Rosita A. Condorelli

Diabetes mellitus and sperm parameters.

Because of the paucity of studies and inconsistencies regarding the impact of diabetes mellitus (DM) on semen quality, this disease is seldom looked for in the infertile patient. Recently, this view has been challenged by findings showing that DM induces subtle molecular changes that are important for sperm quality and function. This brief review shows the main sperm parameters in patients with DM and presents the mechanisms hypothesized to explain the changes observed in these patients. The data available suggest that DM alters conventional sperm parameters. In addition, DM causes histologic damage of the epididymis, with a negative impact on sperm transit. Various mechanisms may explain the sperm damage observed in patients with DM. These include endocrine disorders, neuropathy, and increased oxidative stress. Many authors suggest that DM decreases serum testosterone levels. This is associated with a steroidogenetic defect in Leydig cells. In addition, diabetic neuropathy seems to cause atonia of seminal vesicles, bladder, and urethra. Furthermore, DM is associated with an increased oxidative stress, which damages sperm nuclear and mitochondrial DNA. Finally, spermatogenesis derangement and germ cell apoptosis in type 1 DM may relate to a local autoimmune damage, whereas insulin resistance, obesity, and other related comorbidities may impair sperm parameters and decrease testosterone serum levels in patients with type 2 DM.

Effects of the Exposure to Mobile Phones on Male Reproduction: A Review of the Literature

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.

Does alcohol have any effect on male reproductive function? A review of literature

Although alcohol is widely used, its impact on the male reproductive function is still controversial. Over the years, many studies have investigated the effects of alcohol consumption on sperm parameters and male infertility. This article reviews the main preclinical and clinical evidences. Studies conducted on the experimental animal have shown that a diet enriched with ethanol causes sperm parameter abnormalities, a number of alterations involving the reproductive tract inhibition, and reduced mouse oocyte in vitro fertilization rate. These effects were partly reversible upon discontinuation of alcohol consumption. Most of the studies evaluating the effects of alcohol in men have shown a negative impact on the sperm parameters. This has been reported to be associated with hypotestosteronemia and low-normal or elevated gonadotropin levels suggesting a combined central and testicular detrimental effect of alcohol. Nevertheless, alcohol consumption does not seem to have much effect on fertility either in in vitro fertilization programs or population-based studies. Finally, the genetic background and other concomitant, alcohol consumption-related conditions influence the degree of the testicular damage. In conclusion, alcohol consumption is associated with a deterioration of sperm parameters which may be partially reversible upon alcohol consumption discontinuation.

Effects of varicocelectomy on sperm DNA fragmentation, mitochondrial function, chromatin condensation, and apoptosis.

The aim of this study was to evaluate conventional semen parameters (density, morphology, and progressive motility) and the flow-cytometric parameters of DNA fragmentation, mitochondrial membrane potential, phosphatidylserine externalization, and chromatin compactness in patients with varicocele before and after varicocelectomy. Thirty men (26.5 ± 3.2 years old, range 20-32 years) with oligoasthenoteratozoospermia and grade 3 left varicocele were selected (without other causes of male infertility). Each of them underwent sperm analysis and flow cytometric evaluation before and 4 months after subinguinal microsurgical varicocelectomy (SMV). After varicocelectomy, men had significantly higher sperm density, progressive motility, and normal forms compared with baseline. They also had a significantly lower percentage of spermatozoa with low mitochondrial membrane potential. After SMV, they showed a significantly lower percentage of spermatozoa with phosphatidylserine externalization, an early sign of apoptosis. Significantly decreased percentages of spermatozoa with abnormal chromatin compactness and spermatozoa with DNA fragmentation were found after SMV compared with baseline. Subinguinal microsurgical varicocelectomy improves sperm function in oligoasthenoteratozoospermia secondary to grade 3 left varicocele. Improvements are seen in conventional parameters and biofunctional parameters not routinely evaluated.

Negative effect of increased body weight on sperm conventional and nonconventional flow cytometric sperm parameters.

Although with some discrepancy, obese men have been reported to have the worst conventional sperm parameters, but little is known about the effects of body weight on sperm mitochondrial function, chromatin condensation and apoptosis. This study was undertaken to evaluate conventional and nonconventional sperm parameters in nonsmoking overweight or obese men without any other cause known to alter sperm parameters. Fifty overweight, 50 obese, and 50 normal-weight healthy nonsmoking men were carefully selected. Each man underwent up to 2 sperm analyses and evaluation of mitochondrial membrane potential (MMP), phosphatidylserine (PS) externalization, chromatin compactness, and DNA fragmentation by flow cytometry. Overweight and obese men had significantly lower sperm progressive motility and normal forms than controls. They also had a significantly higher percentage of spermatozoa with low MMP. Obese, but not overweight, men showed a significantly higher percentage of spermatozoa with PS externalization, an early sign of apoptosis, and a lower percentage of viable spermatozoa. A significant increased percentage of spermatozoa with abnormal chromatin compactness was found in both overweight and obese men, whereas only obese men had a significantly higher number of spermatozoa with DNA fragmentation compared with controls. Healthy nonsmoking overweight and obese men have worse conventional and nonconventional sperm parameters than normal-weight controls. The important role played by these parameters in a couples fertility suggests a program of body weight loss among the therapeutic repertoire for male infertility.

Myoinositol: Does It Improve Sperm Mitochondrial Function and Sperm Motility?

OBJECTIVE To evaluate whether an improvement in mitochondrial membrane potential was associated with sperm motility amelioration and greater sperm recovery after the swim-up procedure. A second purpose was to evaluate the effects of myoinositol (MYO) on sperm apoptosis, quality of chromatin compaction, and DNA integrity. METHODS Spermatozoa from 20 normozoospermic men and 20 patients with oligo-astheno-teratozoospermia were incubated in vitro with 2 mg/mL of MYO or phosphate-buffered saline as a control for 2 hours. After this incubation period, sperm motility was evaluated. Flow cytometry was used to analyze the mitochondrial membrane potential, phosphatidylserine externalization, chromatin compactness, and DNA fragmentation. We also evaluated the total number of motile spermatozoa recovered after swim-up after incubation with MYO or phosphate-buffered saline. RESULTS MYO significantly increased the percentage of spermatozoa with progressive motility in both normozoospermic men and patients with oligo-astheno-teratozoospermia. Motility improvement in the latter group was associated with a significant increase in the percentage of spermatozoa with high mitochondrial membrane potential. MYO had no effects on mitochondrial function in spermatozoa from normozoospermic men. Sperm phosphatidylserine externalization, chromatin compactness, and DNA fragmentation were unaffected by MYO in both groups. After incubation with MYO, the total number of spermatozoa recovered after swim-up had improved significantly in both groups. CONCLUSION These data show that MYO increases sperm motility and the number of spermatozoa retrieved after swim-up in both normozoospermic men and patients with abnormal sperm parameters. In patients with oligo-astheno-teratozoospermia, the improvement in these parameters was associated with improved sperm mitochondrial function. These findings support the use of MYO in both in vivo- and in vitro-assisted reproductive techniques.

Circulating Endothelial Progenitor Cells and Endothelial Microparticles in Patients With Arterial Erectile Dysfunction and Metabolic Syndrome

Blood endothelial progenitor cells (EPC) and microparticles (EMP) have been proposed as markers of endothelial dysfunction. The aim of this study was to evaluate both EPCs and EMPs in patients with arterial erectile dysfunction (ED) and metabolic syndrome (MetS). To accomplish this, 100 patients (ages 45-60 years) with ED and MetS (Adult Treatment Panel III [ATP III] 1999 criteria) and 17 healthy men (ages 44-57 years) were selected. EPC (CD45(neg)/CD34(pos)/CD144(pos)) and EMP (CD45(neg)/CD144(pos)/Annexin V(pos)) blood concentrations were evaluated by flow cytometry, before and after administration of tadalafil (20 mg) on demand for 3 months. Before treatment, EPCs and EMPs were significantly higher in patients compared with healthy men. EPCs increased significantly after tadalafil administration, whereas EMPs did not differ significantly. EPCs correlated positively or negatively with body mass index and with some cavernous artery indices, both before and after tadalafil administration. EMPs showed only positive correlations with body mass index and some cavernous artery indices, both before and after tadalafil administration. Patients with arterial ED and MetS have higher EPCs and EMPs compared with healthy men; hence, these cells may be regarded as markers of cavernous artery dysfunction. Tadalafil administration increased EPCs but not EMPs, suggesting that this compound may play a role in the endothelial repair response.

Insulin Resistance Is an Independent Predictor of Severe Lower Urinary Tract Symptoms and of Erectile Dysfunction: Results from a Cross-Sectional Study

INTRODUCTION Several studies have linked the association between lower urinary tract symptoms (LUTS), erectile dysfunction (ED), and the presence of insulin resistance (IR) due to an underlined metabolic syndrome (MetS). AIM This study aims to determine the relationship between IR, sexual function, and LUTS and to demonstrate the ability of IR in predicting ED and severe LUTS. METHODS Between January 2008 to January 2013, 544 consecutive patients with benign prostatic hyperplasia-related LUTS were enrolled. LUTS and sexual function of the patients were evaluated by the International Index of Erectile Function (IIEF) and the International Prostate Symptom Score (IPSS). MetS was defined by the International Diabetes Federation. IR was defined as a homeostasis model assessment (HOMA) index of 3 or greater. MAIN OUTCOME MEASURES Uni- and multivariate logistic regression analysis was performed to assess significant predictors of severe LUTS (IPSS ≥ 20) and ED (IIEF-Erectile Function [IIEF-EF] <26), including MetS component, prostate volume, prostate-specific antigen, total testosterone, and HOMA index. RESULTS IR patients resulted in higher values of IPSS (19.0 vs. 15.0; P<0.01), IPSS-storage (6.0 vs. 5.0; P<0.01), IPSS-voiding (12.0 vs. 9.0; P<0.01), total prostate volume (54.8 vs. 36.5; P<0.01), and lower values of IIEF-EF (17.0 vs. 20.0; P<0.01), IIEF-Intercourse Satisfaction (3.0 vs. 10.0; P<0.01), IIEF-Orgasmic Function (8.0 vs. 9.0; P<0.01), IIEF-Overall Satisfaction (6.0 vs. 8.0; P<0.01), and total testosterone (3.83 vs. 4.44; P<0.01). IR was demonstrated to be a strong predictor of ED (IIEF-EF <26) (odds ratio [OR] =6.20, P<0.01) after adjusting for confounding factors. Finally, IR was also an independent predictor of severe LUTS (IPSS ≥ 20) (OR=2.0, P<0.01) after adjusting for confounding factors. CONCLUSIONS IR patients are at high risk of having severe LUTS and contemporary sexual dysfunctions. We strongly suggest to prevent LUTS and ED by reducing insulin resistance.

Microbiological investigation in male infertility: a practical overview

The roles of inflammation and/or infection of the male accessory sex glands are very important for the potential effects that these conditions may have on male fertility. The clinical andrologist should be aware of the pathophysiological role of the main determinants of sperm damage when these conditions occur, in particular, seminal leukocytes, oxidative stress and cytokines. In addition, it is important to have a good knowledge of the methodologies to be used in clinical practice. This article summarizes the methods used to look for and to identify the micro-organisms responsible for male urogenital tract infections. These include sperm culture, urine culture, urethral swabbing, the Meares-Stamey test and balanopreputial swabbing. Finally, we discuss the role of human papilloma virus infection in male infertility.

Pleiotropic Actions of Peroxisome Proliferator-Activated Receptors (PPARs) in Dysregulated Metabolic Homeostasis, Inflammation and Cancer: Current Evidence and Future Perspectives

Background: Peroxisome proliferator-activated receptors (PPARs) have demonstrated a lot of important effects in the regulation of glucose and lipid metabolism and in the correct functioning of adipose tissue. Recently, many studies have evaluated a possible effect of PPARs on tumor cells. The purpose of this review is to describe the effects of PPARs, their action and their future prospective; Methods: Narrative review aimed to synthesize cutting-edge evidence retrieved from searches of computerized databases; Results: PPARs play a key role in metabolic diseases, which include several cardiovascular diseases, insulin resistance, type 2 diabetes, metabolic syndrome, impaired immunity and the increasing risk of cancer; in particular, PPARα and PPARβ/δ mainly enable energy combustion, while PPARγ contributes to energy storage by enhancing adipogenesis; Conclusion: PPAR agonists could represent interesting types of molecules that can treat not only metabolic diseases, but also inflammation and cancer. Additional research is needed for the identification of high-affinity, high-specificity agonists for the treatment of obesity, type 2 diabetes (T2DM) and other metabolic diseases. Further studies are needed also to elucidate the role of PPARs in cancer.