Three-Dimensional Power Doppler Vascularization in Women With Ovarian Endometriomas and Relationship With Associated Painful Symptoms.

OBJECTIVES: The objective of the study was to evaluate the correlation between endometrioma-associated pain and lesion vascularization as measured with 3-dimensional power Doppler transvaginal sonography. METHODS: Endometriomas were examined, and 4 indices were obtained: mean grayness, flow index, vascularization index, and vascularization-flow index. Dysmenorrhea, chronic pelvic pain, and dyspareunia were analyzed in terms of severity, presence/absence, and duration. RESULTS: Twenty-nine women were selected. The univariable association of painful symptoms in terms of presence/absence and duration was low with the exception of mean grayness with the presence of chronic pelvic pain (ß = -0.106; P = .047; 95% confidence interval, 0.810 to 0.998). The R2 value increased to 0.226 for dysmenorrhea (ß = -0.475; P = .029) when analyzing the association between the vascularization index and the severity of painful symptoms. The visual analog scale scores for chronic pelvic pain and dyspareunia were higher (R2 = 0.300; ß = -0.547 and -0.548, respectively; P = .028 and .053). CONCLUSIONS: We observed an inverse association between the severity of pain and endometrioma vascularization. Further larger studies are required to confirm our findings.

Sperm glyceraldehyde 3-phosphate dehydrogenase gene expression in asthenozoospermic spermatozoa.

It has been suggested that the energy required for sperm motility is produced by oxidative phosphorylation while glycolysis seems to be an important source for ATP transmission along the flagellum. Some studies have investigated the chemical and kinetic properties of the enzyme glyceraldehyde 3-phosphate dehydrogenase to identify any changes in the regulation of glycolysis and sperm motility. In contrast, there are few studies analyzing the genetic basis of hypokinesis. For this reason, we investigated the glyceraldehyde 3-phosphate dehydrogenase gene in human sperm to evaluate whether asthenozoospermia was correlated with any changes in its expression. Semen examination and glyceraldehyde 3-phosphate dehydrogenase gene expression studies were carried out on 116 semen samples divided into two groups - Group A consisted of 58 normokinetic samples and Group B of 58 hypokinetic samples. Total RNA was extracted from spermatozoa, and real-time PCR quantification of mRNA was carried out using specific primers and probes. The expression profiles for the Groups A and B were very similar. The mean delta Ct was as follows - Group A, 5.79 ± 1.04; Group B, 5.47 ± 1.27. Our study shows that in human sperm, there is no difference in glyceraldehyde 3-phosphate dehydrogenase gene expression between samples with impaired motility and samples with normal kinetics. We believe that this study could help in the understanding of the molecular mechanisms of sperm kinetics, suggesting that hypomotility may be due to a possible posttranscriptional impairment of the control mechanism, such as mRNA splicing, or to posttranslational changes.

Sperm DNA fragmentation in Italian couples with recurrent pregnancy loss.

The aetiopathogenesis of recurrent pregnancy loss (RPL) is heterogeneous. The aim of this study was to investigate the male factor in Italian couples experiencing RPL following natural conception. The study investigated 112 men from RPL couples and two control groups: 114 infertile men with one or more impaired semen parameters and 114 fertile men with high-quality semen parameters. Semen parameters were examined according to WHO criteria. Sperm DNA fragmentation (SDF) was evaluated using TdT-mediated dUDP nick-end labelling (TUNEL) assay. With the exception of ejaculate volume, the seminal profile of patients with RPL was similar to that of fertile patients and better than the infertile ones. Despite good spermatogenesis, however, sperm DNA integrity was impaired in the RPL group, with SDF values significantly higher than in fertile controls (18.8 ± 7.0 versus 12.8 ± 5.3, P < 0.001) and similar to those of infertile patients. SDF also showed a positive correlation with the age of patients with RPL and number of miscarriages. The results suggest a correlation between increased SDF and impaired reproductive capacity in terms of both fertilization and pregnancies carried to term, but high SDF cannot yet be considered a predictive factor for the risk of RPL.

Differential expression of miRNAs in the seminal plasma and serum of testicular cancer patients.

Various microRNAs from the miR-371-3 and miR-302a-d clusters have recently been proposed as markers for testicular germ cell tumours. Upregulation of these miRNAs has been found in both the tissue and serum of testicular cancer patients, but they have never been studied in human seminal plasma. The aim of this study was, therefore, to assess the differences in the expression of miR-371-3 and miR-302a-d between the seminal plasma and serum of testicular cancer patients, and to identify new potential testicular cancer markers in seminal plasma. We investigated the serum and seminal plasma of 28 pre-orchiectomy patients subsequently diagnosed with testicular cancer, the seminal plasma of another 20 patients 30 days post-orchiectomy and a control group consisting of 28 cancer-free subjects attending our centre for an andrological check-up. Serum microRNA expression was analysed using RT-qPCR. TaqMan Array Card 3.0 platform was used for microRNA profiling in the seminal plasma of cancer patients. Results for both miR-371-3 and the miR-302 cluster in the serum of testicular cancer patients were in line with literature reports, while miR-371and miR-372 expression in seminal plasma showed the opposite trend to serum. On array analysis, 37 miRNAs were differentially expressed in the seminal plasma of cancer patients, and the upregulated miR-142 and the downregulated miR-34b were validated using RT-qPCR. Our study investigated the expression of miRNAs in the seminal plasma of patients with testicular cancer for the first time. Unlike in serum, miR-371-3 cannot be considered as markers in seminal plasma, whereas miR-142 levels in seminal plasma may be a potential marker for testicular cancer.

Treatment with human, recombinant FSH improves sperm DNA fragmentation in idiopathic infertile men depending on the FSH receptor polymorphism p.N680S: a pharmacogenetic study.

STUDY QUESTION: Does the sperm DNA fragmentation index (DFI) improve depending on the FSH receptor (FSHR) genotype as assessed by the nonsynonymous polymorphisms rs6166 (p.N680S) after 3 months of recombinant FSH treatment in men with idiopathic infertility? SUMMARY ANSWER: FSH treatment significantly improves sperm DFI only in idiopathic infertile men with the p.N680S homozygous N FSHR. WHAT IS KNOWN ALREADY: FSH, fundamental for spermatogenesis, is empirically used to treat male idiopathic infertility and several studies suggest that DFI could be a candidate predictor of response to FSH treatment, in terms of probability to conceive. Furthermore, it is known that the FSHR single nucleotide polymorphism (SNP) rs6166 (p.N680S) influences ovarian response in women and testicular volume in men. STUDY DESIGN, SIZE AND DURATION: A multicenter, longitudinal, prospective, open-label, two-arm clinical trial was performed. Subjects enrolled were idiopathic infertile men who received 150 IU recombinant human FSH s.c. every other day for 12 weeks and were followed-up for a further 12 weeks after FSH withdrawal. Patients were evaluated at baseline, at the end of treatment and at the end of follow-up. PARTICIPANTS/MATERIALS, SETTING, METHODS: Eighty-nine men with idiopathic infertility carrier of the FSHR p.N680S homozygous N or S genotype, FSH ≤ 8 IU/l and DFI >15%, were enrolled. A total of 66 patients had DFI analysis completed on at least two visits. DFI was evaluated in one laboratory by TUNEL/PI (propidium iodide) assay coupled to flow cytometry, resolving two different fractions of sperm, namely the 'brighter' and 'dimmer' sperm DFI fractions. MAIN RESULTS AND THE ROLE OF CHANCE: Thirty-eight men (57.6%) were carriers of the p.N680S homozygous N and 28 (42.4%) of the homozygous S FSHR. Sperm concentration/number was highly heterogeneous and both groups included men ranging from severe oligozoospermia to normozoospermia. Total DFI was significantly lower at the end of the study in homozygous carriers of the p.N680S N versus p.N680S S allele (P = 0.008). Total DFI decreased significantly from baseline to the end of the study (P = 0.021) only in carriers of the p.N680S homozygous N polymorphism, and this decrease involved the sperm population containing vital sperm (i.e. brighter sperm) (P = 0.008). The dimmer sperm DFI fraction, including only nonvital sperm, was significantly larger in p.N680S S homozygous patients than in homozygous N men (P = 0.018). Total DFI was inversely related to total sperm number (P = 0.020) and progressive sperm motility (P = 0.014). When patients were further stratified according to sperm concentration (normoozospermic versus oligozoospermic) or -211G>T polymorphism in the FSHB gene (rs10835638) (homozygous G versus others), the significant improvement of sperm DFI in FSHR p.N680S homozygous N men was independent of sperm concentration and associated with the homozygous FSHB -211G>T homozygous G genotype. LIMITATIONS, REASONS FOR CAUTION: The statistical power of the study is 86.9% with alpha error 0.05. This is the first pharmacogenetic study suggesting that FSH treatment induces a significant improvement of total DFI in men carriers of the p.N680S homozygous N FSHR; however, the results need to be confirmed in larger studies using a personalized FSH dosage and treatment duration. WIDER IMPLICATIONS OF THE FINDINGS: The evaluation of sperm DFI as a surrogate marker of sperm quality, and of the FSHR SNP rs6166 (p.N680S), might be useful to predict the response to FSH treatment in men with idiopathic infertility. STUDY FUNDING/COMPETING INTERESTS: The study was supported by an unrestricted grant to M.S. and H.M.B. from Merck Serono that provided the drug used in the study. MS received additional grants from Merck Serono and IBSA as well as honoraria from Merck Serono. The remaining authors declare that no conflicts of interest are present. TRIAL REGISTRATION NUMBER: EudraCT number 2010-020240-35.

Influence of CAG Repeat Polymorphism on the Targets of Testosterone Action.

In the last decade, ample evidence has demonstrated the growing importance of androgen receptor (AR) CAG repeat polymorphism in andrology. This genetic parameter is able to condition the peripheral effects of testosterone and therefore to influence male sexual function and fertility, cardiovascular risk, body composition, bone metabolism, the risk of prostate and testicular cancer, the psychiatric status, and the onset of neurodegenerative disorders. In this review, we extensively discuss the literature data and identify a role for AR CAG repeat polymorphism in conditioning the systemic testosterone effects. In particular, our main purpose was to provide an updated text able to shed light on the many and often contradictory findings reporting an influence of CAG repeat polymorphism on the targets of testosterone action.

Is there a critical endometrioma size associated with reduced ovarian responsiveness in assisted reproduction techniques?

This study investigated the relationships between ovarian endometrioma size, ovarian responsiveness and the number of retrieved oocytes following ovarian stimulation. A prospective study was conducted in a public clinical assisted reproduction centre. A total of 64 infertile women with monolateral endometriomas undergoing IVF or intracytoplasmic sperm injection were included in the study. The total number of follicles, number of follicles ≥ 16 mm and number of oocytes retrieved of ovaries containing endometrioma and normal ovaries were compared. Multivariate linear regression was used to assess whether number of follicles and collected oocytes varied by endometrioma size, age, basal FSH concentration. Significantly lower numbers of follicles ≥ 16 mm (P = 0.024) and oocytes retrieved (P = 0.001) in the ovaries containing endometrioma were observed. In patients with endometriomas ≥ 30 mm, endometrioma size was the most influential contributor to the total number of follicles and oocytes retrieved. Ovarian endometriomas result in reduced response to ovarian stimulation, compared with the response of the contralateral normal ovary in the same individual. In case of endometriomas <30 mm, basal FSH concentration remains the most important prognostic factor for oocyte retrieval.

Sperm cryopreservation: effects on chromatin structure.

Cryopreservation is a technique that can keep sperm alive indefinitely, enabling the conservation of male fertility. It involves the cooling of semen samples and their storage at -196°C in liquid nitrogen. At this temperature all metabolic processes are arrested. Sperm cryopreservation is of fundamental importance for patients undergoing medical or surgical treatments that could induce sterility, such as cancer patients about to undergo genotoxic chemotherapy or radiotherapy, as it offers these patients not only the hope of future fertility but also psychological support in dealing with the various stages of the treatment protocols.Despite its importance for assisted reproduction technology (ART) and its success in terms of babies born, this procedure can cause cell damage and impaired sperm function. Various studies have evaluated the impact of cryopreservation on chromatin structure, albeit with contradictory results. Some, but not all, authors found significant sperm DNA damage after cryopreservation. However, studies attempting to explain the mechanisms involved in the aetiology of cryopreservation-induced DNA damage are still limited. Some reported an increase in sperm with activated caspases after cryopreservation, while others found an increase in the percentage of oxidative DNA damage. There is still little - and contradictory - information on the mechanism of the generation of DNA fragmentation after cryopreservation. More studies are needed to establish the true importance of such damage, especially to improve the results of ART.

Effect of endogenous and exogenous hormones on testicular cancer: the epidemiological evidence.

Testicular cancer is the most common type of malignancy in men aged 15-40 years. Although its incidence has increased over the past 40 years in most countries, the reasons for this rise are unclear. It has been suggested that a relative excess of endogenous estrogens during prenatal life and/or later exposures to various occupational and environmental estrogenic chemicals such as organochlorine compounds may play a causal role in the etiology of testicular cancer, but the issue is still open to further research. The purpose for this review is to summarize the epidemiologic literature about hormonal factors, endogenous hormones and environmental xenoestrogens, and testicular carcinogenesis. Future studies need to (a) consider the possible synergistic effect of exposure to environmental xenoestrogens and sex hormones, (b) focus on the most vulnerable life stages of exposure to endocrine disruptors and testicular cancer risk, (c) assess the possible additive role of androgen secretion occurring during puberty in tumor progression, and (d) consider more systematically gene-environment interactions.

Case-control study of anthropometric measures and testicular cancer risk.

The etiology of testicular germ cell tumors (TGCTs) is poorly understood. Recent epidemiological findings suggest that, TGCT risk is determined very early in life, although the available data are still conflicting. The rapid growth of the testes during puberty may be another period of vulnerability. Body size has received increasing attention as possible risk factor for TC. To clarify the relation of body size and its anthropometric variables to TGCT risk, the authors analyzed data from 272 cases and 382 controls with regard to height (cm), weight (Kg), and body mass index (BMI; kg/m(2)). Overall, participants in the highest quartile of height were more likely to be diagnosed with TGCTs than participants in the lowest quartile of height, OR 2.22 (95% confidence intervals (CI): 1.25-3.93; adjusted; p(trend) = 0.033). Moreover, histological seminoma subgroup was significantly associated with tallness, very tall men (>182 cm) having a seminoma TGCT risk of OR = 2.44 (95% confidence intervals (CI): 1.19-4.97; adjusted; p(trend) = 0.011). There was also a significant inverse association of TGCT with increasing BMI (p(trend) = 0.001; age-adjusted analysis) and this association was equally present in both histological subgroups. These preliminary results indicate that testicular cancer (TC) is inversely associated with BMI and positively associated with height, in particular with seminoma subtype. Several studies have reported similar findings on body size. As adult height is largely determined by high-calorie intake in childhood and influenced by hormonal factors at puberty, increased attention to postnatal exposures in this interval may help elucidate the etiology of TGCTs.

Higher clusterin immunolabeling and sperm DNA damage levels in hypertensive men compared with controls.

BACKGROUND: Clusterin, a heterodimeric glycoprotein found at several sites in the human male reproductive tract, could be a marker of morphologically abnormal spermatozoa, while TUNEL positivity indicates DNA fragmentation. Metabolic disorders such as diabetes mellitus and obesity may compromise sperm quality and fertility of men; however, little evidence specifically links hypertension with the impairment of male reproductive function. METHODS: By flow cytometric, immunofluorescence (TUNEL assay and clusterin immunolabeling) and immunohistochemical (peroxidase-streptavidin method) analyses, we have compared both clusterin- and TUNEL labeling in ejaculated spermatozoa from healthy normotensive donors and hypertensive subjects with the purpose to reveal possible differences between the two conditions. RESULTS: Data analysis from the normotensive (n=25) and hypertensive subjects (n=25) demonstrate a significant correlation between high levels of clusterin immunolabeling and the presence of sperm DNA damage, which is often associated with abnormal morphology. In the normotensive subjects, a low percentage (15.3±4.5) of spermatozoa positive for high levels of clusterin was detected; however, this percentage significantly increased (30.9±13.0) (P<0.01) in hypertensive subjects. Standard semen evaluations does not reveal any significant differences between the two groups of subjects, except for a reduced forward motility and lower sperm vitality in the hypertensive subjects. CONCLUSIONS: This pilot study strongly suggests a relationship between hypertension and markers indicative of poor sperm quality. In hypertensive subjects, high levels of clusterin immunolabeling identified a consistent fraction of ejaculated spermatozoa carrying both DNA fragmentation and strong morphological alterations, which was not correlated with age or with sperm cell mortality. The alternative possibility that sperm damage observed is due to adverse effects of anti-hypertensive drugs does not find support in the literature nor in the drug data sheets. The relationship observed between hypertension and human semen represents a novel and possibly relevant information to be considered in the study of male fertility.

Pesticide exposure and serum organochlorine residuals among testicular cancer patients and healthy controls.

The incidence of testicular cancer (TC) has been increasing worldwide during the last decades. The reasons of the increase remains unknown, but recent findings suggest that organochlorine pesticides (OPs) could influence the development of TC. A hospital-based case-control study of 50 cases and 48 controls was conducted to determine whether environmental exposure to OPs is associated with the risk of TC, and by measuring serum concentrations of OPs, including p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) isomer and hexachlorobenzene (HCB) in participants. A significant association was observed between TC and household insecticide use (odds ratio [OR] = 3.01, 95 % CI: 1.11-8.14; OR(adjusted) = 3.23, 95 % CI: 1.15-9.11). Crude and adjusted ORs for TC were also significantly associated with higher serum concentrations of total OPs (OR = 3.15, 95 % CI: 1.00-9.91; OR(adjusted) = 3.34, 95 % CI: 1.09-10.17) in cases compared with controls. These findings give additional support to the results of previous research that suggest that some environmental exposures to OPs may be implicated in the pathogenesis of TC.

The role of antioxidant therapy in the treatment of male infertility: an overview.

In recent years, many studies have focused on the effect of oxidative stress, reactive oxygen species (ROS) and antioxidants on the male eproductive system. Under physiological conditions, sperm produces small amounts of ROS, which are needed for fertilisation, acrosome reaction and capacitation. However, if an increased production of ROS is not associated with a similar increase in scavenging systems, peroxidative damage of the sperm plasma membrane and loss of DNA integrity typically occur, which leads to cell death and reduced fertility. Furthermore, since there is no linear correlation between sperm quality and pregnancy rates, an improvement in semen parameters should not be the sole outcome considered in studies of antioxidant therapies. A definitive conclusion regarding the benefit of these therapies is difficult to obtain, as most of the previous studies lacked control groups, considered different antioxidants in different combinations and doses, or did not evaluate pregnancy rates in previously infertile couples. Even if beneficial effects were reported in a few cases of male infertility, more multicentre, double-blind studies performed with the same criteria are necessary for an increased understanding of the effects of various antioxidants on fertility.

Activation of the immune system and sperm DNA fragmentation are associated with idiopathic oligoasthenoteratospermia in men with couple subfertility.

Ejaculates from men without known causes for male subfertility and asymptomatic for genital tract inflammation showed infiltration of macrophages, and their activation state (HLA-DR(+)) was negatively correlated with semen parameters and positively correlated with sperm DNA damage. An activation of the immune system is thus detectable in idiopathic oligoasthenoteratozoospermia of unknown origin.

Mitochondrial membrane potential profile and its correlation with increasing sperm motility.

OBJECTIVE: To investigate sperm mitochondrial integrity through analysis of mitochondrial membrane potential (Δψ) and to correlate the energy status with variations in sperm motility. DESIGN: Experimental study. SETTING: Seminology Laboratory, University of Rome, Italy. PATIENT(S): Two hundred thirteen semen samples from the same number of patients, divided into two groups on the basis of their motility: group A, 185 samples with linear motility and group B, 28 samples with nonlinear motility. INTERVENTION(S): Evaluation of sperm motility. MAIN OUTCOME MEASURE(S): Sperm mitochondrial integrity evaluated with a fluorimetric method using the cationic lipophilic stain JC-1. RESULT(S): The mean FL2 (percentage of sperm with high and low ∆ψ) for group A was 46.19±23.25 and for group B, it was 48.32±24.43. There was no significant difference between the groups. There was a positive correlation between both FL2 and linear motility and FL2 and sperm vitality in group A; both correlations were statistically significant. In group B, there was a positive correlation between FL2 and nonlinear motility and FL2 and sperm vitality; again, both correlations were statistically significant. CONCLUSION(S): Our data reveal a positive correlation between total motility and Δψ, suggesting that sperm motility may be dependent on the functional integrity of the mitochondria.

Expression and localization of the sodium/iodide symporter (NIS) in testicular cells.

Administration of radioiodine (I(131)) is currently exploited for both diagnostic and therapeutic treatment of thyroid cancer. Few data are available on the sodium/iodide symporter (NIS) expression in human testis, a particular important prerequisite to predict radioiodine accumulation in the gonads of males with thyroid cancer exposed to such a treatment. In this study, we analyzed the expression of NIS in mouse, rat and human normal testis in different stages of development. By using a quantitative RT-PCR, Western blot and immunohistochemical analysis, NIS mRNA and protein were measured in both fetal and adult testicular tissues. NIS transcript was detected in both fetal and adult testis, although its expression levels were approximately 10-fold less than in thyroid gland. Western blot analysis and immunohistochemistry showed the presence of NIS protein in germinal and Leydig cells, but not in Sertoli cells with prevalent expression in the cytosol compartment of the cells. Our study demonstrates that NIS transcript and protein are expressed in normal testis. Further studies will demonstrate whether it may act as the transporter of radioiodine in normal testis of male patients with thyroid cancer.

Altered ultrastructure of mitochondrial membranes is strongly associated with unexplained asthenozoospermia.

OBJECTIVE: To explore the contribution of an altered structure of sperm mitochondria to human asthenozoospermia. DESIGN: A retrospective study. SETTING: Andrology Clinic, University of L'Aquila. PATIENT(S): Fifteen ejaculates with forward motility (FM) ≥ 50%, and 57 asthenozoospermic ejaculates (FM <50%, sperm vitality >50%), including 14 ejaculates with systematic genetic defects of tail principal piece, and 43 ejaculates with unexplained asthenozoospermia. INTERVENTION(S): Fifty sections of tail middle piece (MP) were blindly analyzed by transmission electron microscopy in each ejaculate for normal mitochondrial membrane organization, after exclusion of tails with disrupted cell membranes. MAIN OUTCOME MEASURE(S): Percentage of MPs with normal mitochondrial membranes (% normal MPs). RESULT(S): Percent normal MPs showed a strong correlation with forward motility. Variation of % normal MPs explained a 45% variation of sperm motility at multivariate linear regression analysis, confirming the strong association between the two parameters in a population including ejaculates with normal motility and with unexplained asthenozoospermia. Percent normal MPs was significantly reduced in severe unexplained asthenozoospermia (FM <10%; n = 16) compared with samples with normal motility (FM ≥ 50%; n = 15); 21% (10.5%-38%) and 68% (52%-73%), respectively. CONCLUSION(S): Structural defects in mitochondrial membranes represent a main feature of severe unexplained asthenozoospermia.

Expression of a truncated form of KIT tyrosine kinase in human spermatozoa correlates with sperm DNA integrity.

BACKGROUND: TR-KIT, a truncated form of KIT (the KITL receptor), corresponding to the c-terminal half of the intracellular split tyrosine kinase domain, is expressed during the haploid stages of mouse spermatogenesis, and is one of the candidate sperm factors possibly involved in egg activation at fertilization. METHODS: Immunocytochemistry of adult human testis, and studies of human semen samples from volunteer donors through immunofluorescence, confocal microscopy, flow cytometry, western blot and RT-PCR analyses were performed. RESULTS: We show that the TR-KIT is expressed during spermiogenesis in the human testis, and that it is maintained in human ejaculated spermatozoa. TR-KIT is localized both in the equatorial segment and in the sub-acrosomal region of the human sperm head. The equatorial localization of the TR-KIT persists after the spontaneous acrosome reaction. Cytometric analysis of several sperm samples from volunteer donors, showed variable degrees of the TR-KIT-specific immunolabeling, and a significant inverse correlation (Pearson's coefficient, r = -0.76, P < 0.0001, n = 23) of the TR-KIT positivity with markers of sperm damage, i.e. DNA fragmentation, as revealed by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labeling (TUNEL) analysis and the intense clusterin positivity. We also found less significant inverse correlation with altered head morphology (r = -0.47, P < 0.05, n = 23) and direct correlation with sperm forward motility parameters (r = 0.59, P < 0.01, n = 23). CONCLUSIONS: The TR-KIT is present in the equatorial region of human spermatozoa, which is the first sperm component entering into the oocyte cytoplasm after fusion with the egg. This localization is consistent with the function previously proposed for this protein in mice. In addition, the TR-KIT represents a potential predictive parameter of human sperm quality.

Clinical and laboratoristic strategy in late onset hypogonadism.

Aging in men is associated with a gradual and progressive decline in serum total testosterone concentrations as a result of primary testicular and secondary hypothalamic-pituitary dysfunction. Androgen secretion does not cease, it gradually decreases but usually continues at some level. A diagnosis of hypogonadism should rely on both symptoms and laboratory tests. Declining testosterone levels with age are primarily due to changes in the testes, which show decreases in the number of Leydig cells, the activity of enzymes that contribute to testosterone production, and the ability to increase testosterone production in response to gonadotropin stimulation. Physicians should also take note of symptoms indicatine age-related complaints. Validated questionnaires can be helpful. Administration of androgens appears to improve positive aspects of mood. Hypogonadism is also a risk factors for osteoporosis. Aging is associated with a reduction in sexual activity. T and DHT appear to be essential for development and maintenance of libido or sexual desire, and they probably have a direct effect on penile erections. Testosterone replacement therapy (TRT) affects nocturnal erections and penile rigidity in hypogonadal males. It is not known whether TRT will increase the risk of prostate cancer. The influence of T on prostate carcinogenesis and other prostate outcomes remains poorly defined. The aim of treatment for hypogonadism is to normalize serum testosterone levels and abolish symptoms or pathological states that are due to low testosterone levels. The exact target testosterone level is a matter of debate, but current recommendations advocate levels in the mid-lower normal adult range.

HDL cholesterol is a strong determinant of endothelial progenitor cells in hypercholesterolemic subjects.

Endothelial progenitor cells (EPC) can repair the endothelial layer and are considered a component of the cardiovascular system. EPC number and function may change under pathological conditions, including cardiovascular risk factors. The study was carried out to investigate circulating EPC number, in vitro function and relationship with LDL-C, HDL-C and endothelium-dependent vasodilatation in hypercholesterolemic subjects. Forty-one male and 39 female subjects, age>35 and<45, LDL cholesterol plasma level>130 mg/dl with normal (> or =50 mg/dl females and> or =40 mg/dl males) or low HDL-C, absence of any concomitant disorders and/or drug treatment, at their first diagnosis of hypercholesterolemia, were consecutively recruited in the Outpatient Service of the Medical Pathophysiology Department of Rome Sapienza University. In high LDL-C patients, circulating EPC number was decreased and EPC capability to migrate was impaired as well. This pattern was far less evident in the normal HDL-C subgroup. The endothelium-dependent vasodilatation (EDV) was significantly decreased according to the HDL-C decrease in male but not in female subjects. Univariate analysis showed a direct correlation between EPC number and EDV, and the association persisted after adjustment for sex, age and HDL-C, which were all significantly correlated to EDV, which may suggest a protective role of EPC on endothelium in vivo. Our study documented that, in hypercholesterolemic subjects, HDL-C is a strong determinant of EPC number and function, and EPC number decrease is an independent risk factor for endothelial dysfunction.