Gianni Forti

SUMO1 in human sperm: new targets, role in motility and morphology and relationship with DNA damage

In studies carried out previously, we demonstrated that small ubiquitin-like modifier 1 (SUMO1) is associated with poor sperm motility when evaluated with a protocol that reveals mostly SUMO1-ylated live sperm. Recently, with another protocol, it has been demonstrated that SUMO is expressed in most sperm and is related to poor morphology and motility, suggesting that sumoylation may have multiple roles depending on its localisation and targets. We show herein, by confocal microscopy and co-immunoprecipitation, that dynamin-related protein 1 (DRP1), Ran GTPase-activating protein 1 (RanGAP1) and Topoisomerase IIα, SUMO1 targets in somatic and/or germ cells, are SUMO1-ylated in mature human spermatozoa. DRP1 co-localises with SUMO1 in the mid-piece, whereas RanGAP1 and Topoisomerase IIα in the post-acrosomal region of the head. Both SUMO1 expression and co-localisation with the three proteins were significantly higher in morphologically abnormal sperm, suggesting that sumoylation represents a marker of defective sperm. DRP1 sumoylation at the mid-piece level was higher in the sperm of asthenospermic men. As in somatic cells, DRP1 sumoylation is associated with mitochondrial alterations, this protein may represent the link between SUMO and poor motility. As SUMO pathways are involved in responses to DNA damage, another aim of our study was to investigate the relationship between sumoylation and sperm DNA fragmentation (SDF). By flow cytometry, we demonstrated that SUMO1-ylation and SDF are correlated (r=0.4, P<0.02, n=37) and most sumoylated sperm shows DNA damage in co-localisation analysis. When SDF was induced by stressful conditions (freezing and thawing and oxidative stress), SUMO1-ylation increased. Following freezing and thawing, SUMO1-Topoisomerase IIα co-localisation and co-immunoprecipitation increased, suggesting an involvement in the formation/repair of DNA breakage.

Low testosterone syndrome protects from major adverse cardiovascular events in subjects at high cardiovascular burden

0,2 0,0 0,0 0,2 0,4 0,6 0,8 1,0 1-SPECIFICITY 0,0 0,2 0,4 0,6 0,8 1,0 cFT <225 pM/l T <12nM/l LOW TESTOSTERONE SYNDROME PROTECTS FROM MAJOR ADVERSE CARDIOVASCULAR EVENTS IN SUBJECTS AT HIGH CARDIOVASCULAR BURDEN E. Maseroli, G. Corona, G. Rastrelli, A. Sforza, G. Forti, E. Mannucci, M. Maggi Background. The role of testosterone (T) in cardiovascular (CV) health of men is controversial. Several data suggest that hypogonadism is associated with CV mortality but not morbidity. However, recent evidence shows that hypogonadal subjects treated with T replacement therapy have a higher incidence of major adverse CV events (MACE). The aim of this study is to analyze whether the gonadal status might predict MACE incidence according to the previous history of MACE, in a cohort of subjects complaining for sexual dysfunction. A consecutive series of 1687 patients was followed-up for a mean time of 4.3±2.6 years for new occurrence of MACE, detecting 139 events.

Sperm DNA fragmentation as assessed by TUNEL/PI: mean values in fertile men and intra individual variability

After matching for semen quality and age, sub/infertile men present greater amount of SDF than fertile ones. Such a difference is entirely due to the PI br SDF (Fig.2). Hence SDF, and in particular PI br SDF, is able to distinguish between fertile and sub/infertile subjects independently from age and semen quality. One limitation of this study is that we have no data on the female factor in the recruited infertile couples. It is possible that in a certain number of these couples, the infertility was due to a female factor and that the male partners was actually fertile. This would explain why the difference in SDF between the two groups is not so high.