"Management of andrological disorders from childhood and adolescence to transition age: guidelines from the Italian Society of Andrology and Sexual Medicine (SIAMS) in collaboration with the Italian Society for Pediatric Endocrinology and Diabetology (SIEDP)-Part-1".

PURPOSE: Andrological pathologies in the adulthood are often the results of conditions that originate during childhood and adolescence and sometimes even during gestation and neonatal period. Unfortunately, the reports in the literature concerning pediatric andrological diseases are scares and mainly concerning single issues. Furthermore, no shared position statement are so far available. METHODS: The Italian Society of Andrology and Sexual Medicine (SIAMS) commissioned an expert task force involving the Italian Society of Pediatric Endocrinology and Diabetology (SIEDP) to provide an updated guideline on the diagnosis and management of andrological disorders from childhood and adolescence to transition age. Derived recommendations were based on the grading of recommendations, assessment, development, and evaluation (GRADE) system. RESULTS: A literature search of articles in English for the term "varicoceles", "gynecomastia", "fertility preservation", "macroorchidism", "precocious puberty" and "pubertal delay" has been performed. Three major aspects for each considered disorder were assessed including diagnosis, clinical management, and treatment. Recommendations and suggestions have been provided for each of the mentioned andrological disorders. CONCLUSIONS: These are the first guidelines based on a multidisciplinary approach that involves important societies related to the field of andrological medicine from pediatric to transition and adult ages. This fruitful discussion allowed for a general agreement on several recommendations and suggestions to be reached, which can support all stakeholders in improving andrological and general health of the transitional age.

Getting old in the desired gender: a systematic review on aging diseases in transgender people.

INTRODUCTION: The growing demographic presence of the transgender (TGD) population has sparked an increase in clinical investigations focusing on the impacts of gender-affirming hormone therapy (GAHT) in adults with gender dysphoria. Despite this surge in studies, there remains a significant gap in the literature regarding the health status of older TGD individuals. This review aims to assess prevalent pathological conditions within the TGD population, specifically concentrating on aging-related diseases investigated to date. METHODS: A systematic search across Embase Ovid, Scopus, PubMed, Cochrane Library, and Web of Science databases was conducted to identify articles reporting on the aging process in TGD individuals. Methodological quality was evaluated using Newcastle-Ottawa Scale (NOS) scores. RESULTS: Initial database searches yielded 12,688 studies, which were refined to 18 through elimination of duplicates and title/abstract review. Following a comprehensive appraisal, nine studies were included in the systematic review. These articles, published between 2017 and 2023, involved a total of 5403 participants. The evidence indicates a noteworthy percentage of the TGD population being at risk for cardiovascular diseases, experiencing depression or disability, and demonstrating hesitancy toward major recommended screening programs. CONCLUSIONS: Limited studies on older TGD individuals highlight not only an organic risk of chronic diseases but also a cognitive/psychiatric risk that should not be underestimated. Further research is imperative to deepen our understanding of the pathophysiological mechanisms involved in the health challenges faced by older TGD individuals.

Communication of the diagnosis to Klinefelter subjects: an observational study on a key moment of the patient's life.

PURPOSE: Klinefelter syndrome (KS) is the most prevalent sex chromosome disorder among males. The communication of the KS diagnosis holds significant implications for the diagnosis's acceptance. Recently, the increased use of prenatal diagnostic procedures has raised the question of whether, when, and by whom information, once provided to parents, should be communicated to their children/adolescents. Currently, there is limited information on this topic. This study aims to investigate the most suitable timing, content, and healthcare professionals (HCPs) according to KS patients' suggestions for conveying the diagnosis, analyzing the impact of communicating the KS diagnosis on patients and their reception of the communication in real-life situations. Furthermore, research entails a comparison of the actual communication and the patients' preferred mode of communication. METHODS: Self-reported interview data was collected from 196 adults diagnosed with KS. The interview was structured, consisting of 32 multiple-choice questions covering various areas related to diagnosis communication. RESULTS: Most patients with Klinefelter syndrome reported that earlier communication would have been beneficial. Communication before the age of 18 and by parents increased the likelihood of overcoming negative consequences and relying on psychological support. CONCLUSION: To mitigate the adverse effects of poorly timed and inadequately delivered communication, typically by a single person, it is advisable that such communication be carried out at the onset of adolescence by an interdisciplinary team of HCPs (including psychologists, geneticists, endocrinologists) and parents. The information provided should not solely concentrate on hormonal and fertility aspects, but also consider other factors such as psychological variables.

HPV-related diseases in male patients: an underestimated conundrum.

PURPOSE: Human papillomavirus (HPV) infection is the most common sexually transmitted disease, in males and females worldwide. While the role of HPV in female diseases is well known and largely studied, males have negligibly been included in these programs, also because the proportion of women suffering and dying from HPV-related diseases is much larger than men. The aim of this review is to focus on HPV-related diseases in male patients. METHODS: We performed a literature analysis on the electronic database PubMed. We considered randomized trials, observational and retrospective studies, original articles having as topic the relationship between HPV male infection and the following items: oral, anal penile cancers, warts, condylomas, male infertility, altered sperm parameters, anti-sperm antibodies (ASA). We also included experimental in vitro studies focused on the effects of HPV infection on oocyte fertilization, blastocyst development, and trophoblastic cell invasiveness. In addition, studies describing the adjuvant administration of the HPV vaccination as a possible strategy to promote HPV clearance from semen in infected males were included. RESULTS: Regarding head and neck HPV-related diseases, the most important non-neoplastic disease is recurrent respiratory papillomatosis (RRP). Regarding neoplastic diseases, the proportion of head and neck cancers attributable to HPV has increased dramatically worldwide. In addition, nowadays, it is thought that half of head and neck squamous cell carcinomas (HNSCCs) cases in the United States are caused by infection with high-risk HPV. HPV is noteworthy in andrological practice too. It was described as having a high HPV prevalence, ranging between 50 and 70%, in male penile shaft, glans penis/coronal sulcus, semen as well as in scrotal, perianal, and anal regions. Moreover, in male patients, HPV infection has been associated, among other diseases, with penile cancers. HPV semen infection has been reported in about 10% in men from the general population and about 16% in men with unexplained infertility, although these data seem widely underestimated according to clinical experience. In particular, HPV semen infection seems to be most related to asthenozoospermia and to anti-sperm antibodies (ASAs). CONCLUSIONS: HPV infection represents a health problem with a detrimental social and public impact. Despite this evidence, little has been done to date to widely promote vaccination among young males.

Bone health and body composition in transgender adults before gender-affirming hormonal therapy: data from the COMET study.

PURPOSE: Preliminary data suggested that bone mineral density (BMD) in transgender adults before initiating gender-affirming hormone therapy (GAHT) is lower when compared to cisgender controls. In this study, we analyzed bone metabolism in a sample of transgender adults before GAHT, and its possible correlation with biochemical profile, body composition and lifestyle habits (i.e., tobacco smoke and physical activity). METHODS: Medical data, smoking habits, phospho-calcic and hormonal blood tests and densitometric parameters were collected in a sample of 125 transgender adults, 78 Assigned Females At Birth (AFAB) and 47 Assigned Males At Birth (AMAB) before GAHT initiation and 146 cisgender controls (57 females and 89 males) matched by sex assigned at birth and age. 55 transgender and 46 cisgender controls also underwent a complete body composition evaluation and assessment of physical activity using the International Physical Activity Questionnaire (IPAQ). RESULTS: 14.3% of transgender and 6.2% of cisgender sample, respectively, had z-score values < -2 (p = 0.04). We observed only lower vitamin D values in transgender sample regarding biochemical/hormonal profile. AFAB transgender people had more total fat mass, while AMAB transgender individuals had reduced total lean mass as compared to cisgender people (53.94 ± 7.74 vs 58.38 ± 6.91, p < 0.05). AFAB transgender adults were more likely to be active smokers and tend to spend more time indoor. Fat Mass Index (FMI) was correlated with lumbar and femur BMD both in transgender individuals, while no correlations were found between lean mass parameters and BMD in AMAB transgender people. CONCLUSIONS: Body composition and lifestyle factors could contribute to low BMD in transgender adults before GAHT.

First baseline data of the Klinefelter ItaliaN Group (KING) cohort: clinical features of adult with Klinefelter syndrome in Italy.

BACKGROUND: Klinefelter syndrome (KS) is frustratingly under-diagnosed. KS have a broad spectrum of clinical features, making it difficult to identify.  OBJECTIVE: We describe KS clinical presentation in a large Italian cohort. DESIGN: This is the first observational cohort study within a national network, the Klinefelter ItaliaN Group (KING). Primary outcomes were to describe the basic clinical features and the actual phenotype of KS in Italy. Secondary outcomes were to determine age at diagnosis and geographical distribution. METHODS: We performed a basic phenotyping and evaluation of the hormonal values of 609 adult KS patients. RESULTS: Mean age at diagnosis was 37.4 ± 13.4 years. The overall mean testicular size was 3 ml, and 2.5 ml in both testes in untreated KS group. BMI was 26.6 ± 5.8 kg/m2, and 25.5% of KS had metabolic syndrome (MetS). LH and FSH were increased, and mean total testosterone were 350 ± 9.1 ng/dl. A descriptive analysis showed that 329 KS patients were evaluated in Northern Italy, 76 in Central and 204 in Southern Italy. Analysis of variance demonstrated significant statistical differences (p < 0001) between the age at diagnosis of the three geographical groups. Compared with the expected number among male patients matched for age in Italy, only 16% of KS patients received a diagnosis. CONCLUSIONS: These data are the results of the only national database available that collects the clinical and hormonal data of the KS patients, currently referred at the KING centers. In Italy the typical KS patient is overweight, with small testes, and elevated LH and FSH. Only 25.5% of them are diagnosed with MetS. Early detection and timely treatment are mandatory.

Testosterone treatment in male patients with Klinefelter syndrome: a systematic review and meta-analysis.

PURPOSE: Low testosterone (T) in Klinefelter's syndrome (KS) can contribute to typical features of the syndrome such as reduced bone mineral density, obesity, metabolic disturbances and increased cardiovascular risk. The aim of the present study is to review and meta-analyze all available information regarding possible differences in metabolic and bone homeostasis profile between T treated (TRT) or untreated KS and age-matched controls. METHODS: We conducted a random effect meta-analysis considering all the available data from observational or randomized controlled studies comparing TRT-treated and untreated KS and age-matched controls. Data were derived from an extensive MEDLINE, Embase, and Cochrane search. RESULTS: Out of 799 retrieved articles, 21 observational and 22 interventional studies were included in the study. Retrieved trials included 1144 KS subjects and 1284 healthy controls. Not-treated KS patients showed worse metabolic profiles (including higher fasting glycemia and HOMA index as well as reduced HDL-cholesterol and higher LDL-cholesterol) and body composition (higher body mass index and waist circumference) and reduced bone mineral density (BMD) when compared to age-matched controls. TRT in hypogonadal KS subjects was able to improve body composition and BMD at spinal levels but it was ineffective in ameliorating lipid and glycemic profile. Accordingly, TRT-treated KS subjects still present worse metabolic parameters when compared to age-matched controls. CONCLUSION: TRT outcomes observed in KS regarding BMD, body composition and glyco-metabolic control, are similar to those observed in male with hypogonadism not related to KS. Moreover, body composition and BMD are better in treated than untreated hypogonadal KS. Larger and longer randomized placebo-controlled trials are advisable to better confirm the present data, mainly derived from observational studies.

Perfluoro-octanoic acid impairs sperm motility through the alteration of plasma membrane.

CONTEXT: Perfluoroalkyl-substances (PFAS) are chemical additives considered harmful for humans. We recently showed that accumulation of perfluoro-octanoic acid (PFOA) in human semen of exposed subjects was associated with altered motility parameters of sperm cells, suggesting direct toxicity. OBJECTIVES: To determine whether direct exposure of human spermatozoa to PFOA was associated to impairment of cell function. PATIENTS AND METHODS: Spermatozoa isolated from semen samples of ten normozoospermic healthy donors were exposed up to 2 h to PFOA, at concentrations from 0.1 to 10 ng/mL. Viability and motility parameters were evaluated by Sperm Class Analyser. Cell respiratory function was assessed by both mitochondrial probe JC-1 and respiratory control ratio (RCR) determination. Sperm accumulation of PFOA was quantified by liquid chromatography-mass spectrometry. Expression of organic ion-transporters OATP1 and SLCO1B2 was assessed by immunofluorescence and respective role in PFOA accumulation was evaluated by either blockade with probenecid or membrane scavenging through ß-cyclodextrin (ß-CD). Plasma membrane fluidity and electrochemical potential (ΔΨp) were evaluated, respectively, with Merocyanine-540 and Di-3-ANEPPDHQ fluorescent probes. RESULTS: Compared to untreated controls, a threefold increase of the percentage of non-motile sperms was observed after 2 h of exposure to PFOA regardless of the concentration of PFOA, whilst RCR was significantly reduced. Only scavenging with ß-CD was effective in reducing PFOA accumulation, suggesting membrane involvement. Altered membrane fluidity, reduced ΔΨp and sperm motility loss associated with exposure to PFOA were reverted by ß-CD treatment. CONCLUSION: PFOA alters human sperm motility through plasma-membrane disruption, an effect recovered by incubation with ß-CD.

Risk behaviours and alcohol in adolescence are negatively associated with testicular volume: results from the Amico-Andrologo survey.

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 final-year 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.

Penile doppler ultrasound predicts cardiovascular events in men with erectile dysfunction.

BACKGROUND: Traditional risk factors used to assess cardiovascular risk miss a significant population who are indeed at risk for future cardiac events. Erectile dysfunction (ED) is an emerging marker for future cardiovascular disease (CVD) and major adverse cardiovascular events (MACE), especially in young and middle-aged men with vasculogenic ED. Cavernous arteries morphological alterations at penile colour doppler ultrasound (P-CDU) are used to find a vasculogenic ED. OBJECTIVES: We investigated the possible relationship between cavernous arteries morphological alterations at P-CDU assessment and future MACE. MATERIALS AND METHODS: We conducted a retrospective cohort study involving 300 ED patients, aged 35-65 years (mean age 54.1 ± 7.1), with a follow-up period of 10 years. Patients underwent vascular evaluation including P-CDU, colour doppler ultrasound of the carotid and lower limbs arteries. At baseline data for glucose metabolism, lipid profile, hypertension and hormonal status were collected. During the follow-up period, the occurrence of MACE was evaluated. RESULTS: We found a strong association between cavernous arteries morphological alterations and CVD with a threefold increased risk of future MACE in comparison to patients with healthy cavernous arteries (RR 3.2, 95% CI 1.17-8.78). This association remained statistically significant after adjustment for CV risk factors (age, glycaemia, total cholesterol, hypertension and smoke). CONCLUSIONS: Morphological alterations of cavernous arteries are independently associated with an increased risk of future MACE. These data contribute to the formulation of the hypothesis that cavernous artery pathology at P-CDU is related to MACE.

Anogenital distance is associated with genital measures and seminal parameters but not anthropometrics in a large cohort of young adult men.

STUDY QUESTION: Is the anogenital distance (AGD) correlated to anthropometric, genital and sperm parameters in young adult men? SUMMARY ANSWER: We observed that reduced AGD is strongly associated with altered semen parameters and reduced testicular volume. WHAT IS KNOWN ALREADY: Abnormalities in the foetal development of the testis have been suggested as causative of common male reproductive disorders, such as cryptorchidism, hypospadias, reduced semen quality and testicular germ cell tumour, collectively defined as 'testicular dysgenesis syndrome'. In human epidemiological studies, alterations in AGD have been frequently associated with clinically relevant outcomes of reproductive health, suggesting AGD as a marker of foetal testicular development. STUDY DESIGN, SIZE, DURATION: This study was performed within the annual screening protocol to evaluate male reproductive health in the high schools of Padua and surroundings (Veneto Region, the North-East of Italy). Here we report the findings of 794 subjects who completed the study protocol between October 2016 and May 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: We evaluated 794 students aged 18-19 years recording the following parameters: height, weight, BMI, waist circumference, arm span, pubis-to-floor and crown-to-pubis length, penile length and circumference, testicular volumes, semen parameters and AGD (measured from the posterior base of the scrotum to the centre of the anus). MAIN RESULTS AND THE ROLE OF CHANCE: Of the subjects, 49% had an abnormal arm span-height difference (>3 cm) and 63.4% had an altered ratio of crown-to-pubis/pubis-to-floor length (≤0.92). The rate of subjects with reduced testicular volume was 23%. Median sperm concentration was 51.0× 106/ml and total sperm count was 122.5 × 106. AGD showed a direct positive relation with testicular volume and penile length and circumference (R = 0.265, 0.176 and 0.095, respectively, all P < 0.05). No significant relation was observed between AGD and anthropometric parameters. Sperm concentration, total sperm count, progressive motility and normal morphology showed a significant and positive correlation with AGD (R = 0.205, 0.210, 0.216 and 0.117, respectively, all P < 0.05). LIMITATIONS, REASONS FOR CAUTION: Our cohort of young adults is not representative of the general population. Hormonal evaluation was missing. WIDER IMPLICATIONS OF THE FINDINGS: Our findings show that AGD is associated with testicular volumes, penile measures and seminal parameters in young adult men. Because AGD is hormonally determined during foetal life, the reported high incidence of reduced semen quality and reduced testicular volume could be related to a reduced androgenic exposure in utero. AGD could represent a simple and useful method to evaluate testicular and penile development in adult men. STUDY FUNDING/COMPETING INTEREST(S): The authors have no potential conflict of interest to declare. No external funding was obtained for this study. TRIAL REGISTRATION NUMBER: N/A.

Impaired sperm function in infertile men relies on the membrane sterol pattern.

Membrane cholesterol removal appears a key step for the gain of fertility potential during sperm maturation. However, the membrane sterol pattern in sperm cells from infertile patients, with impaired sperm parameters, has been poorly investigated. To elucidate a causative link between sperm membrane composition in male fertility, here we have investigated the levels of cholesterol and its oxidized derivatives 7ß-hydroxycholesterol and 7-keto-cholesterol in sixteen infertile patients with oligo-asthenozoospermia and 16 normozoospermic (N) fertile subjects. Furthermore, ten of 16 N fertile subjects agreed to receive a defined testicular thermal challenge by adhering to a programme of sauna sessions for 1 month. Semen samples were obtained from each of the participants, and sperm parameters were assessed according to the World Health Organization criteria. Sperm levels of cholesterol, 7ß-hydroxycholesterol and 7-keto-cholesterol were quantified by ultra-pressure liquid chromatography mass spectrometry. The results showed that oligo-asthenozoospermia patients had a huge amount of cholesterol content compared with fertile subjects (12.40 ± 6.05 µg/106 cells vs. 0.45 ± 0.28 µg/106 cells, p < 0.001, N and oligo-asthenozoospermia, respectively). Also, oxidized derivatives were significantly higher in oligo-asthenozoospermia patients (7ß-hydroxycholesterol: 1.96 ± 1.03 ng/106 cells vs. 0.075 ± 0.05 ng/106 cells, p < 0.001 and 7-keto-cholesterol: 1.11 ± 0.72 ng/106 cells vs. 0.005 ± 0.003 ng/106 cells, p < 0.001). Moreover, sauna exposure, in parallel with a progressive worsening of sperm motility parameters, was associated with a reversible increase in sperm cholesterol after the third and fourth week of treatment, whilst 7ß-hydroxycholesterol and 7-keto-cholesterol levels showed an earlier enhancement starting from the second week. Our data show for the first time in humans a strong difference in the cholesterol and its oxidized derivatives of infertile and fertile subjects. These findings suggest a strict biochemical link relating testis function, sperm membrane status and male fertility potential.

Prednisone treatment in infertile patients with oligozoospermia and accessory gland inflammatory alterations.

The association between inflammation of the male reproductive system and oligozoospermia has been frequently reported in the clinical work-up of male infertility. To improve sperm parameters in infertile patients with genital inflammation, many phytochemical and nutraceutical drugs are currently being used. However, their use is still empirical and no conclusive data have been provided about their efficacy. The treatment with steroid anti-inflammatory drugs might be useful in reducing inflammation and improving sperm parameters, thus increasing the fertility outcome. The aim of this study was to evaluate if glucocorticoid treatment improves seminal parameters in infertile oligozoospermic patients presenting signs of accessory gland inflammation at genital ultrasound. A total of 90 infertile patients were enrolled in the study. They presented normal testicular volume, normal FSH plasma levels, the presence of various degrees of oligozoospermia, associated with scrotal and trans-rectal ultrasound signs indicative of accessory gland inflammation, but negative microbiological analysis on semen and/or prostatic secretions. Patients were randomly allocated into three groups of treatment, receiving, respectively, 5, 12.5, and 25 mg daily oral Prednisone for one month. Seminal parameters were evaluated at admission and after treatment. In patients undergoing Prednisone treatment at a daily dose of 5 mg we observed a significant increase in total sperm count. At a daily dose of 12.5 mg, Prednisone treatment improved sperm concentration, total sperm count, and the percentage of sperm motility. Twenty-five mg of Prednisone led to significant improvement in all the sperm parameters, except for semen volume. These results clearly demonstrate that Prednisone treatment can significantly improve sperm parameters in a selected population of oligozoospermic patients. These findings suggest that Prednisone treatment should be considered in idiopathic oligozoospermic patients with supposed normal spermatogenesis and accessory gland inflammatory alterations, in order to improve sperm parameters and fertility outcome.

Sperm telomere length as a parameter of sperm quality in normozoospermic men.

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 = 0.004) and vitality (P = 0.007). STL was significantly and negatively associated with sperm DNA fragmentation (P = 0.001) and significantly and positively associated with protamination (P = 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 INTERESTS: No external funding was either sought or obtained for this study. There are no conflicts of interest to be declared.

Altered chemokine signalling in endothelial progenitor cells from acute ulcerative colitis patients.

Ulcerative colitis (UC) is a chronic, idiopathic, inflammatory bowel disease, characterized by alternating stages of clinically active and inactive disease. UC exhibits several inflammatory characteristics, including immune activation, leukocyte infiltration, and altered vascular density. In UC, many of the upregulated inflammatory cytokines are proangiogenic and are released by diverse cell populations, such as infiltrating immune cells and endothelial cells (EC). Increasing evidences suggest that neovascularisation may involve also endothelial progenitor cells (EPCs). In this study we evaluated EPCs recruitment and homing, assessed by CXCR4 expression, in both acute and remitting phase of UC. We report an overall decrease of EPCs in UC patients (controls = 97,94 ± 37,34 cells/mL; acute = 31,10 ± 25,38 cells/mL; remitting = 30,33 ± 19,02 cells/mL; P < 0.001 for both UC groups versus controls). Moreover CXCR4(+)-EPCs, committed to home in inflammatory conditions, were found to be reduced in acute UC patients compared to both remitting patients and controls (acute = 3,13 ± 4,61 cells/mL; controls = 20,12 ± 14,0; remitting = 19,47 ± 12,83; P < 0,001). Interestingly, we found that administration of anti-inflammatory drugs in acute UC is associated with an increase in circulating EPCs, suggesting that this therapy may exert a strong influence on the progenitor cells response to inflammatory processes.

HPV-DNA sperm infection and infertility: from a systematic literature review to a possible clinical management proposal.

The objectives of this study were to investigate the implications of human papillomavirus (HPV) sperm infection on male fertility, impairment of sperm parameters, and possible alteration of sperm nuclear status and to identify a possible effective management of infertile men with HPV sperm infection. We employed a systematic review and clinical management proposal at the Centers for Reproductive and Health care for treating infertile male patients with HPV infection. Literature search was carried out in electronic databases in the last two decades. We focused our attention on: (i) HPV sperm prevalence (ii) HPV-related alteration of sperm parameters; (iii) molecular mechanisms of HPV semen infection and infertility. The main outcome measures were HPV prevalence in infertile male patients and semen parameters. The prevalence of HPV sperm infection ranges between 2 and 31% in men from general population and between 10 and 35.7% in men affected by unexplained infertility. The presence of HPV in semen is associated with an impairment of sperm motility and the presence of anti-sperm antibodies. The molecular mechanisms underlying impairment of sperm motility apparatus need further evaluations. A greater attention should be applied to assess HPV sperm infection, particularly in men undergoing assisted reproduction techniques cycle for male infertility or sperm banking. It would be useful to perform HPV test and fluorescent in situ hybridization analysis for HPV in semen from these patients both at first admission, to define the possible presence and localization of semen infection, and after 6 months, to assess the possible virus clearance retrieval on normal sperm parameters.

Platelets express and release osteocalcin and co-localize in human calcified atherosclerotic plaques.

BACKGROUND: Although vascular-calcification mechanisms are only partially understood, the role of circulating calcifying cells and non-collagenous bone matrix proteins in the bone-vascular axis is emerging. In spite of the fact that platelets represent a cellular interface between hemostasis, inflammation and atherosclerosis, and have a myeloid precursor, a possible involvement in the modulation of vascular calcification has rarely been investigated. We investigated if osteocalcin (OC) is released by platelets and described OC expression in patients with carotid artery occlusive disease. METHODS: Expression and release of OC were determined by Western blot, immunofluorescence, fluorescence-activated cell sorting (FACS) and ELISA in human resting and activated platelets and megakaryocytes. Co-localization of platelet aggregates, macrophages, OC and calcifications was studied in carotid endarterectomy specimens and normal tissues. RESULTS: Human platelets expressed OC and co-localized with CD63 in δ-granules. Upon activation with an endogenous mechanism, platelets released OC in the extracellular medium. Expression of OC in megakaryocytes suggested lineage specificity. The OC count in circulating platelets and the released amount were significantly higher in patients with carotid artery occlusive disease than in healthy controls (P < 0.0001) in spite of similar serum levels. In atherosclerotic plaques, OC strongly overlapped with CD41+ platelets in the early stage of calcification, but this was not seen in normal tissues. CD68+OC+ cells were present at the periphery of the calcified zone. CONCLUSIONS: Given the active role played by platelets in the atherosclerotic process, the involvement of OC release from platelets in atherosclerotic lesions and the impact of genetic and cardiovascular risk factors in mediating bone-marrow preconditioning should be investigated further.

Anthropometric, penile and testis measures in post-pubertal Italian males.

BACKGROUND: Relationships between anthropometric measures, body proportions, weight and penile dimensions in young adult males have not been previously analyzed. Furthermore, although male fertility has declined in last decades, no data on testicular volume (the best surrogate measure for spermatogenic potential) are available for the general population of young men in Italy. AIM: To analyze anthropometric measures and proportions, testicular volumes, and penile dimensions in a large cohort from the general population of young Italian men aged 18-19 yr. MATERIALS/SUBJECTS: We analyzed 2019 students aged 18-19 years for height, weight, body mass index (BMI), waist circumference, arm span, pubis-to-floor and crown-to-pubis length, and penile dimensions. Testicular volumes were measured by ultrasound in 776 subjects. RESULTS: Thirty-six percent of the subjects had a pathological arm span-height difference (>3 cm) and 44.7% had a pathological pubis-to-floor/ crown-to-pubis ratio (≤ 0.92). The mean penis length was 8.9 ± 1.4 cm and the penis circumference was 9.5 ± 1.0 cm. BMI was positively associated with arm span-height difference and negatively with penis length; 23.2% of the subjects had low mean testicular volume (<12 ml). CONCLUSIONS: The findings highlight a strong influence of BMI on skeletal proportions and penis length, identify a large proportion of subjects with testicular hypotrophy at risk for future fertility, and suggest to consider worldwide studies to redefine normal values for arm span-height difference and upper/ lower body segment ratio.

Altered bone status in unilateral testicular cancer survivors: Role of CYP2R1 and its luteinizing hormone-dependency.

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.