patients with CBP alone (53.6%) or fertile men (0%). The presence of MAGI in patients with CBP plus IBS was associated with a significantly lower sperm concentration, total number, and forward motility, and with a higher seminal leukocyte concentration compared with patients with CBP alone and MAGI. Sperm normal morphology was similar in the groups of patients. All sperm parameters did not differ significantly in both groups of patients without MAGI. With ultrasound evaluation, a significantly higher frequency of dilatation of prostatic venous plexus was found in patients with CBP plus IBS (75%) compared with patients with CBP alone (10%). Patients with CBP plus IBS had a significantly higher frequency of MAGI compared with patients with CBP alone. This was associated with worse sperm parameters and, hence, poorer reproductive prognosis. We suggest searching for the presence of IBS in patients with prostatitis syndrome, in particular when CBP and/or worse sperm parameters are present. Finally, this is the first observation on ultrasound examination of the anatomical space between the posterior wall of the prostate and the anterior wall of the rectum reported in patients with CBP and IBS. Further studies should clarify the meaning of the ultrasound findings.
We recently showed the diagnostic value of a new immunophenotype of blood endothelial progenitor cells (EPC) (CD45(-)/CD34(+)/CD144(+)) and endothelial microparticles (EMP) (CD45(-)/CD144(+)/annexin V(+)) in patients wit...We recently showed the diagnostic value of a new immunophenotype of blood endothelial progenitor cells (EPC) (CD45(-)/CD34(+)/CD144(+)) and endothelial microparticles (EMP) (CD45(-)/CD144(+)/annexin V(+)) in patients with arterial erectile dysfunction (AED), particularly in patients with associated late-onset hypogonadism and/or metabolic syndrome. In addition, we evaluated the effects of androgen replacement therapy, aerobic physical activity, and tadalafil administration on these markers. The aim of this study was to evaluate the serum concentrations of EPCs and EMPs in a large cohort of patients with AED according to severity of cavernous arterial insufficiency evaluated by penile Doppler. A total of 120 patients (aged 58.0 ± 6.0 years) with AED were enrolled in this study. Patients were classified into 3 groups based on value of peak systolic velocity (PSV). Group A: 37 patients with PSV <25 cm/s (severe arterial insufficiency); group B: 40 patients with PSV between 25 and 29 cm/s (moderate arterial insufficiency); group C: 43 patients with PSV between 30 and 34 cm/s (mild arterial insufficiency). Twenty patients (aged 60.0 ± 3.0 years) with psychogenic erectile dysfunction (PED) represented the control group. EPC and EMP blood concentrations were evaluated by flow cytometry. Patients with AED had significantly higher blood pressure, triglyceride levels, homeostasis model assessment index of insulin resistance, cavernous artery acceleration time, and intima-media thickness than those with PED, whereas International Index of Erectile Function score, high-density lipoprotein cholesterol level, and cavernous artery PSV were lower than those in PED. Both EPC and EMP levels were significantly higher in patients with AED compared with patients with PED. Among 3 groups of patients with AED, there were no significant differences in metabolic parameters examined, but group A showed significantly higher values of cavernous artery acceleration time and intima-media thickness than group B and group C. Finally, group A showed serum concentrations of EPCs and EMPs significantly higher compared with other groups with AED. Patients with AED showed worse metabolic parameters, cavernous artery parameters, and EPC and EMP levels compared with patients with PED. Among patients with AED, those with PSV <25 cm/s showed worse findings of endothelial dysfunction. This suggests that AED is an expression of endothelial damage and that this original immunophenotype of EPCs and EMPs may be considered a predictor of endothelial dysfunction in patients with AED. Finally, this study confirmed the reliability of penile Doppler evaluation integrated with these serum markers of endothelial dysfunction.
Microsurgical varicocelectomy has become the gold standard in adults because of low recurrence and postoperative hydrocele rates; it is increasingly applied in children and adolescents. This review aims to provide the su...Microsurgical varicocelectomy has become the gold standard in adults because of low recurrence and postoperative hydrocele rates; it is increasingly applied in children and adolescents. This review aims to provide the surgeon with the necessary surgical anatomy of the spermatic cord and with a step-by-step, anatomically justified description of technique, toward clearer comprehension and improved application. The anatomic compartments of the spermatic cord are delineated by the external and internal spermatic fasciae. Venous drainage of testis-epididymis is accomplished by the internal spermatic, deferential, and external spermatic (cremasteric) veins. All 3 anastomose at the caudal pole of testis, and then via gubernacular veins with the posterior scrotal veins. Another anastomosis exists between a cremasteric branch and anterior scrotal veins, which gives the external pudendal vein. Subinguinal approach offers access to varicose spermatic veins and collaterals. Use of surgical microscope offers identification of small veins, preservation of arteries, lymphatics, and nerves, and appreciation of spermatic cord fasciae, which permits the development of two surgical planes. In the surgical plane of internal spermatic vessels, internal spermatic veins are ligated, whereas the testicular artery and innervation, as well as lymphatics, are preserved. In the plane of cremasteric vessels and vas, cremasteric veins are ligated, whereas the cremasteric artery, vas deferens and its vasculature, lymphatics, and the genital branch of genitofemoral nerve are preserved. Delivery of the testis to ligate gubernacular veins is at the discretion of the surgeon. Finally, venous return is effected by deferential and scrotal veins, or, when gubernacular veins are ligated, by deferential veins only.
Some methods for determining sperm DNA fragmentation, such as the sperm chromatin structure assay (SCSA) and the sperm chromatin dispersion test (SCD), provide additional information about particular subgroups of spermat...Some methods for determining sperm DNA fragmentation, such as the sperm chromatin structure assay (SCSA) and the sperm chromatin dispersion test (SCD), provide additional information about particular subgroups of spermatozoa with specific irregularities. Thus, SCSA recognizes a specific sperm subpopulation, the high-DNA stainability sperm subpopulation (HDS), and SCD recognizes the so-called DNA-degraded sperm (DDS) subpopulation. Although some studies associate the presence of these subpopulations with specific aspects related to infertility, the relationship between both sperm subpopulations and their preponderance in specific clinical groups of infertile males has not been extensively investigated. In this study, HDS and DDS subpopulations were determined in a total of 37 human males: 8 males with proven fertility, 9 infertile males with asthenoteratozoospermia, 10 carriers of chromosomal reorganizations, and 10 infertile males with clinical varicocele. Results showed a significant increase of the DDS subpopulation (P < .001) in both the varicocele patient (16.85 ± 7.24) and carrier of rearranged genome (11.6 ± 5.23) groups, but not in patients with asthenoteratozoospermia (3.88 ± 1.55) or fertile donors (2.62 ± 1.68). No statistical differences were detected for the HDS subpopulation (P = .542), but the highest values were found in the varicocele and rearranged-genome groups. However, no correlation between the HDS and DDS subpopulations were found (r = 0.196; P = .244), suggesting that both represent a different class of sperm subpopulation in the ejaculate. A significant increase in HDS, and especially DDS, can be associated with the presence of varicocele or the rearrangement of chromosomes. Specific diagnostic tests to confirm the diagnosis must be performed in patients with increased DDS and HDS values.
One-third of infertile couples may have a male factor present. Illicit drug use can be an important cause of male factor infertility and includes use of anabolic-androgenic steroids, marijuana, opioid narcotics, cocaine,...One-third of infertile couples may have a male factor present. Illicit drug use can be an important cause of male factor infertility and includes use of anabolic-androgenic steroids, marijuana, opioid narcotics, cocaine, and methamphetamines. The use of these illicit drugs is common in the United States, with a yearly prevalence rate for any drug consistently higher in males compared with females. We aim to provide a review of recent literature on the prevalence and effects of illicit drug use on male fertility and to aid health professionals when counseling infertile men whose social history suggests illicit drug use. Anabolic-androgenic steroids, marijuana, cocaine, methamphetamines, and opioid narcotics all negatively impact male fertility, and adverse effects have been reported on the hypothalamic-pituitary-testicular axis, sperm function, and testicular structure. The use of illicit drugs is prevalent in our society and likely adversely impacting the fertility of men who abuse drugs.
Testicular torsion is a surgical emergency in urologic practice. Many models have demonstrated the relationship between the degree and duration of the torsion and the subsequent damages of the testis, but there are as ye...Testicular torsion is a surgical emergency in urologic practice. Many models have demonstrated the relationship between the degree and duration of the torsion and the subsequent damages of the testis, but there are as yet no suitable methods for visualization of the testicular microcirculation in this condition. We aimed to use orthogonal polarization spectral (OPS) imaging to observe the microcirculatory changes in the testis after ischemia-reperfusion (I/R) challenge, and to compare this technique with that of fluorescence intravital video microscopy (IVM). Twelve rats subjected to 60-minute ischemia following 720° testicular torsion were divided into two groups for IVM or OPS imaging examinations of the microcirculatory network of the testis at 60, 120, 180, and 240 minutes after reestablishment of perfusion. Significant microcirculatory failure was demonstrated after I/R in both groups. The absolute values of the microcirculatory parameters recorded with the OPS and IVM imaging methods did not differ statistically. The microcirculatory disturbances are present during the later phases of testicular torsion. OPS imaging technique represents an accurate noninvasive method to detect physiologic and pathophysiologic changes in the microcirculation of the testis.
The use of mobile phones is now widespread. A great debate exists about the possible damage that the radiofrequency electromagnetic radiation (RF-EMR) emitted by mobile phones exerts on different organs and apparatuses....The use of mobile phones is now widespread. A great debate exists about the possible damage that the radiofrequency electromagnetic radiation (RF-EMR) emitted by mobile phones exerts on different organs and apparatuses. The aim of this article was to review the existing literature exploring the effects of RF-EMR on the male reproductive function in experimental animals and humans. Studies have been conducted in rats, mice, and rabbits using a similar design based upon mobile phone RF exposure for variable lengths of time. Together, the results of these studies have shown that RF-EMR decreases sperm count and motility and increases oxidative stress. In humans, 2 different experimental approaches have been followed: one has explored the effects of RF-EMR directly on spermatozoa and the other has evaluated the sperm parameters in men using or not using mobile phones. The results showed that human spermatozoa exposed to RF-EMR have decreased motility, morphometric abnormalities, and increased oxidative stress, whereas men using mobile phones have decreased sperm concentration, decreased motility (particularly rapid progressive motility), normal morphology, and decreased viability. These abnormalities seem to be directly related to the duration of mobile phone use.
Endocrine regulation of the mouse initial segment (IS) and distal caput epididymides was studied using genome-wide profiling of gene expression. Among the IS-enriched genes, 29% were significantly down-regulated 1 day af...Endocrine regulation of the mouse initial segment (IS) and distal caput epididymides was studied using genome-wide profiling of gene expression. Among the IS-enriched genes, 29% were significantly down-regulated 1 day after gonadectomy. Of those genes, dihydrotestosterone (DHT) supplementation was not sufficient to maintain their pregonadectomy level of expression in 70%. Of the caput-enriched genes, 16% were significantly down-regulated after gonadectomy, and of those genes, DHT supplementation did not maintain the initial level of expression in 28%. Identical data were obtained by clustering analyses performed for the expression data of epididymal genes. Furthermore, the microarray data revealed that 26 androgen receptor coregulators were expressed in the epididymis, of which several were confirmed by quantitative reverse transcriptase polymerase chain reaction analysis. This suggests putative involvement of these proteins in the segment-specific regulation of the epididymal genes. The pattern of epididymal gene expression in the novel proximal epididymis-specific androgen receptor knockout mouse ProxE-ARKO, with severe hypotrophy and hypoplasia of the caput epithelium, furthermore suggested that a subset of genes whose expression cannot be maintained by systemic androgen alone still require either direct lumicrine androgen action or a permissive effect of circulating testosterone. It is evident that testicular factors, one of which could be the high-concentration luminal androgen, are important for the expression of IS-enriched genes, whereas the expression of distal caput-enriched genes is typically regulated by systemic androgens.
Cystatin-related epididymal spermatogenic (CRES) is the defining member of a reproductive subgroup within the family 2 cystatins of the cystatin superfamily of cysteine protease inhibitors. CRES is synthesized and secret...Cystatin-related epididymal spermatogenic (CRES) is the defining member of a reproductive subgroup within the family 2 cystatins of the cystatin superfamily of cysteine protease inhibitors. CRES is synthesized and secreted by the initial segment of the epididymis and is present in the sperm acrosome, suggesting roles in sperm maturation and fertilization. We have previously demonstrated that CRES is present within the epididymal lumen as monomeric (14 and N-glycosylated 19-kd forms) as well as sodium dodecyl sulfate-sensitive and sodium dodecyl sulfate-resistant high-molecular mass complexes. We have also shown that recombinant CRES protein will self-aggregate and form amyloid structures in vitro, raising the possibility that CRES might also form amyloid in vivo. Amyloid is a large protein aggregate with a specific cross-β sheet structure, and its presence is usually associated with disease. This review discusses protein aggregation in the epididymis and provides a brief overview of amyloid formation, including recent studies in other organ systems identifying examples of amyloid that are nonpathologic and carry out biologic functions (ie, functional amyloid). Studies that were carried out to determine if amyloid is present in the epididymal lumen and if CRES is associated with these structures are also described. The presence of CRES amyloid in the mouse epididymal lumen and the absence of pathology suggest either the presence of mechanisms to neutralize the cytotoxicity associated with pathologic amyloid or that CRES is a new example of a functional amyloid with roles in epididymal function.
The ability of spermatogenic cells to evade the host immune system and the ability of systemic inflammation to inhibit male reproductive function represent two of the most intriguing conundrums of male reproduction. Clea...The ability of spermatogenic cells to evade the host immune system and the ability of systemic inflammation to inhibit male reproductive function represent two of the most intriguing conundrums of male reproduction. Clearly, an understanding of the underlying immunology of the male reproductive tract is crucial to resolving these superficially incompatible observations. One important consideration must be the very different immunological environments of the testis, where sperm develop, and the epididymis, where sperm mature and are stored. Compared with the elaborate blood-testis barrier, the tight junctions of the epididymis are much less effective. Unlike the seminiferous epithelium, immune cells are commonly observed within the epithelium, and can even be found within the lumen, of the epididymis. Crucially, there is little evidence for extended allograft survival (immune privilege) in the epididymis, as it exists in the testis, and the epididymis is much more susceptible to loss of immune tolerance. Moreover, the incidence of epididymitis is considerably greater than that of orchitis in humans, and susceptibility to sperm antibody formation after damage to the epididymis or vas deferens increases with increasing distance of the damage from the testis. Although we still know relatively little about testicular immunity, we know less about the interactions between the epididymis and the immune system. Given that the epididymis appears to be more susceptible to inflammation and immune reactions than the testis, and thereby represents the weaker link in protecting developing sperm from the immune system, it is probably time this imbalance in knowledge was addressed.
Identification, detection, and use of small-ribonucleic acid (RNA) molecules have been paid increasing attention in the past decades. Here we show studies of two interrelated lines of this research in a sperm maturation-...Identification, detection, and use of small-ribonucleic acid (RNA) molecules have been paid increasing attention in the past decades. Here we show studies of two interrelated lines of this research in a sperm maturation-related organ, the epididymis. First, by using microarray and small-RNA library screening systems, a series of spatially and temporally regulated known and novel small regulatory RNA molecules, referred to as microRNAs, has been identified and characterized. Second, small double-stranded RNAs, called small interfering RNAs, emerged as a powerful tool to knock down gene expression by a pathway known as RNA interference. It has been successfully used to silence epididymal gene expression in vivo to elucidate the function of several sperm motility- and capacitation-related proteins in the rat epididymis.
Once shed from their fostering Sertoli cells, spermatozoa leave the testis and are transported passively by seminiferous fluid through the rete testis. Then, these immature cells enter the complex efferent duct system th...Once shed from their fostering Sertoli cells, spermatozoa leave the testis and are transported passively by seminiferous fluid through the rete testis. Then, these immature cells enter the complex efferent duct system that is joined to the unique and convoluted epididymal duct. This epididymal duct, lined by a continuous layer of epithelial cells joined by tight junctions, is a tube several meters long (up to 60 m in domestic mammals) and forms an organ that is classically subdivided into 3 major anatomical regions: the head/caput, the corpus/body, and the tail/cauda. Spermatozoa travel throughout the duct for several days to weeks, depending on the species, and may be stored for even longer periods in the cauda part of the epididymis and vas deferens. During their journey the proportion of potentially "mature" spermatozoa increases, but it is only when they reach the cauda epididymidis that almost all spermatozoa have acquired their natural fertilizing ability, which involves progressive motility, the ability to undergo the postejaculatory events (capacitation and hyperactivation), and the capacity to recognize and to bind to the oocyte investments and egg plasma membrane. Recent secretomic, proteomic, and transcriptomic studies have provided new information on the functions and the regionalization of the epididymis and revealed some insights into the complexity of epididymal fluid. Among genes and proteins highly expressed by this tissue, many have roles related to sperm protection (such as oxidation), but a large number of new compounds related to innate immunity have also been discovered. This review will focus on possible new control mechanisms that these studies have suggested for this tissue.
Sibutramine is a drug globally used for the treatment of obesity. The aim of this study was to investigate male reproductive disorders caused by sibutramine in adult rats. Wistar rats were treated for 28 consecutive days...Sibutramine is a drug globally used for the treatment of obesity. The aim of this study was to investigate male reproductive disorders caused by sibutramine in adult rats. Wistar rats were treated for 28 consecutive days (gavage) with 10 mg/kg of sibutramine. Control animals received only vehicle (dimethylsulfoxide and saline). The rats were sacrificed for evaluation of body and reproductive organ weights, sperm parameters, hormone levels (luteinizing hormone, follicle-stimulating hormone, and testosterone), testicular and epididymal histopathology, sexual behavior, fertility and in vitro contractility of the epididymal duct. Sibutramine decreased (P < .05) weights of the epididymis and ventral prostate, but not of other reproductive organs. The sperm number and transit time in the epididymal cauda were decreased (P < .001), but the daily sperm production was not altered. Moreover, morphology and sperm motility, histopathology of the testes and epididymis, sexual behavior, fertility, and serum hormone levels were not altered by the treatment. Sibutramine increased the potency of norepinephrine and, per se, increased the mechanical activity of the epididymal duct in vitro. Thus, although sibutramine in these experimental conditions did not interfere with the reproductive process of rats, it provoked acceleration of the sperm transit time and a decrease in the sperm reserves in the epididymal cauda. This alteration is probably related to the sympathomimetic effect of this drug, as shown by the in vitro assays. In humans, use of this drug might present a threat for male fertility because sperm reserves in men are naturally lower than those in rats.