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.

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.

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.

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.

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.

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.

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 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.

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.

Effects of endogenous FSH on normal human spermatogenesis in adults.

Unilateral orchiectomy (UO) in adult bonnet monkeys and boars elicits a compensatory increase in size and sperm production of the remaining testis. The objective of this study was to investigate whether a similar effect is evident also in humans. We prospectively studied 50 patients from October 2003 to December 2005 who underwent UO for seminomatous tumour, with sperm concentration >20 × 10(6) /mL or total sperm count >40 × 10(6) at diagnosis and without elevation of serum tumour markers. Patients were followed-up with surveillance and they were studied at the time of diagnosis of testicular cancer (T(-1) ), 1 month after unilateral orchiectomy (T(0) ) and yearly for 3 years (T(1) , T(2) , T(3) ) with semen analysis, measurement of plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), inhibin B, total testosterone, and oestradiol and ultrasonographic scanning of the remaining testis. A decline in circulating inhibin B and an increase in FSH levels were evident 1 month after UO. The elevation of FSH was maintained up to 3 years and was associated with a significant increase in testicular volume of 19 and 30%, 2 and 3 years after UO respectively. Although patients had normozoospermia at the time of diagnosis of testicular cancer, they showed a statistically significant increase in total sperm count at T(2) and T(3) with respect to T(-1) and T(0.) In conclusion, we showed that in humans, the testes are not normally operating at their maximal potential in terms of spermatogenesis. Therefore, in physiological situations, FSH secretion is insufficient to stimulate spermatogenesis to its ceiling. A sustained endogenous increase in FSH secretion might drive human testes towards their maximal function.

The response to FSH treatment in oligozoospermic men depends on FSH receptor gene polymorphisms.

In the last years, follice-stimulating hormone (FSH) receptor (FSHR) gene polymorphisms have been studied as potential risk factors for spermatogenetic failure. In this study, we have evaluated the response of FSH treatment in terms of sperm production on the basis of Ala307Thr-Asn680Ser polymorphisms in the FSHR gene in a group of oligozoospermic subjects with hypospermatogenesis and normal FSH levels. Patients were randomized into two groups: 70 treated with recombinant FSH (150 IU thrice per week for 3months) and 35 without treatment. After 3months of treatment, we observed significant increase in total sperm count, sperm concentration, forward motility, percentage of normal morphology forms and total motile sperm. When 70 treated subjects were subdivided based on FSHR genotype, only subjects with at least one serine in position 680 showed a statistically significant increase in these sperm parameters, whereas subjects with homozygote Thr307-Asn680 showed no difference in any seminal parameters evaluated. Non-treated subjects showed no differences in any parameter evaluated. This study suggests that the analysis of this gene represents a valid pharmacogenetic approach to the treatment of male infertility, confirming also the importance of strict criteria for the selection of patients to be treated with FSH.

Human papilloma virus in the sperm cryobank: an emerging problem?

Human papilloma virus (HPV) infection is very common worldwide, but the actual incidence and significance of HPV infection in sperm are poorly understood. In this study, we evaluated the presence of HPV in spermatozoa from thawed semen samples previously stored in our sperm bank. We performed polymerase chain reaction and in situ hybridization for HPV detection in cryovials belonging to 98 oncology patients and in 60 semen samples from healthy controls. Statistical analysis was performed by two-tailed Student's t-test and Fisher's exact test. The frequency of HPV semen infection was 6.1% in thawed cryovials from patients and 3.3% in semen samples from controls. Among the patients, four were found positive for high-risk HPV, one for medium-risk HPV and another for low-risk HPV. Patients had a significantly higher percentage of infected sperm than controls. In conclusion, this report shows the presence of HPV in sperm cells from cryovials of a sperm bank. It is still unclear if HPV-infected sperm are able to cross-contaminate cryovials and impair the outcome of assisted reproduction techniques or to infect partners. Further studies are needed to understand whether screening for HPV should be performed in all semen samples before sperm banking or before intra-cytoplasmic sperm injection procedures.

How the human spermatozoa sense the oocyte: a new role of SDF1-CXCR4 signalling.

For fertilization to occur in mammals, ejaculated spermatozoa must reach the egg which, following ovulation has moved from the ovary into the Fallopian tube. Two active mechanisms of spermatozoa guidance have been shown in mammals: thermotaxis and chemotaxis. The identity of most of human spermatozoa chemoattractants is unknown, and herein we tested if SDF1 (chemokine stromal cell-derived factor-1) and its pathway is involved in spermatozoa chemotaxis. We found that SDF1 is expressed in the oocytes, endometrium and follicular fluid, as well as its specific receptor CXCR4 (chemokine CXC motif receptor 4) is expressed in the head of spermatozoa. By SDF1 gradient experiments, we stated that SDF1 is able to induce hyperactivation in spermatozoa leading to accumulation, to give rise to an increase in intracellular calcium concentration, and to preserve the mitochondrial status and not to induce acrosome reaction. Our findings suggest these phenomena could reflect spermatozoa chemotaxis, and that SDF1 action could represent an important event leading to egg fertilization, even if further studies regarding the link between spermatozoa accumulation and chemotaxis are mandatory. These data suggest that the SDF-1/CXCR4 signalling could be used to manipulate the human fertilization, to improve both the outcome of physiological or assisted reproduction, and to develop new contraceptive methods, by development of SDF1 or CXCR4 antagonist.

Increased osteocalcin-positive endothelial progenitor cells in hypogonadal male patients.

OBJECTIVE: Endothelial dysfunction is considered a key factor in the development of cardiovascular diseases. Endothelial regeneration is necessary for the maintenance of endothelial function and circulating endothelial progenitor cells (EPC) participate of it in both direct and indirect manner. The molecular phenotype of EPC is not univocally defined and recent studies identified an osteocalcin (OCN)-positive (EPC-OCN+) subpopulation of EPC highly correlated with atherosclerosis progression. AIM: Considering that hypogonadism is a risk factor for cardiovascular diseases and atherosclerosis, we investigated the circulating levels of EPC-OCN+ in hypogonadal patients. SUBJECTS AND METHODS: Ten hypogonadotropic hypogonadal (HH) male patients and 30 healthy eugonadal men were evaluated for clinical status and hormonal levels. Circulating levels of CD34+/CD133+/kinase insert domain-receptor+ EPC and EPC-OCN+ were also determined by flow cytometry. RESULTS: Compared to controls, HH patients displayed lower FSH, LH, estradiol, testosterone, and EPC levels. On the contrary, EPC-OCN+ were significantly increased. CONCLUSIONS: The observed association of low levels of circulating EPC and increased values of EPC-OCN+ sub-population in hypogonadal men strengthens the significance of hypogonadism as cardiovascular risk factor.

Spermatogenesis in Klinefelter syndrome.

BACKGROUND: Klinefelter syndrome (KS) (47,XXY) is the most common sex chromosomal disorder, and it is a frequent form of male hypogonadism and infertility. Although the majority of these patients are azoospermic, they might have severe oligozoospermia or residual single-residual foci with spermatogenesis in the testis. AIM: We report our experience on sperm retrieval in the ejaculate and testis, and evaluate the frequency of chromosome abnormalities in sperm of KS. SUBJECTS AND METHODS: Eighty-four 47,XXY KS were evaluated with seminal analysis, body hair distribution, reproductive hormones, ultrasonographic scanning of the testis and prostate, bilateral testicular sperm extraction (TESE), sperm or testicular cells sex chromosomes aneuploidies. RESULTS: Out of 84 patients, 7 (7/84; 8.3%) had sperm in the ejaculate. Out of the 77 azoospermic patients, 24 underwent TESE and 9 (9/24; 37.5%) had successful sperm recovery. The comparison of reproductive hormones, age and testicular volume did not show significant differences between patients with and without successful sperm recovery in semen or TESE . Patients without successful sperm recovery in semen analysis or TESE had signs of hypoandrogenism more evident than patients with successful sperm recovery. Patients with KS produced a higher number of sperm aneuploidy with respect to normozoospermic fertile controls and non-genetic severely oligozoospermic men. CONCLUSIONS: Men with KS are not always sterile. In some of these patients sperm can be found in semen or in the testis, but the proportion of sperm aneuploidy is high. Signs of hypoandrogenism seem to be associated with low sperm recovery rate.

Retraction: Expression of phosphodiesterase type 5A in human spermatozoa and influence of its inhibition on motility and functional sperm parameters.

The paper entitled "Expression of phosphodiesterase type 5A in human spermatozoa and influence of its inhibition on motility and functional sperm parameters" by C. Foresta et al, which was published online on 1 July 2010, has been withdrawn at the authors' request.

Clinical use of testicular fine needle aspiration cytology in oligozoospermic and azoospermic dogs.

Clinical investigation of canine testicular function is complicated by the difficulty in the evaluation of seminiferous tubules. Until recently, testicular biopsy was the only diagnostic option for dogs with persistent oligo/azoospermia. In human andrology, testicular fine needle aspiration (TFNA) is currently considered a useful method in the evaluation of azoospermia and severe oligozoospermia, and has long replaced classical biopsy to evaluate spermatogenesis. In order to verify its diagnostic efficacy for the clinical approach to canine oligo- or azoospermia, TFNA was performed in seven adult (two oligozoospermic and five azoospermic) dogs. After sedation, a fine (21-23 gauge) butterfly needle connected to a 50-ml syringe was inserted into each testicle; strong suction was applied and the aspirated fluid squirted on a glass slide, smeared out, air-dried and stained with a modified May-Grunwald-Giemsa. Under light microscopy, Sertoli cells (all those found in each investigated field) and spermatogenic cells (n = 100) were counted on each smear in order to differentiate spermatogonia, primary spermatocytes, secondary spermatocytes, early spermatids, late spermatids and spermatozoa, and calculate their relative percentages. Cytological analysis showed the following testicular pictures: normal spermatogenesis (compatible with obstruction of the seminal ducts), hypospermatogenesis, maturative disturbances and Sertoli cell-only syndrome. Two dogs with an obstructive lesion were treated with corticosteroids; one of them recovered and sired two litters of puppies.