Journal of Assisted Reproduction and Genetics, 2020
Purpose To explore the possible influence of sperm quality, as assessed by prewash total sperm co... more Purpose To explore the possible influence of sperm quality, as assessed by prewash total sperm count (TSC), on cumulative success rates in assisted reproduction cycles. Methods Retrospective study carried out in private IVF centre. Seven hundred sixty-five couples undergoing complete ICSI cycles, i.e. whose all embryos were transferred or disposed of. Couples were characterised by male infertility and female age younger than 36 years. Couples with a combination of female and male infertility factors were excluded. The primary outcome measure was cumulative live birth rate. Secondary outcomes were cumulative pregnancy and miscarriage rates. No specific interventions were made. Results Higher TSC values have a positive impact on cumulative success rates in cycles characterised by few retrieved oocytes (1 to 5), while does not influence the outcome of cycles with a normal (6 to 10) or high (> 10) number of retrieved oocytes. Conclusions The study highlights the importance of sperm quality for the efficacy of assisted reproduction treatments. This influence may remain relatively cryptic in association with normal or high ovarian response, but emerge decisively in cases of reduced ovarian response, suggesting a relationship between ovarian response and oocyte ability to compensate for paternalderived deficiencies.
The phenotype of Klinefelter patients can be very different from one subject to another. In fact,... more The phenotype of Klinefelter patients can be very different from one subject to another. In fact, patients may have clear signs and symptoms related to chromosomal alteration or very little in some cases. Accordingly, it is common for the majority of them to remain undiagnosed or to have a late diagnosis during medical care for hypogonadism, couple infertility, or sexual problems. Therefore, each patient should be individually investigated to get a tailored treatment and follow-up. Moreover, the final judgement on the state of health of patients should not be based on the syndrome but on the individual condition. In the light of these considerations and because any subject with no chromosomal alteration may complain of the same problems, Klinefelter condition should be considered a variant of normalcy more than a disability.
и н ф е к ц и о н н о − в о с п а л и т е л ь н ы е з а б о л е в а н и я э к с п е р и м е н т а... more и н ф е к ц и о н н о − в о с п а л и т е л ь н ы е з а б о л е в а н и я э к с п е р и м е н т а л ь н а я и к л и н и ч е с к а я у р о л о г и я ¹ 3 2 0 2 0 w w w. e c u r o. r u
The aim of this review is to evaluate the complex interaction between HPV and human body, in orde... more The aim of this review is to evaluate the complex interaction between HPV and human body, in order to contextualize its role in the development of infective-related disease and neoplastic transformation. While the clinical value of vaccination on the field of gynecology has been widely investigated, the growing introduction of universal coverage (both males and females) leads to the need to extend investigations to adjunctive areas of interest. This is the rationale to extend and combine in a single review the main emerging areas where the HPV vaccination could induce an effective immunological response: HPV-related upper aerodigestive tract (UADT) pathologies, and HPV-related alterations of reproductive processes in males and females. There is no doubt that universal vaccination against HPV (9vHPV) is demonstrating its effectiveness in the prevention of most HPV-related conditions and worldwide prevalence data allow us to consider HPV vaccination from adolescence to late adulthood. We can conclude that: i) HPV infection is still very prevalent in sexually active population and may be associated to cervical, oropharyngeal, penile and anal cancers; ii) due to HPV vaccination and screening for cervical cancer, the incidence of cervical carcinoma is strongly decreased; iii) the rate of oropharyngeal cancer is growing worldwide and since 2010 it represents in males the most frequent HPV related cancer among U.S. population; iv) HPV semen infection, has been related to impaired sperm parameters, higher miscarriage rate and, in general, to couple infertility both by natural and assisted conception; v) recent efforts toward a universal vaccination against HPV have demonstrated its effectiveness in the prevention of most HPV-related conditions; vi) growing evidences suggest positive effects of adjuvant vaccination in patients with HPV related cancer and in HPV infected infertile couples.
Background: Risk factors established during adolescence affect health outcomes in adulthood, alth... more Background: Risk factors established during adolescence affect health outcomes in adulthood, although little is known about how adolescent health risk behaviours (HRBs) affect testicular development and reproductive health. Objectives: To assess prevalence of HRBs among last year high school students; to describe the most prevalent andrological disorders in this cohort; to explore HRBs associated with andrological disorders and investigate factors possibly associated with impaired testicular development in puberty. Materials and methods: The Amico-Andrologo Survey is a permanent nationwide surveillance programme conducted by the Italian Society of Andrology and Sexual Medicine and supported by the Ministry of Health. A nationally representative survey of finalyear male high school students was conducted using a validated structured interview (n = 10124) and medical examination (n = 3816). Results: Smoking (32.6%), drinking (80.6%) and use of illegal drugs (46.5%) are common in adolescence. 16.6% of subjects were overweight, 3.1% were underweight and 2.3% were obese. Among sexually active students (60.3%), unprotected sex was very common (48.3%). Only 11.6% had been treated for andrological disorders, despite an abnormal clinical examination in 34.6%. Bilateral testicular hypotrophy (14.0%), varicocoele (27.1%) and phimosis (7.1%) were the most prevalent disorders; 5.1% complained of premature ejaculation and 4.7% had an STI. Underweight and heavy alcohol or drug use were associated with testicular hypotrophy. HRBs emerged as significant predictors of testicular hypotrophy, explaining up to 9.6% of its variance. Limitations include risk of selection bias for voluntary physical examination and recall bias for the self-compiled questionnaire. Discussion: There is an emerging global adverse trend of HRBs in male high school students. A significant proportion of adolescent males with unsuspected andrological disorders engage in behaviours that could impair testicular development. Conclusion: Greater attention to the prevention of andrological health in adolescence is needed.
Testicular germ cell tumors (TGCTs) are prevalent in males of reproductive age. Among the availab... more Testicular germ cell tumors (TGCTs) are prevalent in males of reproductive age. Among the available therapeutic choices, pelvic radiotherapy (RT) and simple surveillance (SURV) are usually pursued. However, RT is considered to have lifethreatening effects on testicular functions. In this study we sought to clarify this issue by evaluating sperm parameters and sex hormones in 131 TGCTs RT-treated-patients at both baseline (T0) and 12 (T1) and 24 months (T2) of follow-up. An agematched group of 61 SURV patients served as control. Sperm parameters were comparable between SURV and RT at T0.
Background: Per-and poly-fluorinated alkyl substances (PFAS) are environmentpersitent emerging en... more Background: Per-and poly-fluorinated alkyl substances (PFAS) are environmentpersitent emerging endocrine disrupting chemicals raising health concerns worldwide. Exposure to PFAS has been associated with the imbalance of thyroid hormones. However, available studies addressing the cell mechanism underlying thyroid disrupting feature of legacy PFAS, such as perfluoro-octanoic acid (PFOA), perfluoro-octane-sulfonic acid (PFOS), and the new generation substitutes, such as C6O4, are still lacking. In this study the potential disrupting effect of PFOA, PFOS, and C6O4 on a murine thyroid cell model was assessed. Methods: A rat FRTL-5 cell line was used as the normal thyroid follicular cell model. Cell iodide-uptake, induced by thyroid stimulating hormone (TSH), was used to assess the functional impact of PFAS exposure on cell function. Tetrazolium salt-based cell viability assay and merocyanine 540-based cell staining were used to address the possible involvement of cell toxicity and membrane biophysical properties on altered cell function. The possible direct interaction of PFAS with TSH-receptor (TSH-R) was investigated by computer-based molecular docking and analysis of molecular dynamics. Evaluation of intracellular cAMP levels and gene expression analysis were used to validate the direct impairment of TSH-R-mediated downstream events upon PFAS exposure. Results: Different from PFOS or C6O4, exposure to PFOA at a concentration ≥ 10 ng/mL was associated with significant impairment of the iodide uptake upon TSH stimulation (respectively: basal 100.0 ± 19.0%, CTRL + TSH 188.9 ± 7.8%, PFOA 10 ng/mL + TSH 120.4 ± 20.9%, p= 0.030 vs CTRL + TSH; PFOA 100 ng/mL + TSH 115,6 ± 12,3% p= 0.017 vs CTRL + TSH). No impairment of cell viability or membrane stability was observed. Computational analysis showed a possible direct differential interaction of C6O4, PFOA, and PFOS on a same binding site of the extracellular domain of TSH-R. Finally, exposure to PFOA was associated with a significant reduction of downstream intracellular cAMP
Melanoma is a frequent neoplasm in young adult males in reproductive age, 10% of them degeneratin... more Melanoma is a frequent neoplasm in young adult males in reproductive age, 10% of them degenerating into regional and/or distant metastases (MM). The use of BRAF inhibitors (BRAFi) vemurafenib and dabrafenib is effective in MM patients harboring BRAF V600E/K/D mutations. Despite the increased life expectancy in MM patients
Background: Recent data suggest a potential role of testis in vitamin D activation, where Leydig ... more Background: Recent data suggest a potential role of testis in vitamin D activation, where Leydig cells could represent key players in this process since they express the highest amount of CYP2R1, a key enzyme involved in vitamin D 25 hydroxylation. Aim: To evaluate bone status in unilateral orchiectomy and to assess in vivo and in vitro LH-dependency of Vitamin D 25 hydroxylation. Subjects and methods: 125 normotestosteronemic patients with testicular cancer (TC), featured by unilateral orchiectomy and 41 age-matched healthy male controls were studied in the Center for Human Reproduction Pathology at the University of Padova. To evaluate LH-dependency of Vitamin D 25 hydroxylation in vitro, Leydig cell cultures were stimulated with hCG and assessed for CYP2R1 expression, whereas in vivo 10 hypogonadotropic hypogonadal (HH) patients were evaluated before and after treatment with gonadotropins for bone metabolism markers. Hormonal pattern and bone metabolism markers were measured in all subjects, whereas 105 patients and 41 controls underwent bone densitometry by DEXA. Results: In TC patients 25-hydroxyvitamin D levels were significantly lower compared to controls. Furthermore, 23.8% of patients with TC displayed low bone density (Z-score <-2 SD). None of the 41 control subjects showed any significant alteration of BMD. In vitro and in vivo studies revealed that CYP2R1 expression in Leydig cells appeared to be hCG dependent. Conclusion: Our data show an association between TC and alteration of the bone status, despite unvaried androgen and estrogen levels, suggesting the evaluation of bone status and possible vitamin D deficiency in TC survivors.
Reviews in endocrine and metabolic disorders, Jan 31, 2020
Growing evidence reports that obesity might play a role in erectile dysfunction (ED), but limited... more Growing evidence reports that obesity might play a role in erectile dysfunction (ED), but limited knowledge is available. We conducted a meta-analysis to estimate the prevalence of ED in overweight men and men with obesity. We performed a systematic review up to 01/04/2019 to investigate the associations between obesity and ED. Applying a random-effect model, we calculated the prevalence of ED, the odds ratio (OR) for the presence of ED by Body Mass Index (BMI) categories and the mean differences between ED and controls in BMI and Waist Circumference (WC). Among 3409 studies, we included 45 articles with 42,489 men (mean age = 55 years). Taking normal weight men as reference, the prevalence of ED was significantly higher in overweight (OR = 1.31; 95%CI: 1.13–1.51; I 2 = 72%) and in men with obesity (OR = 1.60; 95%CI: 1.29–1.98; I 2 = 79%). Adjusting our analyses for potential confounders, the results were confirmed in men with obesity (OR = 1.46; 95%CI: 1.24–1.72; I 2 = 72%). ED was associated with significant higher values of BMI (MD = 0.769; 95%CI: 0.565–0.973 Kg/m 2 ; I 2 = 78%) and WC (MD = 5.251 cm; 95%CI: 1.295–9.208; I 2 = 96%). Considering the high prevalence of ED among men with obesity, clinicians should screen for this clinical condition in this population. Findings from the present study suggest that reducing adiposity is a crucial approach in patients with ED who are affected by obesity.
Metabolomics proposes to unveil the molecular machinery involved in each specific disease by the ... more Metabolomics proposes to unveil the molecular machinery involved in each specific disease by the comprehensive analysis of low-molecular-weight metabolites in a biological sample. This narrative mini-review analyzes previous studies applying ultra-high-performance liquid chromatographyhigh-resolution mass spectrometry (HRMS)-based metabolomics to highlight different metabolic pathways involved in male hypogonadism and testosterone replacement therapy, both in the case of insulin-sensitive patients with primary hypogonadism and in the case of insulin-resistant patients with functional hypogonadism. In functional hypogonadism, metabolomics revealed that different biochemical pathways are affected. In detail, glycolysis is the most important biochemical process involved in these patients. Glucose metabolism is fueled by amino acid degradation, and gluconeogenesis is widely stimulated. Some important pathways, including glycerol, are compromised. Furthermore, mitochondrial electron transport is influenced, namely, by a decrease in ATP production. On the contrary, beta-oxidation of short-and medium-chain fatty acids does not represent an energy source in hypogonadal patients. Both lactate and acetyl-CoA are converted into ketone bodies, which increased immensely. However, carnosine and b-alanine are greatly reduced. These metabolic changes are associated with increased fatigue and mental confusion. After testosterone replacement therapy, a complete restoration is achieved for only a part of the metabolites. It is of note that only in patients with functional hypogonadism treated with testosterone are ketone bodies produced at high levels, so the symptoms sometimes reported by these patients after the beginning of the therapy (difficulty in concentrating, depressed mood, brain fog, and memory impairment) might represent a specific "keto flu-like" syndrome, related to the metabolic ketonic state.
Infertility is an important health problem affecting about 16% of couples worldwide and male infe... more Infertility is an important health problem affecting about 16% of couples worldwide and male infertility is responsible for about 50% of the cases. Among the causes, sexually transmittable infections (STI) are widely accepted by researchers as aetiological factors of male infertility and their incidence is growing. In detail, several reports documented the presence of HPV in semen from infertile patients. In these cases, HPV DNA was bound to the sperm surface and played a role in the infertility by affecting many sperm parameters. Despite a safe and highly effective vaccine is currently available to prevent HPV infection, there are still no effective treatments to completely clear the virus. However, recent studies highlighted that HPV vaccination can be an effective tool to counteract HPV seminal infection even in already infected patients. In fact, it seems able to reduce the viral time to clearance and the relapse of infection in males with persistence of HPV in semen. In this review, we aimed to explore, in a narrative way, currently available literature about HPV infection of male genital tract and the mechanisms by which HPV virions may alter sperm parameters and, therefore, male fertility, both natural and assisted. Moreover, we aimed to report and discuss the most recent evidences about the role of HPV vaccine administration as a therapeutic tool in males with persistent HPV seminal infection.
Environmental Science and Pollution Research, Nov 16, 2020
Male fertility and semen quality have declined over recent decades. Among other causes, exposure ... more Male fertility and semen quality have declined over recent decades. Among other causes, exposure to environmental and occupational pollution has been linked to adverse reproductive outcomes, but effects on male semen quality are still uncertain. Therefore, the aim of the present study was to conduct a systematic review and meta-analysis to assess current evidence regarding the impact of exposure to tobacco smoke and environmental and occupational pollution on sperm quality in humans. In the metaanalysis, 22 studies are included showing that environmental and occupational pollutants may affect sperm count, volume, concentration, motility, vitality and sperm DNA, and chromatin integrity. All included articles reported significant alterations in at least one of the outcomes studied in association with at least one of the pollutants studied. Considering that sperm quality can be considered a proxy for general health and that pollutants have a dramatic impact on climate change, it would be strongly recommended to better understand the role of pollutants on human, animal, and planetary health.
study question: Could sperm telomere length (STL) represent a novel parameter and biomarker of sp... more study question: Could sperm telomere length (STL) represent a novel parameter and biomarker of sperm quality? summary answer: STL is associated with standard semen quality parameters and, more importantly, it is significantly associated with levels of DNA fragmentation and sperm protamination. what is known already: Telomeres are fundamental for genome integrity. Recent studies have demonstrated that STL increases with age and men with oligozoospermia have shorter sperm telomeres than normozoospermic men. study design, size, duration: Cohort study conducted from September 2014 to June 2015 on 100 subjects with normal standard semen parameters. participants/materials, setting, methods: STL was measured indirectly by quantitative polymerase chain reaction using telomere/single-copy gene ratio, sperm DNA fragmentation by terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling assay and protamination by aniline blue staining. Data were analyzed for determining the relationships between STL, standard semen parameters and DNA fragmentation and protamination. main results and the role of chance: Among standard semen parameters, STL was positively associated with progressive motility (P ¼ 0.004) and vitality (P ¼ 0.007). STL was significantly and negatively associated with sperm DNA fragmentation (P ¼ 0.001) and significantly and positively associated with protamination (P ¼ 0.002). The role of chance was limited and the findings have biological relevance and a pathophysiological explanation. limitations, reasons for caution: For the present study, we deliberately selected only men with normozoospermia to better analyze whether STL might represent a biomarker of sperm quality beyond traditional sperm parameters. Additional studies in proven fertile men with normal sperm parameters are needed. wider implications of the findings: The measurement of STL is a simple and rapid method that offers further information about the quality of sperm. The results of this study demonstrate that STL could be considered as an additional sperm parameter and opens new perspectives in the evaluation of the infertile male. Additional studies will clarify the significance of this parameter also as a prognostic biomarker in assisted reproduction. study funding/competing interest(s): No external funding was either sought or obtained for this study. There are no conflicts of interest to be declared.
Sommario Un effetto collaterale che si associa alle terapie per il trattamento del tumore al test... more Sommario Un effetto collaterale che si associa alle terapie per il trattamento del tumore al testicolo è rappresentato dalla perdita della fertilità. Prima delle cure è importante affrontare l'argomento e informare il paziente sull'opportunità di preservare la fertilità. La possibilità offerta per ovviare a questo problema è quella di crioconservare gli spermatozoi. In seguito, se il potenziale di fertilità fosse idoneo, sarà possibile l'utilizzo del campione per un ciclo di Procreazione Medicalmente Assistita (PMA), rendendo possibile la paternità anche a pazienti che dopo la terapia adiuvante sono diventati sterili. Parole chiave Tumore al testicolo • Infertilità • Crioconservazione • Spermatozoi • PMA Introduzione La preservazione della fertilità è un tema molto rilevante e attuale per quanto concerne l'outcome del tumore al testicolo e, in generale, per tutte le neoplasie che richiedono trattamenti di chemioterapia e radioterapia. Infatti, molte di queste neoplasie si sviluppano e si manifestano nell'età fertile dell'uomo [1, 2]. L'intervento di orchiectomia e i trattamenti oncologici integrati sono sempre più efficaci ma anche gonadotossici e, pertanto, impongono già in fase di programmazione Proposto da Alberto Ferlin. Materiale elettronico supplementare La versione elettronica di questo articolo (
Journal of Assisted Reproduction and Genetics, 2020
Purpose To explore the possible influence of sperm quality, as assessed by prewash total sperm co... more Purpose To explore the possible influence of sperm quality, as assessed by prewash total sperm count (TSC), on cumulative success rates in assisted reproduction cycles. Methods Retrospective study carried out in private IVF centre. Seven hundred sixty-five couples undergoing complete ICSI cycles, i.e. whose all embryos were transferred or disposed of. Couples were characterised by male infertility and female age younger than 36 years. Couples with a combination of female and male infertility factors were excluded. The primary outcome measure was cumulative live birth rate. Secondary outcomes were cumulative pregnancy and miscarriage rates. No specific interventions were made. Results Higher TSC values have a positive impact on cumulative success rates in cycles characterised by few retrieved oocytes (1 to 5), while does not influence the outcome of cycles with a normal (6 to 10) or high (> 10) number of retrieved oocytes. Conclusions The study highlights the importance of sperm quality for the efficacy of assisted reproduction treatments. This influence may remain relatively cryptic in association with normal or high ovarian response, but emerge decisively in cases of reduced ovarian response, suggesting a relationship between ovarian response and oocyte ability to compensate for paternalderived deficiencies.
The phenotype of Klinefelter patients can be very different from one subject to another. In fact,... more The phenotype of Klinefelter patients can be very different from one subject to another. In fact, patients may have clear signs and symptoms related to chromosomal alteration or very little in some cases. Accordingly, it is common for the majority of them to remain undiagnosed or to have a late diagnosis during medical care for hypogonadism, couple infertility, or sexual problems. Therefore, each patient should be individually investigated to get a tailored treatment and follow-up. Moreover, the final judgement on the state of health of patients should not be based on the syndrome but on the individual condition. In the light of these considerations and because any subject with no chromosomal alteration may complain of the same problems, Klinefelter condition should be considered a variant of normalcy more than a disability.
и н ф е к ц и о н н о − в о с п а л и т е л ь н ы е з а б о л е в а н и я э к с п е р и м е н т а... more и н ф е к ц и о н н о − в о с п а л и т е л ь н ы е з а б о л е в а н и я э к с п е р и м е н т а л ь н а я и к л и н и ч е с к а я у р о л о г и я ¹ 3 2 0 2 0 w w w. e c u r o. r u
The aim of this review is to evaluate the complex interaction between HPV and human body, in orde... more The aim of this review is to evaluate the complex interaction between HPV and human body, in order to contextualize its role in the development of infective-related disease and neoplastic transformation. While the clinical value of vaccination on the field of gynecology has been widely investigated, the growing introduction of universal coverage (both males and females) leads to the need to extend investigations to adjunctive areas of interest. This is the rationale to extend and combine in a single review the main emerging areas where the HPV vaccination could induce an effective immunological response: HPV-related upper aerodigestive tract (UADT) pathologies, and HPV-related alterations of reproductive processes in males and females. There is no doubt that universal vaccination against HPV (9vHPV) is demonstrating its effectiveness in the prevention of most HPV-related conditions and worldwide prevalence data allow us to consider HPV vaccination from adolescence to late adulthood. We can conclude that: i) HPV infection is still very prevalent in sexually active population and may be associated to cervical, oropharyngeal, penile and anal cancers; ii) due to HPV vaccination and screening for cervical cancer, the incidence of cervical carcinoma is strongly decreased; iii) the rate of oropharyngeal cancer is growing worldwide and since 2010 it represents in males the most frequent HPV related cancer among U.S. population; iv) HPV semen infection, has been related to impaired sperm parameters, higher miscarriage rate and, in general, to couple infertility both by natural and assisted conception; v) recent efforts toward a universal vaccination against HPV have demonstrated its effectiveness in the prevention of most HPV-related conditions; vi) growing evidences suggest positive effects of adjuvant vaccination in patients with HPV related cancer and in HPV infected infertile couples.
Background: Risk factors established during adolescence affect health outcomes in adulthood, alth... more Background: Risk factors established during adolescence affect health outcomes in adulthood, although little is known about how adolescent health risk behaviours (HRBs) affect testicular development and reproductive health. Objectives: To assess prevalence of HRBs among last year high school students; to describe the most prevalent andrological disorders in this cohort; to explore HRBs associated with andrological disorders and investigate factors possibly associated with impaired testicular development in puberty. Materials and methods: The Amico-Andrologo Survey is a permanent nationwide surveillance programme conducted by the Italian Society of Andrology and Sexual Medicine and supported by the Ministry of Health. A nationally representative survey of finalyear male high school students was conducted using a validated structured interview (n = 10124) and medical examination (n = 3816). Results: Smoking (32.6%), drinking (80.6%) and use of illegal drugs (46.5%) are common in adolescence. 16.6% of subjects were overweight, 3.1% were underweight and 2.3% were obese. Among sexually active students (60.3%), unprotected sex was very common (48.3%). Only 11.6% had been treated for andrological disorders, despite an abnormal clinical examination in 34.6%. Bilateral testicular hypotrophy (14.0%), varicocoele (27.1%) and phimosis (7.1%) were the most prevalent disorders; 5.1% complained of premature ejaculation and 4.7% had an STI. Underweight and heavy alcohol or drug use were associated with testicular hypotrophy. HRBs emerged as significant predictors of testicular hypotrophy, explaining up to 9.6% of its variance. Limitations include risk of selection bias for voluntary physical examination and recall bias for the self-compiled questionnaire. Discussion: There is an emerging global adverse trend of HRBs in male high school students. A significant proportion of adolescent males with unsuspected andrological disorders engage in behaviours that could impair testicular development. Conclusion: Greater attention to the prevention of andrological health in adolescence is needed.
Testicular germ cell tumors (TGCTs) are prevalent in males of reproductive age. Among the availab... more Testicular germ cell tumors (TGCTs) are prevalent in males of reproductive age. Among the available therapeutic choices, pelvic radiotherapy (RT) and simple surveillance (SURV) are usually pursued. However, RT is considered to have lifethreatening effects on testicular functions. In this study we sought to clarify this issue by evaluating sperm parameters and sex hormones in 131 TGCTs RT-treated-patients at both baseline (T0) and 12 (T1) and 24 months (T2) of follow-up. An agematched group of 61 SURV patients served as control. Sperm parameters were comparable between SURV and RT at T0.
Background: Per-and poly-fluorinated alkyl substances (PFAS) are environmentpersitent emerging en... more Background: Per-and poly-fluorinated alkyl substances (PFAS) are environmentpersitent emerging endocrine disrupting chemicals raising health concerns worldwide. Exposure to PFAS has been associated with the imbalance of thyroid hormones. However, available studies addressing the cell mechanism underlying thyroid disrupting feature of legacy PFAS, such as perfluoro-octanoic acid (PFOA), perfluoro-octane-sulfonic acid (PFOS), and the new generation substitutes, such as C6O4, are still lacking. In this study the potential disrupting effect of PFOA, PFOS, and C6O4 on a murine thyroid cell model was assessed. Methods: A rat FRTL-5 cell line was used as the normal thyroid follicular cell model. Cell iodide-uptake, induced by thyroid stimulating hormone (TSH), was used to assess the functional impact of PFAS exposure on cell function. Tetrazolium salt-based cell viability assay and merocyanine 540-based cell staining were used to address the possible involvement of cell toxicity and membrane biophysical properties on altered cell function. The possible direct interaction of PFAS with TSH-receptor (TSH-R) was investigated by computer-based molecular docking and analysis of molecular dynamics. Evaluation of intracellular cAMP levels and gene expression analysis were used to validate the direct impairment of TSH-R-mediated downstream events upon PFAS exposure. Results: Different from PFOS or C6O4, exposure to PFOA at a concentration ≥ 10 ng/mL was associated with significant impairment of the iodide uptake upon TSH stimulation (respectively: basal 100.0 ± 19.0%, CTRL + TSH 188.9 ± 7.8%, PFOA 10 ng/mL + TSH 120.4 ± 20.9%, p= 0.030 vs CTRL + TSH; PFOA 100 ng/mL + TSH 115,6 ± 12,3% p= 0.017 vs CTRL + TSH). No impairment of cell viability or membrane stability was observed. Computational analysis showed a possible direct differential interaction of C6O4, PFOA, and PFOS on a same binding site of the extracellular domain of TSH-R. Finally, exposure to PFOA was associated with a significant reduction of downstream intracellular cAMP
Melanoma is a frequent neoplasm in young adult males in reproductive age, 10% of them degeneratin... more Melanoma is a frequent neoplasm in young adult males in reproductive age, 10% of them degenerating into regional and/or distant metastases (MM). The use of BRAF inhibitors (BRAFi) vemurafenib and dabrafenib is effective in MM patients harboring BRAF V600E/K/D mutations. Despite the increased life expectancy in MM patients
Background: Recent data suggest a potential role of testis in vitamin D activation, where Leydig ... more Background: Recent data suggest a potential role of testis in vitamin D activation, where Leydig cells could represent key players in this process since they express the highest amount of CYP2R1, a key enzyme involved in vitamin D 25 hydroxylation. Aim: To evaluate bone status in unilateral orchiectomy and to assess in vivo and in vitro LH-dependency of Vitamin D 25 hydroxylation. Subjects and methods: 125 normotestosteronemic patients with testicular cancer (TC), featured by unilateral orchiectomy and 41 age-matched healthy male controls were studied in the Center for Human Reproduction Pathology at the University of Padova. To evaluate LH-dependency of Vitamin D 25 hydroxylation in vitro, Leydig cell cultures were stimulated with hCG and assessed for CYP2R1 expression, whereas in vivo 10 hypogonadotropic hypogonadal (HH) patients were evaluated before and after treatment with gonadotropins for bone metabolism markers. Hormonal pattern and bone metabolism markers were measured in all subjects, whereas 105 patients and 41 controls underwent bone densitometry by DEXA. Results: In TC patients 25-hydroxyvitamin D levels were significantly lower compared to controls. Furthermore, 23.8% of patients with TC displayed low bone density (Z-score <-2 SD). None of the 41 control subjects showed any significant alteration of BMD. In vitro and in vivo studies revealed that CYP2R1 expression in Leydig cells appeared to be hCG dependent. Conclusion: Our data show an association between TC and alteration of the bone status, despite unvaried androgen and estrogen levels, suggesting the evaluation of bone status and possible vitamin D deficiency in TC survivors.
Reviews in endocrine and metabolic disorders, Jan 31, 2020
Growing evidence reports that obesity might play a role in erectile dysfunction (ED), but limited... more Growing evidence reports that obesity might play a role in erectile dysfunction (ED), but limited knowledge is available. We conducted a meta-analysis to estimate the prevalence of ED in overweight men and men with obesity. We performed a systematic review up to 01/04/2019 to investigate the associations between obesity and ED. Applying a random-effect model, we calculated the prevalence of ED, the odds ratio (OR) for the presence of ED by Body Mass Index (BMI) categories and the mean differences between ED and controls in BMI and Waist Circumference (WC). Among 3409 studies, we included 45 articles with 42,489 men (mean age = 55 years). Taking normal weight men as reference, the prevalence of ED was significantly higher in overweight (OR = 1.31; 95%CI: 1.13–1.51; I 2 = 72%) and in men with obesity (OR = 1.60; 95%CI: 1.29–1.98; I 2 = 79%). Adjusting our analyses for potential confounders, the results were confirmed in men with obesity (OR = 1.46; 95%CI: 1.24–1.72; I 2 = 72%). ED was associated with significant higher values of BMI (MD = 0.769; 95%CI: 0.565–0.973 Kg/m 2 ; I 2 = 78%) and WC (MD = 5.251 cm; 95%CI: 1.295–9.208; I 2 = 96%). Considering the high prevalence of ED among men with obesity, clinicians should screen for this clinical condition in this population. Findings from the present study suggest that reducing adiposity is a crucial approach in patients with ED who are affected by obesity.
Metabolomics proposes to unveil the molecular machinery involved in each specific disease by the ... more Metabolomics proposes to unveil the molecular machinery involved in each specific disease by the comprehensive analysis of low-molecular-weight metabolites in a biological sample. This narrative mini-review analyzes previous studies applying ultra-high-performance liquid chromatographyhigh-resolution mass spectrometry (HRMS)-based metabolomics to highlight different metabolic pathways involved in male hypogonadism and testosterone replacement therapy, both in the case of insulin-sensitive patients with primary hypogonadism and in the case of insulin-resistant patients with functional hypogonadism. In functional hypogonadism, metabolomics revealed that different biochemical pathways are affected. In detail, glycolysis is the most important biochemical process involved in these patients. Glucose metabolism is fueled by amino acid degradation, and gluconeogenesis is widely stimulated. Some important pathways, including glycerol, are compromised. Furthermore, mitochondrial electron transport is influenced, namely, by a decrease in ATP production. On the contrary, beta-oxidation of short-and medium-chain fatty acids does not represent an energy source in hypogonadal patients. Both lactate and acetyl-CoA are converted into ketone bodies, which increased immensely. However, carnosine and b-alanine are greatly reduced. These metabolic changes are associated with increased fatigue and mental confusion. After testosterone replacement therapy, a complete restoration is achieved for only a part of the metabolites. It is of note that only in patients with functional hypogonadism treated with testosterone are ketone bodies produced at high levels, so the symptoms sometimes reported by these patients after the beginning of the therapy (difficulty in concentrating, depressed mood, brain fog, and memory impairment) might represent a specific "keto flu-like" syndrome, related to the metabolic ketonic state.
Infertility is an important health problem affecting about 16% of couples worldwide and male infe... more Infertility is an important health problem affecting about 16% of couples worldwide and male infertility is responsible for about 50% of the cases. Among the causes, sexually transmittable infections (STI) are widely accepted by researchers as aetiological factors of male infertility and their incidence is growing. In detail, several reports documented the presence of HPV in semen from infertile patients. In these cases, HPV DNA was bound to the sperm surface and played a role in the infertility by affecting many sperm parameters. Despite a safe and highly effective vaccine is currently available to prevent HPV infection, there are still no effective treatments to completely clear the virus. However, recent studies highlighted that HPV vaccination can be an effective tool to counteract HPV seminal infection even in already infected patients. In fact, it seems able to reduce the viral time to clearance and the relapse of infection in males with persistence of HPV in semen. In this review, we aimed to explore, in a narrative way, currently available literature about HPV infection of male genital tract and the mechanisms by which HPV virions may alter sperm parameters and, therefore, male fertility, both natural and assisted. Moreover, we aimed to report and discuss the most recent evidences about the role of HPV vaccine administration as a therapeutic tool in males with persistent HPV seminal infection.
Environmental Science and Pollution Research, Nov 16, 2020
Male fertility and semen quality have declined over recent decades. Among other causes, exposure ... more Male fertility and semen quality have declined over recent decades. Among other causes, exposure to environmental and occupational pollution has been linked to adverse reproductive outcomes, but effects on male semen quality are still uncertain. Therefore, the aim of the present study was to conduct a systematic review and meta-analysis to assess current evidence regarding the impact of exposure to tobacco smoke and environmental and occupational pollution on sperm quality in humans. In the metaanalysis, 22 studies are included showing that environmental and occupational pollutants may affect sperm count, volume, concentration, motility, vitality and sperm DNA, and chromatin integrity. All included articles reported significant alterations in at least one of the outcomes studied in association with at least one of the pollutants studied. Considering that sperm quality can be considered a proxy for general health and that pollutants have a dramatic impact on climate change, it would be strongly recommended to better understand the role of pollutants on human, animal, and planetary health.
study question: Could sperm telomere length (STL) represent a novel parameter and biomarker of sp... more study question: Could sperm telomere length (STL) represent a novel parameter and biomarker of sperm quality? summary answer: STL is associated with standard semen quality parameters and, more importantly, it is significantly associated with levels of DNA fragmentation and sperm protamination. what is known already: Telomeres are fundamental for genome integrity. Recent studies have demonstrated that STL increases with age and men with oligozoospermia have shorter sperm telomeres than normozoospermic men. study design, size, duration: Cohort study conducted from September 2014 to June 2015 on 100 subjects with normal standard semen parameters. participants/materials, setting, methods: STL was measured indirectly by quantitative polymerase chain reaction using telomere/single-copy gene ratio, sperm DNA fragmentation by terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling assay and protamination by aniline blue staining. Data were analyzed for determining the relationships between STL, standard semen parameters and DNA fragmentation and protamination. main results and the role of chance: Among standard semen parameters, STL was positively associated with progressive motility (P ¼ 0.004) and vitality (P ¼ 0.007). STL was significantly and negatively associated with sperm DNA fragmentation (P ¼ 0.001) and significantly and positively associated with protamination (P ¼ 0.002). The role of chance was limited and the findings have biological relevance and a pathophysiological explanation. limitations, reasons for caution: For the present study, we deliberately selected only men with normozoospermia to better analyze whether STL might represent a biomarker of sperm quality beyond traditional sperm parameters. Additional studies in proven fertile men with normal sperm parameters are needed. wider implications of the findings: The measurement of STL is a simple and rapid method that offers further information about the quality of sperm. The results of this study demonstrate that STL could be considered as an additional sperm parameter and opens new perspectives in the evaluation of the infertile male. Additional studies will clarify the significance of this parameter also as a prognostic biomarker in assisted reproduction. study funding/competing interest(s): No external funding was either sought or obtained for this study. There are no conflicts of interest to be declared.
Sommario Un effetto collaterale che si associa alle terapie per il trattamento del tumore al test... more Sommario Un effetto collaterale che si associa alle terapie per il trattamento del tumore al testicolo è rappresentato dalla perdita della fertilità. Prima delle cure è importante affrontare l'argomento e informare il paziente sull'opportunità di preservare la fertilità. La possibilità offerta per ovviare a questo problema è quella di crioconservare gli spermatozoi. In seguito, se il potenziale di fertilità fosse idoneo, sarà possibile l'utilizzo del campione per un ciclo di Procreazione Medicalmente Assistita (PMA), rendendo possibile la paternità anche a pazienti che dopo la terapia adiuvante sono diventati sterili. Parole chiave Tumore al testicolo • Infertilità • Crioconservazione • Spermatozoi • PMA Introduzione La preservazione della fertilità è un tema molto rilevante e attuale per quanto concerne l'outcome del tumore al testicolo e, in generale, per tutte le neoplasie che richiedono trattamenti di chemioterapia e radioterapia. Infatti, molte di queste neoplasie si sviluppano e si manifestano nell'età fertile dell'uomo [1, 2]. L'intervento di orchiectomia e i trattamenti oncologici integrati sono sempre più efficaci ma anche gonadotossici e, pertanto, impongono già in fase di programmazione Proposto da Alberto Ferlin. Materiale elettronico supplementare La versione elettronica di questo articolo (
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