Sperm forward motility is negatively affected by short-term exposure to altitude hypoxia.

Human exposure to altitude is a model to study the role of oxygen in different areas of physiology and pathophysiology. The aim of this study was to evaluate whether a short exposure to hypoxia (5 days) combined with exercise, at altitude ranging from 900 m above sea level to 5895 m above sea level (Kilimanjaro Expedition) can modify seminal and reproductive hormonal parameter levels in human beings. During the ascent, blood oxygen saturation at 3.848 m above sea level was found to be decreased when compared to sea level (P < 0.02). The sperm forward motility at sea level after the expedition showed a significant reduction ​​(P < 0.02). There were no changes in other seminal parameters among those compared. Determination of the hormonal plasma concentrations showed that baseline values of follicle-stimulating hormone, total testosterone, prolactin and oestradiol were unchanged at sea level after the hypoxic experience, with respect to baseline values at sea level. On the other hand, luteinising hormone levels after altitudes trekking significantly increased compared to levels before the expedition (P < 0.05). Because of the short-term exposure, we can assume that the reduced forward motility described here may result from the effects of the acute altitude hypoxia on spermatozoa during the epididymal transit where they mature acquiring their motility.

Serum from patients with erectile dysfunction inhibits circulating angiogenic cells from healthy men: relationship with cardiovascular risk, endothelial damage and circulating angiogenic modulators.

Erectile dysfunction (ED) is an early manifestation of arteriosclerosis associated with endothelial damage/dysfunction and to a blunted ability of cultured mononuclear circulating cells (MNCs) to differentiate circulating angiogenic cells (CACs), putatively involved in endothelial damage repair. Here we explored effects of human serum (HS) from patients with ED and cardiovascular risk factors (VRFs) but no clinical atherosclerosis, on cultured MNCs of healthy men to differentiate CACs and to form colonies. Effect of HS on number of CACS and of colony forming units (CFUs) was correlated with circulating markers of endothelial damage and with angiogenic modulators. MNCs from healthy men were cultured in standard conditions or with 20% HS from 35 patients with ED and from 10 healthy men. CACs were identified after 7 days of culture by uptake of acetylated low-density lipoprotein with concomitant binding of Ulex europaeus agglutinin I. CFUs were counted after 5 days of culture. Enzyme-linked immunosorbent assays assessed plasmatic soluble (s) form of E-selectin, Endothelin (ET)-1, tissue type plasminogen activator (tPA), vascular endothelial growth factor (VEGF)(165) and sVEGF receptor (R)-1. The number of CACs and of CFUs from healthy men was reduced after culturing MNCs with HS compared to standard medium. The inhibitory effect was significantly higher with HS from ED patients with higher or lower VRF exposure compared to healthy men. Inhibition was positively correlated with VRFs exposure, with ED severity, with common carotid artery intima media thickness measured using B-mode ultrasound, and to a lesser extent with plasmatic sE-Selectin, sET-1 and sVEGFR-1. Dysfunction of cells involved in vascular homoeostasis is induced by soluble factors still unknown and already present in a very initial systemic vascular disease in men with ED and VRFs.

Beta-chemokine receptor CCR5 in human spermatozoa and its relationship with seminal parameters.

BACKGROUND: Chemokine receptor CCR5, the main HIV-1 coreceptor, is present in the human spermatozoa. This study aimed to investigate (i) whether the percentage of CCR5-positive spermatozoa varies under conditions associated with changes in the membrane architecture, such as capacitation and fixation/permeabilization procedures; (ii) whether there is any relationship between individual variability in sperm CCR5 expression and semen parameters. METHODS AND RESULTS: In cytometric analysis, the percentage of CCR5-positive unfixed spermatozoa varied from approximately 10 to approximately 60%, and it significantly decreased after 5 h capacitation. The percentage of CCR5-positive spermatozoa was increased to more than 90% following fixation and permeabilization, suggesting the existence of large intracellular pools of the receptor. Immunocytochemistry showed positive staining in the anterior region of the sperm head. In ejaculates from male partner of 102 infertile couples, the CCR5 expression rate significantly correlated with sperm count, total sperm number and forward motility, but not with sperm morphology. In stepwise analysis, only forward motility entered into the model; however, this explained only approximately 8% of the variability in CCR5 expression. Interquartile analysis showed significant differences between the first and fourth quartiles of CCR5 expression for all semen parameters, except morphology. CONCLUSIONS: The percentage of CCR5-positive spermatozoa may vary under conditions associated with changes in membrane architecture and spermatozoa showed large intracellular pools of CCR5. A lower expression of CCR5 in asthenozoospermia seems to be suggested; however, it would only partially contribute to the inter-individual variability in the CCR5 expression. A genetic basis can be hypothesized to explain the variability.

RANTES and human sperm fertilizing ability: effect on acrosome reaction and sperm/oocyte fusion.

Beta-chemokine, regulated on activation and normally T-cell expressed and presumably secreted (RANTES), is present in both the male and female genital tract fluids where its levels increase in diseases related to infertility, such as endometriosis and male genital tract infections. beta-Chemokine receptors (CCR3 and CCR5) are expressed on freshly ejaculated human sperm cells and a sperm chemoattractant effect for RANTES has been reported. No information exists on other possible roles of RANTES on sperm functions involved in the fertilization process. In the present study, the exposure of sperm suspensions to high concentrations of the chemokine, comparable to those observed in inflammatory diseases, significantly decreased the stimulatory effect exerted by progesterone on sperm/oocyte fusion, evaluated by means of the hamster egg penetration test. Accordingly, a large proportion of spermatozoa preincubated under capacitating conditions with high concentrations of RANTES underwent a premature acrosome reaction (AR) that prevented subsequent progesterone-induced AR. Finally, sperm samples exposed to the same high levels of chemokine showed a significant increase in the intracellular levels of cAMP, which is involved in capacitation and AR dynamics. These results indicate a negative interference of high levels of RANTES on the sperm fertilizing ability, thereby suggesting a potential contribution of this chemokine to subfertility associated with endometriosis and genital tract inflammatory diseases.

Psychological features in men with erectile dysfunction with or without preclinical atherosclerosis.

Psychological distress was assessed with a multidimensional self-report questionnaire (Symptom Check-List-90R) in 247 men complaining of erectile dysfunction (ED), with or without preclinical atherosclerosis. This was estimated by ultrasound determination of intima-media thickness (IMT) in common carotid arteries (CC). Psychological distress was reported in 31% of men and was more prevalent in those with a vascular damage. A higher level of obsessive-compulsive (OC) features was observed in men with high CC-IMT (P=0.0069; OR 3.18, CL 1.31-7.80). Among a large number of vascular risk factors, elevated CC-IMT and a severe ED resulted independently associated with an elevated level of OC features (OR 3.36, CL 1.38-8.15; OR 2.60, CL 1.01-6.70, respectively). Mental stress driven by OC features may link ED and vascular disease by activating reciprocal exacerbating mechanisms. Psychological distress identifies men at risk for cardiovascular disease that deserve a vigorous treatment of ED to reduce risk of vascular events.

Vascular aetiology of erectile dysfunction.

Erectile dysfunction (ED) shares the same vascular risk factors (VRFs) with coronary arteries disease (CAD). A reduced biological activity of endothelium-derived nitric oxide links human atherosclerosis to ED and underscores the role of an altered endothelium in the pathogenesis of both conditions. ED is associated to a systemic endothelial cell activation/dysfunction independent from VRFs or from a diffuse vascular damage, indicating that ED is a marker of an early systemic endothelial damage, a relevant determinant of atherosclerosis. A diffuse vascular damage of carotid arteries indicative of pre-clinical atherosclerosis is significantly associated to an increased risk of severe ED in men with VRFs but without clinical atherosclerosis and ED was the most efficient predictor of angiographically verified silent CAD among different VRFs in uncomplicated type 2 diabetes. In conclusion, ED may be the only clinical correlate of a diffuse, unrecognized vascular damage that is associated to a documented future risk of acute vascular events. Searching ED might be of relevance in men with VRFs but no other clinical atherosclerosis to identify patients that should aggressively reduce their VRFs while treating ED.

Immunophenotypical characterization of contractile cells in caput epididymidis of men affected by congenital or post-inflammatory obstructive azoospermia.

Myoid cells of the human caput epididymidis are replaced by large cells with ultrastructural features of smooth muscle cells (SMC) in chronic obstruction of the male genital tract. To evaluate whether these cellular changes are associated with different functional phenotypes we analysed the immunohistochemical expression of myosin heavy chain isoforms and of extracellular matrix (EM) components in the human caput epididymidis contractile cells in normal and in obstructed epididymides. Normal caput epididymidis myoid cells expressed a scattered immunostaining for SM2, marker of differentiated contractile SMC, while no staining was detected for SMemb (the non-muscle-type myosin heavy chain isoform) and for its transcription factor BTEB2, markers of undifferentiated proliferating SMC. A faint immunoreaction (IR) for EM was observed in the peritubular wall of the normal caput. In the contractile wall of the obstructed caput epididymidis a strong IR was detected for all myosin heavy chain isoforms as well as for collagen type IV and for fibronectin, markers for a secretory function of SMC. These findings, unknown in other models of SMC pathophysiology, suggest that myoid cells resume the molecular machinery of both mature SMC and of differentiating/secretory cells in the chronic obstruction of the human caput. Contractile cells of the epididymal duct represent a unique model to study the plasticity of SMC.

Expression of gp20, a human sperm antigen of epididymal origin, is reduced in spermatozoa from subfertile men.

gp20, a sialylglycoprotein of human sperm homologous to CD52, is present everywhere on the surface of the freshly ejaculated sperm but is prevalently localized in the equatorial region of the head of capacitated sperm. In the present study, we confirmed this feature on large scale and correlated equatorial exposure of the antigen to the presence of serum albumin (SA) in the capacitation medium. Furthermore, we analyzed the relationship between the presence of the antigen and its equatorial exposure after capacitation and fertility, by comparing immunostaining for gp20 in the motile fraction of spermatozoa from fertile and subfertile men. A significantly higher percentage of nonimmunostained spermatozoa before capacitation (38.5% +/- 23 vs. 12% +/- 7, P < 0.0001) and a lower increase in the percentage of sperm with equatorial localization after capacitation (19.3% +/- 25 vs. 34.6% +/- 22, P = 0.039) were observed in subfertile men (n = 60) compared to fertile men (n = 15). In the whole study group, a positive correlation was also found between the percentage of spermatozoa exhibiting equatorial localization in capacitated samples and normal head forms (R = 0.50; P < 0.0001).