The dogma of mitochondria as the major source of energy in supporting sperm motility should be critically reconsidered in the light of several experimental data pointing to a major role of glycolysis in mammalian spermatozoa. In this light, the reported positive correlation between the mitochondrial membrane potential (ΔΨm) and motility of ejaculated spermatozoa cannot be explained convincingly by an impaired mitochondrial ATP generation only. Evidence has been produced suggesting that, in human sperm, dysfunctional mitochondria represent the main site of generation of reactive oxygen species (ROS). Furthermore, in these organelles, a complex bidirectional relationship could exist between ROS generation and apoptosis-like events that synergize with oxidative stress in impairing sperm biological integrity and functions. Despite the activity of enzymatic and non-enzymatic antioxidant factors, human spermatozoa are particularly vulnerable to oxidative stress, which plays a major role in male factor infertility. The purpose of this article is to provide an overview of metabolic, oxidative and apoptosis-like inter-linkages of mitochondrial dysfunction and their reflections on human sperm biology.

Background: Mucosal healing (MH) evaluated by endoscopy is a novel target of therapy in UC as it is associated with improved long-term outcomes. It is defined based on the Mayo endoscopic score (MES), but it is still to define whether a value of MES 0 or 1 should be the target. The purpose of this paper is to present the results of a systematic review with meta-analysis which compares long-term outcomes of patients in steroid-free clinical remission with MES 0 with those with MES 1. Methods: A systematic electronic search of the literature was performed using Medline, Scopus, and CENTRAL through December 2020 (PROSPERO n:CRD42020179333). The studies concerned UC patients, in steroid-free clinical remission, with MES of 0 or 1, and with at least 12-months of follow-up. Results: Out of 4611 citations, 15 eligible studies were identified. Increases in clinical relapse among patients with MES 1 were observed in all the studies included in this review, suggesting that MES of 1 have a higher risk of relapse than a score of 0. MES 0 patients displayed a lower risk of clinical relapse (OR 0.33; 95% CI 0.26–0.43; I² 13%) irrespective of the follow-up time (12-months or longer). On the other hand, no differences were found comparing MES 0 versus MES 1 about the risk of hospitalization or colectomy. Conclusions: MES 0 is associated with a lower rate of clinical relapse than is MES 1. For this reason, MES 0, rather than MES 0–1, should be considered the therapeutic target for patients with UC.

Purpose: We aimed to evaluate whether and to what extent an association exists between male aging and worsening of semen parameters and to determine whether a threshold age can be identified above which the decline in semen quality becomes statistically significant. Methods: 2612 men (age: 16–56 years) attending an andrology outpatient clinic for semen analysis and clinical evaluation were studied. Semen analyses were performed according to the ongoing WHO-recommended procedures. Total motile count (TMC) and total progressive motile count (TPMC) were calculated by multiplying total sperm number by total motility and progressive motility, respectively. Results: Significant negative correlations were found between age and total motility (r = − 0.131, p < 0.0001), progressive motility (r = − 0.112, p < 0.0001), TPMC (r = − 0.042, p = 0.037), and normal sperm morphology (r = − 0.053, p = 0.007). All these associations persisted in multivariate regression models adjusted for abstinence time, smoking, history of male accessory gland infections, varicocele and the year in which semen analysis was performed. When comparisons were performed among quartiles of increasing age, the fourth quartile, corresponding to the age group > 40 years, was associated with a significant decrease in total and progressive motility. An earlier decline in the TPMC and percentage of normal forms was also observed. Conclusion: Advancing male age exhibits an independent association with a decrease in the percentage of motile and morphologically normal spermatozoa, with greater evidence from the age of > 40 years. Further studies are warranted to elucidate the mechanisms and clinical reflections of these associations.

Infertility is a potential side effect of radiotherapy and significantly affects the quality of life for adolescent cancer survivors. Very few studies have addressed in pubertal models the mechanistic events that could be targeted to provide protection from gonadotoxicity and data on potential radioprotective treatments in this peculiar period of life are elusive. In this study, we utilized an in vitro model of the mouse pubertal testis to investigate the efficacy of crocetin to counteract ionizing radiation (IR)-induced injury and potential underlying mechanisms. Present experiments provide evidence that exposure of testis fragments from pubertal mice to 2 Gy X-rays induced extensive structural and cellular damage associated with overexpression of PARP1, PCNA, SOD2 and HuR and decreased levels of SIRT1 and catalase. A twenty-four hr exposure to 50 μM crocetin pre- and post-IR significantly reduced testis injury and modulated the response to DNA damage and oxidative stress. Nevertheless, crocetin treatment did not counteract the radiation-induced changes in the expression of SIRT1, p62 and LC3II. These results increase the knowledge of mechanisms underlying radiation damage in pubertal testis and establish the use of crocetin as a fertoprotective agent against IR deleterious effects in pubertal period.

Angiotensin-converting enzyme 2 (ACE2) is a protein widely expressed in numerous cell types, with different biological roles mainly related to the renin-angiotensin system. Recently, ACE2 has been in the spotlight due to its involvement in the SARS-CoV-2 entry into cells. There are no data available regarding the expression of ACE2 and its short-ACE2 isoform at the protein level on human spermatozoa. Here, protein expression was demonstrated by western blot and the percentage of sperm displaying surface ACE2 was assessed by flow cytometry. Immunocytochemistry assays showed that full-length ACE2 was mainly expressed in sperm midpiece, while short ACE2 was preferentially distributed on the equatorial and post-acrosomal region of the sperm head. To our knowledge, this is the first study demonstrating the expression of protein ACE2 on spermatozoa. Further studies are warranted to determine the role of ACE2 isoforms in male reproduction.

Depression is the most prevalent psychological issue after a spinal cord injury (SCI) and is associated with noticeable disability, mortality and health expenditure. As SCI mainly occurs in sexually active men at a young age, and can lead to them suffering from an organic neurogenic erectile dysfunction (ED), we supposed that ED could be a major correlate of depressive status in men with SCI. As documented by a Beck Depression Inventory-II (BDI-II) score ≥14, depression was reported in 17 out of 57 men with a chronic SCI (29.8%). They exhibited a significantly higher prevalence of ED and a more severe bowel and bladder dysfunction when compared to the group without depression. At the multiple logistic regression analysis, depression showed a significant independent association with ED (OR = 19.0, 95% CI: 3.1, 203.3; p = 0.004) and, to a lesser extent, with a severe impairment of bowel and bladder function (OR = 0.84; 95% CI: 0.72, 0.94; p = 0.01). Depression was observed in 43.7% of men with ED and only in 12.0% of those without ED (p = 0.002). In conclusion, healthcare providers should give the right level of importance to the management of ED in men with SCI, as this represents a major independent correlate of depression, which, in turn, might hinder physical rehabilitation and exacerbate physical health issues related to SCI.