The Smoky Impact of Nicotinic Acetylcholine Receptors on Testicular Function.

Smoking habits (from classic cigarettes to e-cigarettes and heated tobacco) are a relatively common finding in the medical histories of couples referred to fertility centers. Tobacco smoke and e-cigarettes may deliver many substances with known harmful effects on both general and reproductive health, including nicotine. Nicotinic Acetylcholine receptors (nAChRs) form a heterogeneous family of ion channels that are differently expressed in different tissues. According to the homomeric or heteromeric combination of at least five different subunits (named from α to ε), they have peculiar pharmacological and biophysical properties. nAChRs respond to the neurotransmitter acetylcholine, which influences a number of physiological functions not restricted to neurons and plays an important role in the structure and function of non-neuronal tissues such as the testis. nAChRs are also the target of Nicotine, the active element responsible for tobacco addiction. This review summarizes recent findings on the involvement of nAChRs in testicular physiology, highlighting the effects of nicotine exposure observed in animal studies and clinical settings. We will discuss the latest data on fertility outcomes and the implications for understanding nAChR functions in reproductive health.

Follicle-stimulating hormone receptor gene polymorphisms influence Body Mass Index, metabolism, and bone mineral density in postmenopausal women.

BACKGROUND: Covering a significant part of a woman's life, the postmenopausal phase is often associated with the onset of obesity, metabolic dysfunction, osteoporosis, and their most disabling complications. In this context, scant evidence from both preclinical and clinical studies suggests that single nucleotide polymorphisms (SNPs) of the follicle-stimulating hormone receptor (FSHR) gene might be involved in the etiopathogenesis of these conditions, posing them as possible molecular predictors of their development. Therefore, this study aimed to evaluate the role of the FSHR gene SNPs c.2039A>G and c.-29 G>A on Body Mass Index (BMI), metabolic parameters, and bone metabolism in postmenopausal women. METHODS: To achieve this goal, 49 postmenopausal Caucasian women aged from 45 to 80 years and with no factors known to influence metabolism and/or bone mineral density (BMD) were enrolled and assessed for their medical history, medical family history, anthropometric parameters and hormonal, metabolic and lipid profiles, and BMD. Then, they were genotyped for the FSHR gene SNPs c.2039A>G and c.-29G>A. Finally, the resulting data were classified according to woman's genotypes and subjected to statistical analysis. RESULTS: No significant differences were found between the distributions of most endpoint parameters examined by genotype. However, none of the women with the c.2039A>G FSHR GG gene SNP were affected by obesity and had the highest lumbar BMD z-score within the cohort. Additionally, those with the FSHR c.-29G>A AA genotype had the lowest serum glucose levels. CONCLUSIONS: This preliminary study suggests that the FSHR c.2039A>G GG SNP, which is associated with reduced sensitivity of the FSHR, may have a protective role against obesity, offering further evidence for the possible association among FSH, FSHR polymorphisms, and insulin metabolism.

The additional value of ultrasound markers in the diagnosis of polycystic ovary syndrome.

OBJECTIVE: To study the value of current definitions for follicle number per ovary and ovarian volume in the diagnosis of polycystic ovary syndrome (PCOS). DESIGN: Cross-sectional study. SETTING: University tertiary care center. PATIENT(S): Women diagnosed with PCOS after standardized screening were eligible for inclusion in the PCOS group. Women without PCOS who underwent the same screening, had regular menstrual cycles, normal hormonal values, and no other endocrine pathology were eligible for inclusion. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Follicle number per ovary and ovarian volume in women with PCOS, stratified by age. Linear regression models to investigate the influence of body mass index (BMI) on follicle number per ovary and ovarian volume. Differences in follicle number per ovary and ovarian volume between the PCOS phenotypes and the additional value of ovarian volume compared with follicle number per ovary. RESULT(S): A total of 2,492 women (16-50 years) with PCOS and 152 women without PCOS were included. Most women with PCOS up to age of 35 exhibit a follicle number per ovary ≥20 (87.8%-100%) (using an ultrasound transducer ≥8 MHz) or ≥12 (95.1%-98.6%) (using a transducer <8 MHz), followed by a decline in follicle number per ovary >35 years. Median ovarian volume was below the 10 mL cutoff in every age group, for both ultrasound transducers. Follicle number per ovary and ovarian volume were higher in women with PCOS compared with women without PCOS in every age category. In our cohort, 13/2,297 women with PCOS (0.6%) would not have received the diagnosis if ovarian volume was not considered a marker for polycystic ovarian morphology. For both ultrasound transducers, women with phenotype A (ovulatory dysfunction + hyperandrogenism + polycystic ovarian morphology) exhibited the highest follicle number per ovary and ovarian volume, followed by phenotype D (ovulatory dysfunction + polycystic ovarian morphology), then phenotype C (hyperandrogenism + polycystic ovarian morphology), and then phenotype B (ovulatory dysfunction + hyperandrogenism). No clinically significant correlation between BMI and follicle number per ovary or ovarian volume was observed. CONCLUSION(S): Criteria to define follicle number per ovary should be established per age category, as follicle number per ovary decreases with age. Ovarian volume shows a less clear decline with age and has a lower discriminative power, and therefore could be excluded from the diagnostic criteria. Follicle number per ovary does not need to be stratified by BMI.

Gene-environment interaction in functional hypothalamic amenorrhea.

Functional hypothalamic amenorrhea (FHA) is a common cause of amenorrhea and chronic anovulation in adolescent girls and young women, diagnosed after excluding other organic causes. It is commonly associated with calorie restriction, excessive physical exercise, and psychosocial stress. These stressors alter the pulsatile secretion of gonadotropin-releasing hormone, leading to a chronic condition of hypoestrogenism and significant health consequences. Recent evidence has highlighted a genetic predisposition to FHA that could explain interindividual variability in stress response. Indeed, not all women experience FHA in response to stress. Rare variants in genes associated with idiopathic hypogonadotropic hypogonadism have been identified in women with FHA, suggesting that these mutations may contribute to an increased susceptibility of women to the trigger of stress exposure. FHA appears today as a complex disease resulting from the combination of genetic predisposition, environmental factors, and epigenetic changes. Furthermore, the genetic background of FHA allows for the hypothesis of a male counterpart. Despite the paucity of data, preliminary findings indicate that an equivalent condition of FHA exists in men, warranting further investigation. This narrative review aims to summarize the recent genetic evidence contributing to the pathophysiology of FHA and to raise awareness on a possible male counterpart.

Body Image and Other Mood Vulnerabilities in Adolescents with Polycystic Ovary Syndrome and Metabolic Alterations.

INTRODUCTION: Psychological vulnerability is a relevant component of polycystic ovarian syndrome (PCOS), but it is still under-explored, especially during adolescence. The aim of this study was to describe a selection of psychometric characteristics in a clinical sample of Italian adolescents with PCOS. Moreover, we reported the associations of body image, eating attitudes, and mood with metabolic features. METHODS: Our sample included 128 adolescent girls (age range: 14-19 years) with PCOS. Validated psychometric questionnaires were administered: State Anxiety Inventory (STAI), Beck Depression Inventory (BDI), Body Attitude Test (BAT), Bulimia Investigation Test (BITE), Eating Attitudes Test (EAT), and Perceived Stress Scale (PSS). RESULTS: Anxiety was the most prevalent mood disorder (63.1% trait anxiety and 57% state anxiety). Our cohort also showed a high prevalence of depression (39.1%), body image dissatisfaction (49.2%), disordered eating (11.7%), and bulimic risk (41.4%). PCOS adolescents with obesity and insulin resistance (IR) had statistically significant higher body image distress compared to those with normal weight and without IR (p < 0.001). The Sobel test for mediation showed that body image dissatisfaction mediates the relationship between state anxiety and bulimic risk (Z = 3.42, p < 0.001) and between depression and bulimic risk (Z = 4.59, p < 0.001). CONCLUSIONS: A considerable number of patients with PCOS experience psychological disorders during adolescence. IR and obesity play a role in the distress associated with body image, further contributing to psychological vulnerability, especially in the bulimic domain. A comprehensive biopsychosocial approach in adolescents with PCOS represents the basis for effectively managing and preventing complications arising from both psychological and biological disorders in adulthood.

Thyroid diseases and female sexual dysfunctions.

INTRODUCTION: Female sexual dysfunctions (FSDs) have received little attention in the context of thyroid diseases, despite the high prevalence of both conditions. OBJECTIVES: This review aims to update and summarize the state of knowledge on the association between thyroid diseases and FSDs and to investigate the complex mechanisms through which thyroid hormone imbalance can impact female sexual health in the context of the biopsychosocial model. METHODS: A comprehensive literature search was performed through the PubMed, MEDLINE, and Scopus databases, using the following keywords: "female sexual function," "sexual dysfunction," "hypoactive sexual desire disorder," "thyroid disease," "thyroiditis," "hypothyroidism," and "hyperthyroidism." RESULTS: To date, well-designed studies that describe the relationship between FSDs and thyroid disorders are lacking. However, despite the limitations on available studies, current data indicate that sexual alterations are frequently associated with thyroid diseases in women. A complex interplay of direct and indirect hormonal and nonhormonal mechanisms has been hypothesized, including hormonal changes, neurotransmitter imbalance, reduced nitric oxide release, mood disorders, and other systemic consequences of both hypothyroidism and hyperthyroidism. Thyroid hormone receptors have also been identified in the genitourinary system. CONCLUSIONS: In a clinical setting, physicians should investigate the sexuality of patients consulting for thyroid disease. At the same time, an evaluation of thyroid function should be performed in patients presenting with FSD, especially after menopause, when the risk of thyroid diseases and FSDs increases strongly.

In-Vitro Effects of Perfluorooctanoic Acid on Human Sperm Function: What Are the Clinical Consequences?

Background: Lifestyle and environmental pollution harm male fertility. Perfluoroalkyl substances (PFAS) are bio-accumulates in the environment as well as in several human tissues, and one of the most common PFAS is perfluorooctanoic acid (PFOA). Therefore, this study aimed to evaluate the in vitro effects of PFOA with hydrophobic and waterproofing properties on motility and bio-functional sperm parameters. Methods: To accomplish this, 50 healthy men with normozoospermia and not exposed to high doses of PFAS were enrolled. Their spermatozoa were incubated for 3 h with increasing concentrations of PFOA (0, 0.01, 0.1, and 1 mM) to evaluate its effects. In particular, we evaluated the effects of PFOA on total and progressive sperm motility and, by flow cytometry, on the following bio-functional sperm parameters: degree of chromatin compactness, viability, early and late apoptosis, mitochondrial membrane potential, the degree of lipoperoxidation, and concentrations of mitochondrial superoxide anion. Results: The results showed that PFOA decreased both total and progressive sperm motility, impaired chromatin compactness, and increased sperm lipid peroxidation and mitochondrial superoxide anion levels. Conclusions: This study showed that PFOA alters several sperm parameters and thus it may play a negative role in male fertility.

Age-related Curves of AMH Using the Gen II, the picoAMH, and the Elecsys Assays in Women With Polycystic Ovary Syndrome.

CONTEXT: Several challenges still exist to adopt the anti-müllerian hormone (AMH) as a marker of polycystic ovary morphology, as included in the recently updated international guideline. Although different evaluations of age- and assay-specific reference ranges have been published in the past few years, these studies have mainly been conducted in normo-ovulatory or infertile women. OBJECTIVE: To develop an age-specific percentile distribution of AMH in patients with polycystic ovary syndrome (PCOS) measured by 3 different assays. DESIGN: Retrospective cross-sectional study. PATIENTS: A total of 2725 women aged 20 to 40 years with PCOS diagnosis were included. INTERVENTIONS: Serum AMH measurement by the Gen II (Beckman Coulter), the picoAMH (Ansh Labs), and the Elecsys (Roche) assays. MAIN OUTCOME MEASURES: Age-specific percentile curves for all the assays and correlations between AMH, clinical, hormonal, and ultrasound characteristics. RESULTS: Age-related nomograms for the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles of AMH were calculated using the Lambda-Mu-Sigma method for all the assays. AMH levels were significantly different between PCOS phenotypes. AMH levels were positively correlated to LH, LH/FSH ratio, testosterone, androstenedione, free androgen index, mean follicular number, and mean ovarian volume. CONCLUSION: To our knowledge, this is the first study reporting age-specific percentile nomograms of serum AMH levels measured by the Gen II, the picoAMH, and the Elecsys assays in a large population of women with PCOS. These findings may help to interpret AMH levels in patients with PCOS and facilitate the use of AMH as a diagnostic tool across age ranges.

Does Sperm SNRPN Methylation Change with Fertility Status and Age? A Systematic Review and Meta-Regression Analysis.

Background: The Small Nuclear Ribonucleoprotein Polypeptide N (SNRPN) gene is a paternally expressed imprinted gene, whose abnormal methylation appears to be associated with syndromes associated with the use of assisted reproductive techniques (ART), such as Angelman and Prader-Willi. Data present in the literature suggest the association between aberrant sperm SNRPN gene methylation and abnormal sperm parameters. The latest meta-analysis on the methylation pattern of this gene in spermatozoa of infertile patients published in 2017 reported a higher degree of methylation in the spermatozoa of infertile patients compared to fertile controls. Objectives: Here we provide an updated and comprehensive systematic review and meta-analysis of the sperm methylation pattern of the SNRPN gene in patients with abnormal sperm parameters/infertility compared to men with normal sperm parameters/fertile. For the first time in the literature, we performed a meta-regression analysis to evaluate whether age or sperm concentration could influence the methylation status of this gene at the sperm level. Methods: This meta-analysis was registered in PROSPERO (n. CRD42023397056). The Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P) and the MOOSE guidelines for meta-analyses and systematic reviews of observational studies were strictly followed in our meta-analysis. According to our Population Exposure Comparison Outcome (PECO) question, we included data from original articles assessing the levels of SNRPN gene methylation at the sperm level in infertile patients or patients with abnormalities in one or more sperm parameters compared to fertile or normozoospermic men. Results: Only six of 354 screened studies were included in the quantitative synthesis. Our analysis showed significantly higher levels of SNRPN gene methylation in patients compared to controls. However, significant heterogeneity was found between studies. In sensitivity analysis, no studies were sensitive enough to skew the results. The Egger test showed no publication bias. In the meta-regression analysis, the results were independent of age and sperm concentration in the overall population. The same results were found in the control group. However, when analyzing the patient group, a direct correlation was found between SNRPN methylation and age, indicating that the degree of methylation of the SNRPN gene increases with advancing age. Conclusions: Fertility status or abnormality of sperm parameters is associated with a change in the methylation pattern of the SNRPN gene, with higher levels found in infertile patients or those with abnormal sperm parameters compared to fertile men or men with normal sperm parameters. In the group of infertile patients/patients with abnormal sperm parameters, age was directly correlated to the degree of SNRPN methylation, highlighting the presence of a mechanism that explains the age-related altered sperm quality and the risk of ART. Despite some limitations present in the analyzed studies, our results support the inclusion of SNRPN methylation in the genetic panel of prospective studies aimed at identifying the most representative and cost-effective genes to analyze in couples who want to undergo ART.

Antioxidants for male infertility: therapeutic scheme and indications. A retrospective single-center real-life study.

BACKGROUND: This single-center real-life study was conducted to evaluate the most effective combination of nutraceuticals and the most appropriate indications for the treatment of male infertile patients. METHODS: Infertile patients aged 20-55 years were treated with a combination of antioxidants (Androlen®; Enfarma, Misterbianco, Catania, Italy) (group A), with Androlen® (Enfarma) and a mixture of fibrinolytic molecules (Lenidase®, Enfarma) (group B), or Androlen® (Enfarma) and other molecules different from those used for the patients of the group B (group C). Patients were also subdivided according to the presence of varicocele, mild testicular hypotrophy, idiopathic infertility, and chronic male accessory gland infection. RESULTS: Forty-three patients were enrolled. In the overall analysis, only progressive motility significantly improved after therapy. Subgroup analysis showed a significant increase in progressive motility, total motile sperm count (TMSC), and in the percentage of alive spermatozoa after treatment in the group A. Progressive motility improved significantly in patients with varicocele, while the TMSC in patients with varicocele and those with idiopathic infertility. The percentage of alive spermatozoa increased in patients with testicular hypotrophy. CONCLUSIONS: Treatment with antioxidants increased progressive sperm motility, especially in patients with varicocele or idiopathic infertility.

The Role of Irisin throughout Women's Life Span.

Since its discovery, much attention has been drawn to irisin's potential role in metabolic and reproductive diseases. This narrative review summarizes and updates the possible role played by this fascinating molecule in different physiological (puberty and menopause) and pathological (polycystic ovary syndrome (PCOS), functional hypothalamic amenorrhea (FHA), endometriosis, and gestational diabetes) conditions that can affect women throughout their entire lives. Irisin appears to be an important factor for the hypothalamic-pituitary-gonadal axis activation, and appears to play a role in the timing of puberty onset. Serum irisin levels have been proposed as a biomarker for predicting the future development of gestational diabetes (GDM). Its role in PCOS is still controversial, although an "irisin resistance" mechanism has been hypothesized. In addition to its impact on metabolism, irisin also appears to influence bone health. Irisin levels are inversely correlated with the prevalence of fractures in postmenopausal women. Similar mechanisms have also been postulated in young women with FHA. In clinical settings, further controlled, prospective and randomized clinical trials are needed to investigate the casual relationship between irisin levels and the conditions described and, in turn, to establish the role of irisin as a prognostic/diagnostic biomarker or a therapeutic target.

Testosterone replacement therapy and vascular thromboembolic events: a systematic review and meta-analysis.

ABSTRACT: To evaluate the relationship between testosterone replacement therapy (TRT) and arterial and/or venous thrombosis in patients with pre-treatment total testosterone (TT) <12 nmol l-1, we performed a meta-analysis following the Population Intervention Comparison Outcome model. Population: men with TT <12 nmol l-1 or clear mention of hypogonadism in the inclusion criteria of patients; intervention: TRT; comparison: placebo or no therapy; outcomes: arterial thrombotic events (stroke, myocardial infarction [MI], upper limbs, and lower limbs), VTE (deep vein thrombosis [DVT], portal vein thrombosis, splenic thrombosis, and pulmonary embolism), and mortality. A total of 2423 abstracts were assessed for eligibility. Twenty-four studies, including 14 randomized controlled trials (RCTs), were finally included, with a total of 4027 and 310 288 hypotestosteronemic male patients, from RCTs and from observational studies, respectively. Based on RCT-derived data, TRT did not influence the risk of arterial thrombosis (odds ratio [OR] = 1.27, 95% confidence interval [CI]: 0.47-3.43, P = 0.64), stroke (OR = 1.34, 95% CI: 0.09-18.97, P = 0.83), MI (OR = 0.51, 95% CI: 0.11-2.31, P = 0.39), VTE (OR = 1.42, 95% CI: 0.22-9.03, P = 0.71), pulmonary embolism (OR = 1.38, 95% CI: 0.27-7.04, P = 0.70), and mortality (OR = 0.70, 95% CI: 0.20-2.38, P = 0.56). Meanwhile, when only observational studies are considered, a significant reduction in the risk of developing arterial thrombotic events, MI, venous thromboembolism, and mortality was observed. The risk for DVT remains uncertain, due to the paucity of RCT-based data. TRT in men with TT <12 nmol l-1 is safe from the risk of adverse cardiovascular events. Further studies specifically assessing the risk of DVT in men on TRT are needed.

Sperm Mesoderm Specific Transcript Gene Methylation Status in Infertile Patients: A Systematic Review and Meta-Analysis.

PURPOSE: The mesoderm specific transcription (MEST) gene is a paternally expressed imprinted gene that appears to play a role in embryo survival. The latest meta-analysis on MEST methylation pattern in spermatozoa of infertile patients found higher methylation in spermatozoa from infertile patients than fertile controls. To provide an updated and comprehensive systematic review and meta-analysis on the MEST gene methylation pattern in patients with abnormal sperm parameters compared to men with normal parameters. MATERIALS AND METHODS: This meta-analysis was registered in PROSPERO (CRD42023397056) and performed following the MOOSE guidelines for Meta-analyses and Systematic Reviews of Observational Studies and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). Only original articles evaluating MEST gene methylation in spermatozoa from patients with infertility or abnormalities in one or more sperm parameters compared to fertile or normozoospermic men were included. RESULTS: Of 354 abstracts evaluated for eligibility, only 6 studies were included in the quantitative synthesis, involving a total of 301 patients and 163 controls. Our analysis showed significantly higher levels of MEST gene methylation in patients compared with controls (standard mean difference [SMD] 2.150, 95% confidence interval [CI] 0.377, 3.922; p=0.017), although there was significant heterogeneity between studies (Q-value=239.90, p<0.001; I²=97.91%). No significant evidence of publication bias was found, although one study was sensitive enough to skew the results, leading to a loss of significance (SMD 1.543, 95% CI -0.300, 3.387; p=0.101). In meta-regression analysis, we found that the results were independent of both ages (p=0.6519) and sperm concentration (p=0.2360). CONCLUSIONS: Sperm DNA methylation may be associated with epigenetic risk in assisted reproductive techniques (ART). The MEST gene could be included in the genetic panel of prospective studies aimed at identifying the most representative and cost-effective genes to be analyzed in couples undergoing ART.

Lifestyle and sexual habits of students in a Southern Italian region.

BACKGROUND: Incorrect or harmful lifestyle during youth may impact negatively gonadal function later in life. To reduce the development of risky behaviors a series of health prevention and intervention campaigns have been conducted in Italy. The present study is part of a Sicily Region (Italy) health surveillance program that was carried out on a sample of late adolescents. METHODS: Between March 2022 to December 2022, we enrolled 718 adolescents (15-26 years old) attending the last two years of high school (278 males and 440 females) in the districts of Syracuse, Ragusa, Catania, and Agrigento (Sicily, Italy). All adolescents were invited to complete a questionnaire that explored their lifestyles and the student's knowledge of sexually transmitted diseases (STDs) and the main andrological diseases. RESULTS: Our analysis revealed that 43% of students smoke cigarettes, with a similar gender distribution; one-third of the students use illicit drugs, with a higher prevalence of males than females. More than two-thirds of youngsters reported drinking alcohol with a statistically significant difference between genders. 68.2% of students do not have sexual difficulties and males have a greater tendency to sexual promiscuity than females and only about half of them use condoms. 92% of students surf the Internet every day; boys tend to visit pornographic sites more often than girls. CONCLUSIONS: This survey revealed statistically significant differences between the two genders in terms of lifestyle and sexual habits. In particular, the survey shows that the prevalence of risky behaviour is still extremely high among late adolescents and young adults and that much still needs to be done in terms of prevention and information. Adequate prevention campaigns, to be proposed in the early years of adolescence, should be initiated in order to provide youngsters with adequate preparation in terms of healthy lifestyle habits.

Bisphenols and perfluoroalkyls alter human stem cells integrity: A possible link with infertility.

Bisphenols and Perfluoroalkyls are chemical compounds widely used in industry known to be endocrine disruptors (EDs). Once ingested through contaminated aliments, they mimic the activity of endogenous hormones leading to a broad spectrum of diseases. Due to the extensive use of plastic in human life, particular attention should be paid to antenatal exposure to Bisphenols and Perfluoroalkyls since they cross the placental barrier and accumulates in developing embryo. Here we investigated the effects of Bisphenol-A (BPA), Bisphenol-S (BPS), perfluorooctane-sulfonate (PFOS) and perfluorooctanoic-acid (PFOA), alone or combined, on human-induced pluripotent stem cells (hiPSCs) that share several biological features with the stem cells of blastocysts. Our data show that these EDs affect hiPSC inducing a great mitotoxicity and dramatic changes in genes involved in the maintenance of pluripotency, germline specification, and epigenetic regulation. We also evidenced that these chemicals, when combined, may have additive, synergistic but also negative effects. All these data suggest that antenatal exposure to these EDs may affect the integrity of stem cells in the developing embryos, interfering with critical stages of early human development that might be determinant for fertility. The observation that the effects of exposure to a combination of these chemicals are not easily foreseeable further highlights the need for wider awareness of the complexity of the EDs effects on human health and of the social and economic burden attributable to these compounds.

Red Wine and Sexual Function in Men: An Original Point of View.

Red wine is a rich source of nutrients whose biological properties have inspired numerous scientific studies. Indeed, it has been widely reported that there is a correlation between the positive health effects of moderate consumption of red wine and its phenolic content, which, due to its antioxidant activity, has proved to be useful in the improvement of various diseases, such as cardiovascular diseases, metabolic syndrome, cognitive disorders, depression, and cancer. It is a common opinion that the antioxidant activity of red wine is to be ascribed to its entire content of polyphenols, which act synergistically and not as a single component. Furthermore, this health-promoting effect of red wine can also be linked to its ethanol content, which has shown a wide array of biological properties. Beyond this evidence, very little is known about a possible correlation between moderate consumption of red wine and male sexual function. This brief review aimed to evaluate the effects of moderate consumption of red wine on erectile function. To accomplish this, Pubmed and Google Scholar databases were searched to retrieve the most relevant studies on this topic. The evidence so far collected has shown that red wine, if consumed in moderation, can be potentially beneficial for patients with erectile dysfunction as well as can positively influence reproductive function through mechanisms that depend on the vasorelaxant properties of red wine and its antioxidant properties.

Mechanisms Suggesting a Relationship between Vitamin D and Erectile Dysfunction: An Overview.

Vitamin D deficiency (VDD) and erectile dysfunction (ED) heavily burden the male population. The higher prevalence of both conditions in the elderly suggests a possible relationship between the two conditions. In addition, in vitro, animal, and human studies have revealed several mechanisms that may relate VDD to ED. The main mechanism by which vitamin D might exert its action on sexual function appears to be through the regulation of endothelial function. Indeed, VDD correlates with several markers of endothelial function. The action of vitamin D on the endothelium would be exercised both indirectly through its intervention in inflammatory processes and through the production of oxygen free radicals, and directly through the regulation of vascular stiffness, the production of nitric oxide, and the regulation of vessel permeability. Furthermore, the ubiquitous distribution of the vitamin D receptor in the human body means that this hormone can also exert a beneficial effect on erectile function by interfering with those comorbidities significantly associated with ED, such as hypertension, diabetes mellitus, hypercholesterolemia, chronic kidney disease, and hypogonadism. In this review, we thoroughly and carefully presented the evidence and mechanisms that would appear to relate vitamin D levels to erectile function. Furthermore, we have summarized the meta-analytic evidence for and against this association to provide a true representation of this topic. Data published to date suggest that low levels of vitamin D could contribute to worsening erectile function through several mechanisms. Therefore, vitamin D levels should be measured in patients with ED and maintained at adequate levels by specific supplementation in case of deficiency. However, the low quality and heterogeneity of clinical trials evaluating the effects of vitamin D administration on erectile function and ED-associated comorbidities do not allow for a univocal conclusion, and indicate the need for further studies to analyze these aspects.

H19 Sperm Methylation in Male Infertility: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis summarize the difference in the methylation of the H19 gene in patients with abnormal versus normal conventional sperm parameters. It also evaluates the effects of age and sperm concentration on H19 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 H19 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 H19 methylation pattern should be evaluated among couples accessing assisted reproductive techniques (ART), in order to gain prognostic information on ART outcome and offspring health.

Once upon a Testis: The Tale of Cyclic Nucleotide Phosphodiesterase in Testicular Cancers.

Phosphodiesterases are key regulators that fine tune the intracellular levels of cyclic nucleotides, given their ability to hydrolyze cAMP and cGMP. They are critical regulators of cAMP/cGMP-mediated signaling pathways, modulating their downstream biological effects such as gene expression, cell proliferation, cell-cycle regulation but also inflammation and metabolic function. Recently, mutations in PDE genes have been identified and linked to human genetic diseases and PDEs have been demonstrated to play a potential role in predisposition to several tumors, especially in cAMP-sensitive tissues. This review summarizes the current knowledge and most relevant findings regarding the expression and regulation of PDE families in the testis focusing on PDEs role in testicular cancer development.