Laura Moltoni

Evaluation of enzymatic and non-enzymatic antioxidants in seminal plasma of men with genitourinary infections, varicocele and idiopathic infertility.

This study was aimed to assess the antioxidant enzymatic and non‐enzymatic compounds in semen of infertile men. Seventy‐four infertile patients were grouped according to their clinical diagnosis: genitourinary infection, varicocele, idiopathic infertility. Semen samples of fertile men represent the control. Semen characteristics were evaluated by light and transmission electron microscopy (TEM). TEM data was quantified with a mathematical formula, which provides numerical scores. Spectrophotometric and HPLC methods were used to measure the amount of reduced (GSH), oxidised glutathione (GSSG), ascorbic acid (AA) and malondialdehyde (MDA, marker of lipid peroxidation) and the activity of glutathione reductase, catalase (CAT), glutathione peroxidase. Infertile groups showed significantly decreased values of sperm parameters vs. controls. In infection and varicocele groups, the seminal MDA levels were significantly increased when compared to controls (p < 0.001), indicating an alteration of oxidative status and a peroxidative damage. In infection and varicocele groups, AA levels were reduced (p < 0.05) vs. control; in the varicocele group, the GSH levels were also decreased (p < 0.05). Significantly higher CAT activity was observed in infection and varicocele groups vs. fertile men (p < 0.001 and p < 0.05 respectively). The GSH/GSSG ratio was significantly decreased in varicocele and idiopathic infertility groups vs. control (p < 0.01). The study of the alteration of a single parameter of oxidative stress or of the antioxidant system may not have a relevant clinical value to estimate male fertilising potential and the background of infertility causes, since complex and multifactorial mechanisms are involved in different pathologies. In our study, each pathology is characterised by a definite pattern of markers such as MDA and enzymatic and non‐enzymatic antioxidant compounds. In the different pathologies related to infertility, the identification of the complex of involved parameters could be useful in the diagnosis, prognosis and in the choice of a possible treatment such as specific antioxidant supplements.

Semen characteristics and malondialdehyde levels in men with different reproductive problems

The aim of this study was to assess the level of malondialdehyde (MDA) in the seminal plasma of infertile men and to highlight a relationship between the level of MDA and semen parameters. Eighty‐one infertile patients were divided into groups according to their clinical diagnosis: genitourinary infections, varicocele and idiopathic infertility. Semen quality was assessed by light and transmission electron microscopy (TEM). TEM data were quantified with a mathematical formula able to obtain a fertility index and the percentage of sperm apoptosis, immaturity, and necrosis. Seminal MDA levels were determined by spectrofluorometry. Scrotal Eco‐color Doppler was used to detect the varicocele. Infected patients had a positive bacteriological semen analysis. A control group consisted of 14 normospermic fertile men. Fertile group showed significantly increased values of sperm concentration, motility, and fertility index compared to infertile groups. In the infertile groups, sperm motility, concentration, apoptosis, and fertility index were not significantly different. In infection group, the percentage of necrosis was significantly higher than that observed in fertile men, varicocele, and idiopathic infertility groups (p < 0.001). MDA levels increased significantly in infection group in comparison with varicocele group (p < 0.01), idiopathic infertility group, and fertile men (p < 0.001) and in varicocele group compared to idiopathic infertility group (p < 0.001). In infection group, MDA levels positively correlated with sperm concentration (p < 0.01), fertility index (p < 0.05), and necrosis (p < 0.001), whereas a negative correlation was found with motility (p < 0.01). In varicocele group MDA levels correlated positively with necrosis and negatively with immaturity (p < 0.05). In fertile men and idiopathic infertility group, they did not show any correlation. In conclusion, we suggest that the evaluation of seminal MDA may be a good marker for understanding pathologies responsible of a sperm motility reduction such as urogenital infections or inflammatory status.

Adverse health effects from combustion-derived nanoparticles: the relative role of intrinsic particle toxicity and host response.

It is widely accepted that airborne pollution causes adverse health effects in humans (Gauderman et al. 2007). In addition to the concentration of particulate matter (PM), these effects have been related to innate particle toxicity. Stoeger et al. (2009) recently showed that, with a slope that significantly depends on particle structure, surface, and organic carbon content, combustion-derived nanoparticles behave in a different manner in in vitro systems and when reacting with lung surface (i.e. after particle–lung interaction). We have stressed that mechanistic linkages between PM and health effects should be investigated in more detail (Cetta et al. 2007, 2008). Here, we would like to comment on the role of the individual response in the occurrence of the clinically evident outcome, that is, how individual charac teris tics of the host, in the presence of the same (or similar) noxious agents, are responsible for or determine the type and the severity of the response. Until now, toxicity has been considered mainly as an intrinsic property of each pollutant, depending on size, type, and composition of each particle. Stoeger et al. (2009) focused specifically on structure, BET (Brunauer, Emmett, and Teller) surface area, and oxidative potency. Interestingly, they stressed particle–lung interaction and the ability of some particles rich in organic content, namely, soot with high organic content, to determine a higher than expected inflammatory response due to increased cytochrome P450 1A1 induction; they also introduced a new parameter, inflammatory efficacy, in addition to oxidative potency. In our opinion, this could be just the top of the iceberg. In fact, “oxidative stress” is a working hypothesis in the search for a common mechanistic linkage between particulate material and adverse health effects. But it is not unique. In particular, in a recent in vitro study in which different types of particles were used (PM < 2.5 or = 10 μm in aero dynamic diameter, tire debris), the same concentration of different particles with the same exposure time elicited different effects on sperm cell function (motility, viability, rate of apop-tosis) (Collodel G, Geminiani M, Cetta F, Camatini M, Bolzacchini E, Renieri T, unpublished data). However, variability of the observed effects was less than that elicited by changing the host, with lower adverse effects in New Zealand rabbit sperm, more evident effects in human sperm, and very severe effects in humans with previous impaired sperm function (e.g., varicocele). Sperm cell function is easy to quantify and compare not only among different pollutants but also among different host species or subgroups. These findings are in accordance with recent epidemiologic data showing more pronounced respiratory and cardiovascular effects in patients with previous respiratory and cardiovascular impairment or specific susceptibility, respectively (Gauderman et al. 2007). The results of these studies will also have relevant implications for policy makers (Cetta et al. 2007). In fact, until now, contrast measures have mainly been directed to reduce PM concentration. Curent evidence suggests that—more important than reducing the overall PM concentration—it is of paramount importance to reduce selectively the concentration of those pollutants that are more toxic or more strictly related with adverse health effects, such as traffic-related particles. In the future, because of the better knowledge of the host response and of the variability of individual susceptibility in the occurrence of these effects, a major goal for policy makers will be the proper and early recognition—by means of sensible and specific tests—of at-risk subpopulations. This early recognition of at-risk subpopulations could facilitate better prevention or reduction of negative effects of host–pollutant interactions.