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Background: The environment plays a key role in male infertility, changing the incidence in various populations, and pesticides are one of the most studied hazards. The use of the latter has never decreased, jeopardizing the safety of workers and the general population., Objective: Our purpose was to summarize the results of studies discussing the association between pesticides and male fertility., Methods: A comprehensive literature search was performed through MEDLINE via PubMed, Scopus, and Web of Science. Only human studies were considered. Semen parameters and DNA integrity were considered to evaluate the effect of pesticides on men., Results: A total of 64 studies that investigated their impact in terms of semen parameters (51 studies) and chromatin and DNA integrity (25 studies) were included. The most frequently affected parameters were total sperm count, sperm motility, and sperm morphology, although a reduction in ejaculate volume and concentration occur in several cases. A tangible worsening of semen quality was associated with organochlorines and organophosphates. Furthermore, pesticide exposure, especially pyrethroids, was related to a higher DNA fragmentation index and chromosome aneuploidy in most articles., Conclusion: The epidemiological evidence supports the association between pesticides and male fertility for workers and the exposed population in terms of semen quality, DNA fragmentation, and chromosome aneuploidy., (© 2022 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Background: So far, male genital tract color-Doppler ultrasound (MGT-CDUS) was not standardized. Recently, the European Academy of Andrology (EAA) published the results of a multicenter study assessing the CDUS characteristics of healthy-fertile men (HFM) to obtain normative parameters., Objectives: To report the EAA US study (i) standard operating procedures (SOPs) for assessing MGT-CDUS, (ii) main MGT-CDUS normative parameters, and (iii) compare the EAA and previously published "normal" CDUS values., Methods: A cohort of 248 HFM (35.3 ± 5.9 years) was studied, evaluating MGT-CDUS before and after ejaculation following SOPs., Results: SOPs for MGT-CDUS assessment are summarized here. All subjects underwent scrotal CDUS and 188 men underwent transrectal ultrasound before and after ejaculation. The main CDUS reference ranges and characteristics of the HFM-MGT are reported here. The mean testicular volume was ∼17 mL. The lower limit for right and left testis was 12 and 11 mL, defining testicular hypotrophy. The upper limit for epididymal head, body, tail, and vas deferens was 11.5, 5, 6, and 4.5 mm, respectively. Testicular and epididymal arterial reference ranges are reported. The EAA varicocoele classification is reported. CDUS-varicocoele was detected in ∼37% of men. Prostate mean volume was ∼25 mL, while lower and upper limits were 15 and 35 mL, defining hypotrophy and enlargement, respectively. Prostate arterial reference ranges are reported. Prostate calcifications and inhomogeneity were frequent; midline prostatic cysts were rare and small. Ejaculatory duct abnormalities were absent. The upper limit for periprostatic venous plexus was 4.5 mm. Lower and upper limits of seminal vesicles (SV) anterior-posterior diameter were 6 and 16 mm, defining hypotrophy or dilation, respectively. Seminal vesicle volume and ejection fraction reference ranges are reported. SV-US abnormalities were rare. Deferential ampullas upper limit was 6 mm. A discussion on the EAA and previously published "normal" CDUS values is reported here., Conclusions: The EAA findings will help in reproductive and general male health management., (© 2022 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Metabolic syndrome (MetS) is a highly prevalent condition among adult males, affecting up to 41% of men in Europe. It is characterized by the association of obesity, hypertension, and atherogenic dyslipidemia, which lead to premature morbidity and mortality due to cardiovascular disease (CVD). Male infertility is another common condition which accounts for about 50% of cases of couple infertility worldwide. Interestingly, male infertility and MetS shares several risk factors (e.g., smoking, ageing, physical inactivity, and excessive alcohol consumption), leading to reactive oxygen species (ROS) production and increased oxidative stress (OS), and resulting in endothelial dysfunction and altered semen quality. Thus, the present narrative review aims to discuss the pathophysiological mechanisms which link male infertility and MetS and to investigate the latest available evidence on the reproductive consequences of MetS.

Background: Male infertility is a problem that affects 10-15% of men of reproductive age. In particular, gametogenesis is a complex process in which inflammation may play a central role through the secretion of cytokines and the expression of microRNAs. We assessed the potential role of proinflammatory cytokines (TNF-α, IL-6 and IL-1α) and microRNAs (miR-146a-5p, miR-34a-5p and miR-23a-3p) in the seminal plasma of infertile men compared to controls, evaluating their correlation with seminal and biochemical parameters., Methods and Results: Expression of cytokines and microRNAs was analyzed by ELISA and q-PCR. Our data shows that IL-1α was significantly increased in the azoospermic group compared to controls, TNF-α mRNA was more expressed in the oligozoospermic group than controls. There were no significant differences in miRNAs expression among the three groups. The correlations between sperm parameters and inflammatory markers were evaluated, however no significance was highlighted., Conclusions: The determination of each inflammatory marker separately in the seminal plasma of subfertile men, despite some significant differences, does not have a diagnostic value in male infertility even if an assay of selective pro-inflammatory cytokines and microRNAs in the semen may improve the diagnosis of male infertility., (© 2021. The Author(s).)

Background: The management of male idiopathic infertility is heterogeneous. Although meta-analyses reported the effectiveness on pregnancy rate, the real clinical impact of follicle-stimulating hormone (FSH) was not evaluated so far. In Italy, FSH is approved by the National Medicines Agency (AIFA) for idiopathic infertile patients with FSH < 8 IU/L, independently of semen parameters., Aim: Primary endpoint was to record the therapeutic approach to the male partner of infertile couples. Secondary aim was to assess changes of semen parameters during FSH treatment., Methods: A multicentre, prospective, observational, clinical practice survey was carried out, enrolling the male partner of infertile couples attending ten Italian participating centres. Inclusion criteria were as follows: couple infertility, age >18 years and FSH serum levels <8 IU/L. Thus, all men in which AIFA allowed the FSH prescription were enrolled. Primary endpoint was the number of infertile patients treated with FSH. Secondary outcomes were semen parameters. The treating physician decided whether to offer FSH therapy and whether to re-evaluate the male partner., Results: A total of 718 infertile couples were enrolled, and 241 patients were re-evaluated (median follow-up: 4.5 months). In 64.9% (466 patients), a treatment was prescribed. FSH was prescribed in 397 patients (85.2% of treated men). Sperm concentration (P = .002) and normal form percentage (P < .001) significantly improved during FSH administration. No correlation was found between these parameters and FSH duration (P = .545 and P = .627, respectively) or dosage (P = .455 and P = .533, respectively). Among patients treated with FSH, the incidence of oligozoospermia decreased from 73.0% to 56.0% (P < .001) and teratozoospermia from 43.6% to 27.7% (P < .001)., Discussion: This first nation-wide survey reveals a FSH prescription rate of 55% in patients qualifying for treatment according to AIFA. Although the study was not designed to highlight FSH efficacy in male infertility, a slight increase in semen parameters was demonstrated in about half of the treated men without adverse events., (© 2019 American Society of Andrology and European Academy of Andrology.)

Introduction: Spermatogenesis is a highly complex process involving several thousand genes, only a minority of which have been studied in infertile men. In a previous study, we identified a number of Copy Number Variants (CNVs) by high-resolution array-Comparative Genomic Hybridization (a-CGH) analysis of the X chromosome, including 16 patient-specific X chromosome-linked gains. Of these, five gains (DUP1A, DUP5, DUP20, DUP26 and DUP40) were selected for further analysis to evaluate their clinical significance., Materials and Methods: The copy number state of the five selected loci was analyzed by quantitative-PCR on a total of 276 idiopathic infertile patients and 327 controls in a conventional case-control setting (199 subjects belonged to the previous a-CGH study). For one interesting locus (intersecting DUP1A) additional 338 subjects were analyzed., Results and Discussion: All gains were confirmed as patient-specific and the difference in duplication load between patients and controls is significant (p = 1.65 × 10(-4)). Two of the CNVs are private variants, whereas 3 are found recurrently in patients and none of the controls. These CNVs include, or are in close proximity to, genes with testis-specific expression. DUP1A, mapping to the PAR1, is found at the highest frequency (1.4%) that was significantly different from controls (0%) (p = 0.047 after Bonferroni correction). Two mechanisms are proposed by which DUP1A may cause spermatogenic failure: i) by affecting the correct regulation of a gene with potential role in spermatogenesis; ii) by disturbing recombination between PAR1 regions during meiosis. This study allowed the identification of novel spermatogenesis candidate genes linked to the 5 CNVs and the discovery of the first recurrent, X-linked gain with potential clinical relevance.

Androgens and a normal androgen receptor (AR) are required for normal spermatogenesis. We investigated polyglutamine (CAG) and a polyglycine (GGC) tract in Italian men with defective spermatogenesis. We studied a group of 40 infertile men with spermatogenesis failure without Y-chromosome microdeletions compared with 60 normozoospermic ones. The distributions of both polymorphisms, within the normal range of Caucasian populations, were similar among infertile men and controls. Nonetheless, we observed that the frequency comparison of each CAG allele showed a statistical difference in the allele CAG 22; GGC 17 was the more predominant allele in infertile men than in controls. Moreover, to investigate the hypothesis that semen characteristics are perturbed by androgen receptor allele variants, we tried to detect a link between triplets and sperm motility in all subjects (cases plus controls). Subjects were subdivided into three groups, based on calculated allele frequencies. A significantly decreased motility, related to a longer CAG and GGC tracts, and marked differences between the groups exist for both polymorphisms. Our data highlight a probable relationship between the allele CAG 22/GGC 17 and a defective spermatogenesis in infertile men, suggesting that these polymorphisms might have an important effect on AR function., (© 2013 Blackwell Verlag GmbH.)

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.

Both the bioenergetic and the antioxidant role of CoQ(10) suggest a possible involvement in sperm biochemistry and male infertility. CoQ(10) can be quantified in seminal fluid, where its concentration correlates with sperm count and motility. It was found that distribution of CoQ(10) between sperm cells and seminal plasma was altered in varicocele patients, who also presented a higher level of oxidative stress and lower total antioxidant capacity. The effect of vericocelectomy on partially reversing these biochemical abnormalities is discussed. The redox status of coenzyme Q(10) in seminal fluid was also determined: an inverse correlation was found between ubiquinol/ubiquinone ratio and hydroperoxide levels and between this ratio and the percentage of abnormal sperm forms. After the first in vitro observations CoQ(10) was administered to infertile patients affected by idiopathic asthenozoospermia, originally in an open label study and then in three randomized placebo-controlled trials; doses were around 200-300 mg/day and treatment lasted 6 months. A significant increase in the concentration of CoQ(10) was found, both in seminal plasma and sperm cells. Treatment also led to a certain improvement in sperm motility. In one of the studies there was also a decrease in plasma levels of follicle stimulating horhone (FSH) and luteinizine horhone (LH). Administration of CoQ(10) may play a positive role in the treatment of asthenozoospermia, possibly related to not only to its function in the mitochondrial respiratory chain but also to its antioxidant properties. Further studies are needed in order to determine whether there is also an effect on fertility rate., (Copyright © 2011 International Union of Biochemistry and Molecular Biology, Inc.)

We had previously demonstrated that Coenzyme Q10 [(CoQ10) also commonly called ubiquinone] is present in well-measurable levels in human seminal fluid, where it probably exerts important metabolic and antioxidant functions; seminal CoQ10 concentrations show a direct correlation with seminal parameters (count and motility). Alterations of CoQ10 content were also shown in conditions associated with male infertility, such as asthenozoospermia and varicocele (VAR). The physiological role of this molecule was further clarified by inquiring into its variations in concentrations induced by different medical or surgical procedures used in male infertility treatment. We therefore evaluated CoQ10 concentration and distribution between seminal plasma and spermatozoa in VAR, before and after surgical treatment, and in infertile patients after recombinant human FSH therapy. The effect of CoQ10 on sperm motility and function had been addressed only through some in vitro experiments. In two distinct studies conducted by our group, 22 and 60 patients affected by idiopathic asthenozoospermia were enrolled, respectively. CoQ10 and its reduced form, ubiquinol, increased significantly both in seminal plasma and sperm cells after treatment, as well as spermatozoa motility. A weak linear dependence among the relative variations, at baseline and after treatment, of seminal plasma or intracellular CoQ10, ubiquinol levels and kinetic parameters was found in the treated group. Patients with lower baseline value of motility and CoQ10 levels had a statistically significant higher probability to be responders to the treatment. In conclusion, the exogenous administration of CoQ10 increases both ubiquinone and ubiquinol levels in semen and can be effective in improving sperm kinetic features in patients affected by idiopathic asthenozoospermia.

Objective: To evaluate the effectiveness of coenzyme Q(10) treatment in improving semen quality in men with idiopathic infertility., Design: Placebo-controlled, double-blind randomized trial., Setting: Andrology Unit, Department of Internal Medicine, Polytechnic University of Marche, Italy., Patient(s): Sixty infertile patients (27-39 years of age) with the following baseline sperm selection criteria: concentration >20 x 10(6)/mL, sperm forward motility <50%, and normal sperm morphology >30%; 55 patients completed the study., Intervention(s): Patients underwent double-blind therapy with coenzyme Q(10), 200 mg/day, or placebo; the study design was 1 month of run-in, 6 months of therapy or placebo, and 3 months of follow-up., Main Outcome Measure(s): Variations in semen parameters used for patient selection and variations of coenzyme Q(10) and ubiquinol concentrations in seminal plasma and spermatozoa., Result(s): Coenzyme Q(10) and ubiquinol increased significantly in both seminal plasma and sperm cells after treatment, as well as spermatozoa motility. A weak linear dependence among the relative variations, baseline and after treatment, of seminal plasma or intracellular coenzyme Q(10) and ubiquinol levels and kinetic parameters was found in the treated group. Patients with a lower baseline value of motility and levels of coenzyme Q(10) had a statistically significant higher probability to be responders to the treatment., Conclusion(s): The exogenous administration of coenzyme Q(10) increases the level of the same and ubiquinol in semen and is effective in improving sperm kinetic features in patients affected by idiopathic asthenozoospermia.

The role of partial AZFc deletions of the Y chromosome in spermatogenic impairment is currently debated. Recently, it was also reported that duplications of the same region are associated with oligozoospermia in Han-Chinese men. The aims of this study were (1) to evaluate the clinical significance of partial AZFc deletions in a large study population and (2) to define if partial AZFc duplications are a risk factor for spermatogenic failure also in a Caucasian population such as the Italian. We screened 556 infertile patients and 487 normozoospermic controls for partial AZFc deletions with a combined method based on STS+/- followed by CDY1-DAZ gene dosage and copy analysis. For the second aim, we performed CDY1-DAZ gene dosage in 229 infertile patients and 263 normozoospermic controls. The frequency of gr/gr deletions in patients was significantly different from the controls (3.2 vs. 0.4%, respectively; P < 0.001), with an OR = 7.9 (95% CI 1.8-33.8). b2/b3 deletions were rare in both groups (0.5% in patients, 0.2% in controls). Concerning gr/gr duplications, we observed no significant differences in their frequency between cases (2.6%) and controls (3.8%). This is the largest study population in the literature in which all potential methodological and selection biases were carefully avoided to detect the clinical significance of partial AZFc deletions and duplications. Our study provides strong evidence that gr/gr deletion is a risk factor for impaired spermatogenesis, whereas we did not detect a significant effect of b2/b3 deletions and partial AZFc duplications on spermatogenesis in this Caucasian ethnic group.

Objective: To detect peroxynitrite and 3-nitrotyrosine production in human spermatozoa of asthenozoospermic infertile patients and normospermic donors, and evaluate any influence on kinetic sperm features., Design: Basic study., Setting: Andrology Unit, Dept of Internal Medicine and Biochemistry Institute, Polytechnic University of Marche, Italy., Patient(s): Sixty-nine infertile patients affected by idiopathic asthenozoospermia and 29 normal fertile donors., Intervention(s): No therapeutic intervention was performed on patients., Main Outcome Measure(s): Production of peroxynitrite (ONOO-) and 3-nitrotyrosine by human spermatozoa; kinetic sperm cells parameters., Result(s): Normospermic fertile donors exhibited ONOO- concentrations significantly lower than those of asthenozoospermic infertile men (9.11 +/- 3.37 vs. 27.46 +/- 5.77 nmol/10(6) cells); confocal microscopy showed that ONOO- was more evident in spermatozoa of patients than in healthy donors. Moreover, a significant negative correlation was evident between ONOO- concentration and total sperm motility, curvilinear velocity (VCL), straight progressive velocity (VSL), and linearity coefficient. Finally, an increase was found in the nitration of the tyrosine residues in asthenozoospermic samples compared to controls., Conclusion(s): Spontaneous tyrosine nitration occurs in human spermatozoa. This post-translational protein modification is enhanced by an overproduction of peroxynitrite, which is more evident in asthenozoospermic infertile patients when compared with normospermic fertile donors. Motility parameters are negatively affected, suggesting that ONOO- may be involved in defective sperm function.

Background: Although the importance of estrogens in male reproduction is indisputable, little attention has been paid to the role of estrogen receptor (ER) gene mutations in male infertility. Significant correlation between (TA)n repeat allelic variants and lumbar bone mineral density was previously observed in the promoter region of the ERalpha gene, indicating that allelic combinations with higher number of (TA)n repeats are functionally more active genetic variants., Methods: We studied the (TA)n repeat polymorphism situated in the promoter region of the ERalpha gene in a large group of infertile and normospermic men (n = 347)., Results: Although the (TA)n polymorphism failed to show a significant association with male infertility, we found a significant effect of this polymorphism on sperm count. In the group of infertile men, the mean TA repeat number and sperm concentration (P = 0.022) and total sperm number (P = 0.043) were inversely correlated, showing an association between higher TA repeat number (genotype A) and lower sperm production. In line with this observation, normospermic subjects with genotype A had a significantly lower mean sperm concentration with respect to men bearing genotype B with shorter TA alleles (P < 0.05) and a lower total sperm count (P < 0.01)., Conclusions: Our data indicate that specific allelic combinations of the ERalpha, which confer a stronger estrogen effect, may negatively influence human spermatogenesis.

The goal of this study was to examine the effect of palmitoylethanolamide (PEA) on the capacitation process and hyperactivated motility (HA) in idiopathic infertile men. Our data show the effect of PEA on the kinematic parameters of sperm cells from idiopathic infertile men during the capacitation of spermatozoa in vitro, both in the presence and absence of 2.5 nM PEA, a molecule physiologically present in human reproductive tracts. Two groups of sperm cells were identified. In group I (36 +/- 14 x 10(6) cells/mL), PEA significantly increased some motility parameters and HA during capacitation. In group II (58 +/- 18 x 10(6) cells/mL), PEA did not significantly modify motility parameters and HA. Fura 2 AM (acetoxymethyl ester derivative of fura 2) measurements demonstrated that PEA increased external Ca2+ influx (which modulates HA) in group I, while no change was measured in group II. In conclusion, our data indicated that PEA modulated certain physiological sperm functions that are involved in fertilization; in particular, we showed that PEA modulated for HA in men with low sperm kinematic parameters.

This review is focused upon the role of coenzyme Q(10) in male infertility in the light of a broader issue of oxidative damage and antioxidant defence in sperm cells and seminal plasma. Reactive oxygen species play a key pathogenetic role in male infertility besides having a well-recognized physiological function. The deep involvement of coenzyme Q(10) in mitochondrial bioenergetics and its antioxidant properties are at the basis of its role in seminal fluid. Following the early studies addressing its presence in sperm cells and seminal plasma, the relative distribution of the quinone between these two compartments was studied in infertile men, with special attention to varicocele. The reduction state of CoQ(10) in seminal fluid was also investigated. After the first in vitro experiments CoQ(10) was administered to a group of idiopathic asthenozoospermic infertile patients. Seminal analysis showed a significant increase of CoQ(10) both in seminal plasma and in sperm cells, together with an improvement in sperm motility. The increased concentration of CoQ(10) in seminal plasma and sperm cells, the improvement of semen kinetic features after treatment, and the evidence of a direct correlation between CoQ(10) concentrations and sperm motility strongly support a cause/effect relationship. From a general point of view, a deeper knowledge of these molecular mechanisms could lead to a new insight into the so-called unexplained infertility.

Based on association studies, an increasing number of gene polymorphisms have been proposed as modulators of spermatogenesis. Interestingly, a clear cause-effect relationship between a polymorphism of the POLG gene and oligo(astheno)zoospermia was recently described. The POLG gene contains a polymorphic CAG repeat, and the presence of a homozygous mutant (not10/not10 CAG) genotype was found only in infertile men. In the present study, a large number of infertile patients and normospermic men of Italian origin were studied to define the effect of POLG genotypes on spermatogenic potential and whether the homozygous mutant is specific for spermatogenic disturbances. The mutated genotype was found at the same frequency in both infertile and normospermic men. Mean values of sperm parameters such as sperm count, motility, and morphology did not differ significantly between carriers of the three different genotypes. Our study failed to confirm any influence of the POLG gene polymorphism on the efficiency of the spermatogenesis. More importantly, considering that the homozygous mutant genotype has been found in normospermic fertile men, the analysis of the CAG repeat tract of the POLG gene does not appear to have any clinical diagnostic value.

Nitric oxide (NO) is a free radical generated from the oxidation of L-arginine to L-citrulline by 3 isoforms of reduced nicotinamide adenine dinucleotide phosphate (NADPH)-dependent NO synthases. Several data suggest a relevant role in sperm cell pathophysiology, but any conclusive data on its role in spermatozoa motility are still lacking. In the present study, we have correlated NO concentration in semen and kinetic features of sperm cells from normozoospermic fertile donors and infertile patients affected by idiopathic asthenozoospermia. Normozoospermic fertile men exhibited NO concentrations that were significantly lower than those of asthenozoospermic infertile men. A significant linear negative correlation was evident between NO concentration and percentage of total sperm motility. A further significant linear negative correlation was found between NO concentration and spermatozoa kinetic characteristics determined by a computerized analysis (curvilinear and straight progressive velocity). These data suggest that the overproduction of this free radical and the consequent excessive exposure to oxidative conditions have a potential pathogenetic implication in the reduction of sperm motility. The positive role played by NO in spermatozoa capacitation leads us to speculate that such paradoxical involvement in both pathologic and physiologic processes depends on the alternative redox state and relative level of NO.

Background: In spite of many years of debate, the impact of varicocele on male infertility is still controversial since its pathogenetic role on the impairment of semen quality has never been fully demonstrated., Methods: In the present work, a series of 426 young adult males undergoing percutaneous treatment of varicocele were studied and semen parameters were evaluated at baseline and 12 months of follow-up., Results: A significant increase in sperm cell concentration and a decrease in immotile spermatozoa were found after varicocele repair, but we failed to detect any significant positive change in progressive motility as well in sperm morphology after treatment. Similar results were also obtained when semen parameters were correlated with the degree of varicocele., Conclusion: Since a spontaneous improvement in semen quality has been mathematically established as a model of regression toward the mean, we conclude that the correction of varicocele in young adults is not a major indication when semen alteration is the only clinical problem., (Copyright 2004 S. Karger AG, Basel)

Previously we demonstrated that coenzyme Q10 (CoQ10) is present in human seminal fluid and shows a direct correlation with seminal parameters except in patients with varicocele (VAR). We have now evaluated CoQ10 distribution in VAR, versus control subjects, in order to discover metabolic abnormalities within this condition. We studied 32 patients with VAR (11 with oligoasthenozoospermia, 13 with asthenozoospermia, and 8 with normozoospermia), and, as controls, the following groups of subjects, matched with VAR patients according to seminal parameters: 16 patients with idiopathic oligozoospermia, 11 patients with isolated asthenozoospermia, and 14 normal fertile men. CoQ10 was assayed in total seminal fluid, plasma, or cell pellet by high-performance liquid chromatography (HPLC). We found a significantly higher proportion of CoQ10 in seminal plasma in VAR; cellular CoQ10 showed an inverse correlation with sperm concentration and motility in VAR, at variance with controls. As seminal plasma ubiquinone reflects an interchange between intracellular and extracellular compartments, the different distribution in VAR patients could represent a greater sensitivity to peroxidative damage and could suggest reduced utilization for energy, which in turn could cause a defective motility even in patients with a normal cell count. These data suggest a pathophysiological role of CoQ10 in seminal plasma and a possible molecular defect in VAR., (Copyright 2003 Elsevier, Inc. All rights reserved.)

Levels of coenzyme Q10 (CoQ10) and of its reduced and oxidized forms (ubiquinol, QH2, and ubiquinone, Qox) have been determined in sperm cells and seminal plasma of idiopathic (IDA) and varicocele-associated (VARA) asthenozoospermic patients and of controls. The results have shown significantly lower levels of coenzyme Q10 and of its reduced form, QH2, in semen samples from patients with asthenospermia; furthermore, the coenzyme Q10 content was mainly associated with spermatozoa. Interestingly, sperm cells from IDA patients exhibited significantly lower levels of CoQ10 and QH2 when compared to VARA ones. The QH2/Qox ratio was significantly lower in sperm cells from IDA patients and in seminal plasma from IDA and VARA patients when compared with the control group. The present data suggest that the QH2/Qox ratio may be an index of oxidative stress and its reduction, a risk factor for semen quality. Therefore, the present data could suggest that sperm cells, characterized by low motility and abnormal morphology, have low levels of coenzyme Q10. As a consequence, they could be less capable in dealing with oxidative stress which could lead to a reduced QH2/Qox ratio. Furthermore, the significantly lower levels of CoQ10 and QH2 levels in sperm cells from IDA patients, when compared to VARA ones, enable us to hypothesize a pathogenetic role of antioxidant impairment, at least as a cofactor, in idiopathic forms of asthenozoospermia.

Objective: To determine, by a simple fluorescence method, sperm plasma membrane alterations related with changes of lipid bilayer that, together with routine semen analysis, could help to elucidate the causes of the unexplained male infertility problems., Design: Pilot study., Setting: Andrology laboratory and biochemistry institute, medical school., Patient(s): Men whose semen was studied for infertility problems., Interventions(s): No therapeutic intervention was performed on patients., Main Outcome Measure(s): Presence of spermatozoa plasma membrane alterations evidenced by evaluation of Laurdan fluorescence Generalized Polarization (GP) and reported as a function of increasing cell concentration, spermatozoa total motility, linear speed, and vitality., Result(s): Reporting GP values as a function of increasing sperm cell concentration, it is evident that the samples are distributed in two distinct areas: at >32 x 10(6) cells per milliliter, mean GP value was 0.303 +/- 0.015, whereas for lower sperm cell concentrations, the mean GP was 0.365 +/- 0.026 (P<.001). These data indicate that the spermatozoa plasma membranes are characterized by liquid-crystalline phases with different ordering degree and polarity and that about 50% of samples with normal semen characteristics (> or =20 x 10(6) cells per milliliter) show high GP values., Conclusion(s): Laurdan fluorescence can be used as a simple method to evaluate spermatozoa plasma membrane alterations, particularly in a group of infertile men presenting normal semen parameters. In these samples, Laurdan could be used as a simple tool for infertility assessment. In fact, it is known that compositional and physicochemical alterations of bilayer features can be important for the fertilizing ability of spermatozoa because they are necessary for a proper physiological membrane activity.