During the last decades the study of male infertility and the introduction of the assisted reproductive techniques (ARTs) has allowed to understand that normal sperm parameters do not always predict fertilization. Sperm genetic components could play an important role in the early stages of embryonic development. Based on these acquisitions, several epigenetic investigations have been developed on spermatozoa, with the aim of understanding the multifactorial etiology of male infertility and of showing whether embryonic development may be influenced by sperm epigenetic abnormalities. This article reviews the possible epigenetic modifications of spermatozoa and their effects on male fertility, embryonic development and ART outcome. It focuses mainly on sperm DNA methylation, chromatin remodeling, histone modifications and RNAs.

The aim of this experimental study was to evaluate the effects of nicotine on sperm motility and on nonconventional sperm parameters in vitro. Capacitated spermatozoa isolated from 10 normozoospermic, healthy, non-smoker men were evaluated. Spermatozoa were exposed to increasing concentrations of nicotine (0, 1, 10, and 100 nglml) for 3 and 24 hours. Progressive motility and the following nonconventional sperm parameters, evaluated by flow cytometry, were assessed: mitochondrial membrane potential, viability, phosphatidylserine externalization, late apoptosis, degree of chromatin compactness, and DNA fragmentation. Nicotine suppressed, in a concentration-dependent manner, sperm progressive motility starting from the lowest concentration used (1 ng/ml), Similarly, it reduced the percentage of viable spermatozoa and increased the number of spermatozoa in late apoptosis, with altered chromatin compactness, or DNA fragmentation already after 3 hours of incubation. These effects were observed at a concentration similar (100 nglml) to that found in the seminal plasma of smokers (70 ng/ml), with the exception of the effects on sperm DNA fragmentation whose significant effect was detected also at a lower concentration (10 ng/ml), Nicotine may be regarded as a noxious component of cigarette smoke on the male reproductive function.Cigarette smoking is a risk factor for the onset of male sexual and reproductive diseases even today despite this topic bring highly controversial. In particular, it seems to alter sperm function though the mechanism(s) are still not entirely clear. Indeed, the combustion of tobacco releases more than 4,000 chemicals; some of them in the gaseous phase (carbon monoxide, nitric oxide, ammonia, hydrocarbons, etc.), others, such as nicotine, in the particulate phase.Nicotine is an alkaloid, and in nature is found in a non-ionized form (lipophilic) in an alkaline environment and in an ionized form (hydrophilic) in an acid environment. Under physiological conditions (pH 7.3-7.5) because of its lipophilic form (31%), nicotine crosses the biological membranes and is absorbed by the mucous membranes and skin and more than 80% is metabolized in the liver, kidney, and lung. CYP2A6 is the main cytochrome involved in its metabolism and thus in its oxidation. Nicotine concentration in the saliva of a subject, who has just finished smoking a cigarette, is about 1.56 mg/ml, 100,000 times higher than concentration in the peripheral blood, while the concentration of nicotine absorbed is about 1 mg/cigarette. From the bloodstream, nicotine and its metabolites go into

Lifestyle, cigarette smoking and environmental pollution have a negative impact on male fertility. Therefore, the aim of this study was to evaluate the in-vitro effects of benzo-α-pyrene (BaP) and aryl hydrocarbon receptor (AHR) agonists on motility and bio-functional sperm parameters. We further assessed whether resveratrol (RES), an AHR antagonist and antioxidant molecule, had any protective effect. To accomplish this, 30 normozoospermic, healthy, non-smoker men not exposed to BaP were enrolled. Spermatozoa of 15 men were incubated with increasing concentrations of BaP to evaluate its effect and to establish its dose response. Then, spermatozoa of the 15 other men were incubated with BaP (15 µM/mL), chosen according to the dose-response and/or RES to evaluate its antagonistic effects. The effects of both substances were evaluated after 3 h of incubation on total and progressive sperm motility and on the following bio-functional sperm parameters evaluated by flow cytometry: Degree of chromatin compactness, viability, phosphatidylserine externalization (PS), late apoptosis, mitochondrial membrane potential (MMP), DNA fragmentation, degree of lipoperoxidation (LP), and concentrations of mitochondrial superoxide anion. Benzo-α-pyrene decreased total and progressive sperm motility, impaired chromatin compactness, and increased sperm lipoperoxidation and mitochondrial superoxide anion levels. All these effects were statistically significant at the lowest concentration tested (15 µM/mL) and they were confirmed at the concentration of 45 µM/mL. In turn, RES was able to counteract the detrimental effects of BaP on sperm motility, abnormal chromatin compactness, lipid peroxidation, and mitochondrial superoxide. This study showed that BaP alters sperm motility and bio-functional sperm parameters and that RES exerts a protective effect on BaP-induced sperm damage.

Varicocele is a common cause of sperm damage. Some studies showed higher concentration of seminal leukocytes in patients with varicocele. The aim of the study was to evaluate seminal leukocyte subpopulations in patients with varicocele. We enrolled 20 patients with varicocele and 20 age-matched healthy men. Sperm analysis was conducted according to the World Health Organization (WHO) 2010 criteria. We evaluated seminal leukocyte subpopulations and bio-functional sperm parameters by flow cytometry. Patients with varicocele had significantly lower sperm concentration and total number than controls. Regarding seminal leukocyte subpopulations, patients with varicocele had a significantly lower percentage of CD8+ and CD16+ leukocytes and a significantly higher percentage of CD4+ leukocytes than controls. As for bio-functional sperm parameters, we found that patients with varicocele had a significantly lower percentage of alive spermatozoa compared to the control group. These results may explain the increased level of cytokines in the seminal plasma of patients with varicocele.

Pediatric varicocele has an overall prevalence of 15%, being more frequent as puberty begins. It can damage testicular function, interfering with Sertoli cell proliferation and hormone secretion, testicular growth and spermatogenesis. Proper management has a pivotal role for future fertility preservation. The aim of this review was to discuss the diagnosis, management and treatment of childhood and adolescent varicocele from an endocrinologic perspective, illustrating the current evidence of the European Society of Pediatric Urology (ESPU), the European Association of Urology (EAU), the American Urological Association (AUA) and the American Society for Reproductive Medicine (ASRM) scientific societies. According to the ASRM/ESPU/AUA practice committee, the treatment of adolescent varicocele is indicated in the case of decreased testicular volume or sperm abnormalities, while it is contraindicated in subclinical varicocele. The recent EAS/ESPU meta-analysis reports that moderate evidence exists on the benefits of varicocele treatment in children and adolescents in terms of testicular volume and sperm concentration increase. No specific phenotype in terms of testicular volume cut-off or peak retrograde flow (PRF) is indicated. Based on current evidence, we suggest that conservative management may be suggested in patients with PRF < 30 cm/s, testicular asymmetry < 10% and no evidence of sperm and hormonal abnormalities. In patients with 10–20% testicular volume asymmetry or 30 < PRF ≤ 38 cm/s or sperm abnormalities, careful follow-up may ensue. In the case of absent catch-up growth or sperm recovery, varicocele repair should be suggested. Finally, treatment can be proposed at the initial consultation in painful varicocele, testicular volume asymmetry ≥ 20%, PRF > 38 cm/s, infertility and failure of testicular development.