Severe acute respiratory syndrome coronavirus (SARS-CoV-2) disease (COVID-19) appears to have a higher mortality rate in presence of comorbidities and in men. The latter suggests the presence of a ...possible sex-dependent susceptibility. An enzymatic system involved in this different predisposition could be represented by angiotensin converting enzyme 2 (ACE2). ACE2 is activated and down-regulated by the spike protein of the virus and allows the penetration of SARS-CoV-2 into epithelial cells and myocardium. Data on the experimental animal have shown that 17ß-estradiol increases the expression and activity of ACE2 in both adipose tissue and kidney. Spontaneously hypertensive male mice have a higher myocardial ACE2 expression than females and its levels decrease after orchiectomy. In addition to this first aspect, the recent evidence of an increased frequency of venous thromboembolism in patients with COVID-19 (a clinical element associated with a worse prognosis) calls the attention on the safety of treatment with testosterone, in particular in hypogonadal men with greater genetic predisposition. Evidence that sex hormones are able to modulate the expression of ACE2 could help in interpreting epidemiological results and in designing more appropriate intervention strategies. Moreover, the vitamin D deficiency in elderly men may be worthy of further study regarding the epidemiological aspects of this different susceptibility and lethality between sexes.
Male infertility affects half of infertile couples and, currently, a relevant percentage of cases of male infertility is considered as idiopathic. Although the male contribution to human ...fertilization has traditionally been restricted to sperm DNA, current evidence suggest that a relevant number of sperm transcripts and proteins are involved in acrosome reactions, sperm‒oocyte fusion and, once released into the oocyte, embryo growth and development. The aim of this review is to provide updated and comprehensive insight into the molecular biology of spermatogenesis, including evidence on spermatogenetic failure and underlining the role of the sperm-carried molecular factors involved in oocyte fertilization and embryo growth. This represents the first step in the identification of new possible diagnostic and, possibly, therapeutic markers in the field of apparently idiopathic male infertility.
Benign prostatic hyperplasia (BPH) is very common in aging men and causes lower urinary tract symptoms (LUTS), which decrease health-related quality of life. A number of evidence suggests that other ...than ageing, modifiable factors, such as increasing prostate volume, obesity, diet, dyslipidemia, hormonal imbalance, hypertension, metabolic syndrome, alcohol, and smoking, also contribute to the development of BPH and/or LUTS. More recently, erectile dysfunction (ED) has been linked to LUTS/BPH as a part of this syndrome, suggesting that patients with BPH or LUTS easily develop ED, and that LUTS/BPH symptoms often coexist with ED. This article focuses on the epidemiology and risk factors of the combined phenotype LUTS/BPH - ED.
Abstract Male infertility is a major public health concern globally with unknown etiology in approximately half of cases. The decline in total sperm count over the past four decades and the parallel ...increase in childhood obesity may suggest an association between these two conditions. Here, we review the molecular mechanisms through which obesity during childhood and adolescence may impair future testicular function. Several mechanisms occurring in obesity can interfere with the delicate metabolic processes taking place at the testicular level during childhood and adolescence, providing the molecular substrate to hypothesize a causal relationship between childhood obesity and the risk of low sperm counts in adulthood.
This systematic review and meta-analysis summarize the difference in the methylation of the
gene in patients with abnormal versus normal conventional sperm parameters. It also evaluates the effects ...of age and sperm concentration on
methylation in spermatozoa using meta-regression analysis. It was performed according to the MOOSE guidelines for meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). The quality of the evidence reported in the studies included was assessed using the Cambridge Quality Checklists. A total of 11 articles met our inclusion criteria. Quantitative analysis showed that
methylation levels were significantly lower in the group of infertile patients than in fertile controls. The reduction in methylation was much more pronounced in patients with oligozoospermia (alone or associated with other sperm parameter abnormalities) and in those with recurrent pregnancy loss. Meta-regression analysis showed the results to be independent of both patient age and sperm concentration. Therefore, the
methylation pattern should be evaluated among couples accessing assisted reproductive techniques (ART), in order to gain prognostic information on ART outcome and offspring health.
Obesity is a widespread disease that is associated with numerous and serious comorbidities. These include metabolic syndrome, diabetes mellitus, cardiovascular-cerebrovascular disease, hypertension, ...obstructive sleep apnea syndrome, cancer, and sexual and hormonal disorders. The treatment of obesity has therefore become a goal of great clinical and social relevance. Among the therapeutic strategies against obesity, resveratrol has aroused great interest. This polyphenol has anticancer and antioxidant properties and cytoprotective and anti-inflammatory effects. Other favorable effects attributed to resveratrol are anti-lipid, anti-aging, anti-bacterial, anti-viral, and neuroprotective actions. Administration of resveratrol appears to improve the metabolic profile in obese and/or insulin-resistant patients. This article aims to review the main results of clinical studies evaluating the effects of administering resveratrol alone in overweight/obese patients.
Although the prevalence of sub-infertility in diabetic patients in childbearing age is known, the mechanisms by which diabetes mellitus (DM) causes male infertility are not completely explained. This ...detrimental effect is achieved with a variety of mechanisms that include pre-testicular, testicular, and post-testicular pathogenetic moments and can be different in type 1 diabetes mellitus (DM1) and type 2 diabetes mellitus (DM2) patients because of type of diabetes, duration of disease, and glycemic metabolic compensation. Aim of this study was to evaluate whether diabetic disease can be considered a risk factor for infertility considering the etiopathogenetic differences between DM1 and DM2 on sperm function. We enrolled 38 DM1 patients and 55 DM2 patients with idiopathic infertility history >12 months, and 100 healthy fertile subjects. The following outcomes were evaluated in optical microscopy and flow cytometry: sperm function (by conventional and biofunctional sperm parameters) and signs of urogenital infection/inflammation (by sperm leukocyte concentrations and indices of oxidative stress). Moreover, an andrological evaluation (by didymo-epididymal ultrasound evaluation, serum total testosterone, LH, and FSH measurements) was performed in DM1 and DM2 patients compared to controls. Diabetic patients showed a higher risk of becoming infertile and the pathophysiological mechanisms of damage were different in DM1 and DM2. Conventional sperm parameters of diabetic patients are worse than controls (
< 0.05). The DM2 caused an inflammatory condition with increased oxidative stress resulting in decreased sperm vitality and increased sperm DNA fragmentation. DM1 altered epididymal voiding causing low ejaculate volume and mitochondrial damage resulting in decreased sperm motility. These findings and evidences support the contention that DM could be regarded as cause of male infertility suggesting that the prevention of diabetic disease in DM2 and the follow-up of seminal parameters in DM1 could prevent fertility decline in these categories of patients.
A large proportion of patients with idiopathic spermatogenic failure (SPGF; oligozoospermia or nonobstructive azoospermia NOA) do not receive a diagnosis despite an extensive diagnostic workup. ...Recent evidence has shown that the etiology remains undefined in up to 75% of these patients. A number of genes involved in germ-cell proliferation, spermatocyte meiotic divisions, and spermatid development have been called into play in the pathogenesis of idiopathic oligozoospermia or NOA. However, this evidence mainly comes from case reports. Therefore, this study was undertaken to identify the molecular causes of SPGF. To accomplish this, 15 genes (USP9Y, NR5A1, KLHL10, ZMYND15, PLK4, TEX15, TEX11, MEIOB, SOHLH1, HSF2, SYCP3, TAF4B, NANOS1, SYCE1, and RHOXF2) involved in idiopathic SPGF were simultaneously analyzed in a cohort of 25 patients with idiopathic oligozoospermia or NOA, accurately selected after a thorough diagnostic workup. After next-generation sequencing (NGS) analysis, we identified the presence of rare variants in the NR5A1 and TEX11 genes with a pathogenic role in 3/25 (12.0%) patients. Seventeen other different variants were identified, and among them, 13 have never been reported before. Eleven out of 17 variants were likely pathogenic and deserve functional or segregation studies. The genes most frequently mutated were MEIOB, followed by USP9Y, KLHL10, NR5A1, and SOHLH1. No alterations were found in the SYCP3, TAF4B, NANOS1, SYCE1, or RHOXF2 genes. In conclusion, NGS technology, by screening a specific custom-made panel of genes, could help increase the diagnostic rate in patients with idiopathic oligozoospermia or NOA.
Follicle-stimulating hormone (FSH) represents a therapeutic option in normogonadotropic patients with idiopathic oligozoospermia. The aim of this review was to evaluate the possible dose- and ...drug-dependent efficacy of FSH treatment on conventional sperm parameters. We performed a comprehensive systematic review via a meta-analysis of all available randomized controlled trials, in which FSH administration was compared with placebo or no treatment when administered to normogonadotropic patients with idiopathic oligozoospermia. Of the 971 articles that were retrieved, 5 were finally included, including a total of 372 patients and 294 controls. Overall, FSH treatment was effective in ameliorating the sperm concentration, total count, progressive motility, but not normal forms. On the basis of the weekly dosage, the studies were classified into those using low (175-262.5 IU per week), intermediate (350-525 IU per week), and high (700-1050 IU per week) doses. At low doses, FSH improved only sperm motility. At intermediate doses, FSH ameliorated sperm concentration and morphology. Total sperm count and progressive motility showed a trend toward the increase. At high doses, FSH increased sperm concentration, total sperm count, and progressive motility. Sperm morphology showed a trend toward the increase. Finally, both highly purified FSH (hpFSH) and recombinant human FSH (rhFSH) improved sperm concentration, total sperm count, progressive motility, but not morphology. No different efficacy was observed between these two preparations. This meta-analysis provides evidence in favor of high FSH doses. The FSH efficacy was not related to the preparation type (recombinant vs highly purified). Further studies are needed to evaluate the effectiveness of long-standing treatment regimes.
As the "-omic" technology has largely developed, its application in the field of medical science seems a highly promising tool to clarify the etiology, at least in part, of the so-called idiopathic ...male infertility. The seminal plasma (SP) is made-up of secretions coming from the male accessory glands, namely epididymis, seminal vesicles, and prostate. It is not only a medium for sperm transport since it is able to modulate the female reproductive environment and immunity, to allow the acquisition of sperm competence, to influence the sperm RNA content, and even embryo development. The aim of this systematic review was to provide an updated and comprehensive description of the main transcripts and proteins reported by transcriptome and proteome studies performed in the human SP of patients with idiopathic infertility, in the attempt of identifying possible candidate molecular targets. We recurrently found that micro RNA (miR)-34, miR-122, and miR-509 are down-regulated in patients with non-obstructive azoospermia (NOA) and oligozoospermia compared with fertile controls. These molecules may represent interesting targets whose predictive role in testicular sperm extraction (TESE) or assisted reproductive techniques (ART) outcome deserves further investigation. Furthermore, according to the available proteomic studies, ECM1, TEX101, lectingalactoside-binding andsoluble 3 binding protein (LGALS3BP) have been reported as accurate predictors of TESE outcome. Interestingly, ECM1 is differently expressed in patients with different ART outcomes. Further prospective, ample-sized studies are needed to validate these molecular targets that will help in the counseling of patients with NOA or undergoing ART.
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