7,650 research outputs found
Sperm DNA fragmentation testing as a diagnostic and prognostic parameter of couple infertility
No full textEditorial
No full textTesticular cancer (TC) is the most common cancer in males aged 20-40 years, with a worldwide incidence of 7.5 per 100,000, but the rates vary considerably between countries and ethnic groups and there is evidence also for an increasing incidence in last decades. About 95% of all TCs are represented by testicular germ cell tumors (TGCTs), which include seminoma and non-seminoma histological types. It is generally assumed that the development of TGCT is under endocrine control. In particular, unbalanced androgen/estrogen levels and/or activity are believed to represent the key events for TGCT development and progression. Furthermore, recent evidence has suggested genetic association of TGCT with variations in genes involved in hypothalamic-pituitary-testicular axis and steroidogenic enzymes. This recent evidence expands the current knowledge on the role of genetic contribution in testicular cancer susceptibility, and supports the hypothesis that variations in hormone metabolism genes might change the hormonal environment implicated in testicular carcinogenesis. Therefore, hormonal carcinogenesis is an important and controversial area of current research in TGCT, and further attention is given to genetic factors influencing hormone-related cancer risk. The genetic component to TGCT is in general strong. In fact, although environmental factors clearly contribute to TGCT development (and probably to its increasing incidence in some geographical areas), the proportion of TGCT susceptibility accounted for by the genetic effects is estimated at 25%. TGCT has high familial risks compared with most other cancer types that are generally no more than two-fold: brothers of individuals with TGCT have an 8- to 12-fold increased risk of disease, and sons of affected individuals have a 4- to 6-fold increased risk. Despite this strong familial relative risk, early results from linkage studies identified a limited relationship with genetic factors, suggesting that TGCT is a genetically complex trait. However, more recently, four genome-wide association studies (GWAS) from the UK and USA have reported association of TGCTs with six new loci (KITLG, SPRY4, BAK1, DMRT1, TERT, and ATF7IP). The strongest association for TGCT susceptibility was found for SNPs in KITLG (ligand for the membrane-bound receptor tyrosine kinase KIT) gene with a greater than 2.5-fold increased risk of disease per major allele, which is the highest reported for any cancer to date. These studies are being now replicated by other researches and attention is given to the relationship between these genetic variations, TGCT risk and frequently associated anomalies of the reproductive tract, such as cryptorchidism and infertility. Finally, over the past few decades, TCGT research has focused also on external environmental causes acting mainly as endocrine disrupters of androgen and oestrogen pathways, even during the foetal development of the testis. It is well known that the testicular dysgenesis syndrome (TDS) hypothesis, proposed ten years ago, suggests that disturbed testicular development in fetal life may result in one or more of four disorders postnatally, named cryptorchidism, hypospadias, poor semen quality, and TGCT. These four disorders are therefore considered as one clinical entity and are linked together by epidemiological and pathophysiological relations. The relative contribution of genetics and environment in TGCT development, and the interactions between endocrine disruptors and variations in genes involved in hormonal carcinogenesis is therefore another interesting area of research
The PDE5 Inhibitor Sildenafil Increases Circulating Endothelial Progenitor Cells and CXCR4 Expression
No full textINTRODUCTION:
Endothelial progenitor cells (EPC) are a specific subtype of progenitor cells that can be isolated from circulating mononuclear cells, able to migrate from the bone marrow to the peripheral circulation where they contribute to vascular repair. CXC-motif chemochine receptor 4 (CXCR4) receptor seems to play a critical role in this process.
AIM:
To assess the effects of sildenafil (a type 5 phosphodiesterase [PDE5] inhibitor) administration in 20 healthy young men.
METHODS:
Evaluation of CXCR4 expression in circulating EPC before and 4 hours after in vivo administration of 100 mg sildenafil by flow cytometry and colony-forming unit.
RESULTS:
We found that sildenafil increases circulating EPC number, the relative expression of CXCR4 on these cells and the ability to generate colonies in vitro.
CONCLUSIONS:
These data allow us to suppose an involvement of PDE5 in bone marrow release and peripheral homing of EPC
Lack of the T54A polymorphism of the DAZL gene in infertile Italian patients
No full textThe Thr54Ala polymorphism of the deleted-in-azoospermia-like (DAZL) protein has been associated with susceptibility to spermatogenic failure in the Taiwanese population. We used single-strand conformation polymorphism and restriction fragment analyses to investigate the presence of the A-->G transition in exon 3 of the DAZL gene in 95 infertile Italian patients. The patients had oligozoospermia or non-obstructive azoospermia with different degrees of testicular cytological picture. The allele carrying T54A polymorphism was not present in this group of patients nor in 63 controls, indicating that the frequency of this putative mutation is <1% in Italy. Since the Italian population usually shows allelic frequencies similar to the other Caucasian populations, we suggest that the T54A allele might play a role in infertility only in Taiwanese or Asiatic individuals
Y chromosome microdeletion in cryptorchidism and idiopathic infertility
No full textSettore ISI: Endocrinology and metabolism; I.F.: 5.44
Paracrine and endocrine roles of insulin-like factor 3
No full textInsulin-like factor 3 (INSL3) is expressed in Leydig cells of the testis and theca cells of the ovary. This peptide affects testicular descent by acting on gubernaculum via its specific receptor leucine-rich repeat-containing G protein-coupled receptor 8 (LGR8). From initial animal data showing the cryptorchid phenotype of Insl3/Lgr8 mutants, an extensive search for mutations in INSL3 and LGR8 genes was undertaken in human patients with cryptorchidism, and a frequency of mutation of 4-5% has been detected. However, definitive proofs of a causative role for some of these mutations are still lacking. More recent data suggest additional paracrine (in the testis and ovary) and endocrine actions of INSL3 in adults. INSL3 circulates at high concentrations in serum of adult males and its production is dependent on the differentiation effect of LH. Therefore, INSL3 is increasingly used as a specific marker of Leydig cell differentiation and function
Role of relaxin in human osteoclastogenesis.
No full textRecently, we have demonstrated that INSL3 is important for bone metabolism, and in this study we analyzed the possible role of the cognate hormone relaxin on human osteoclasts. In fact, previous studies showed an effect of relaxin on peripheral blood mononuclear cells (PBMCs), the precursors of osteoclasts. Analysis of the expression of the relaxin receptor RXFP1 and RLN-2 mRNA in primary cell cultures of human osteoclasts obtained from PBMCs showed by reverse transcriptase PCR and immunofluorescence only the presence of RXFP1 transcripts. Analysis of the in vitro effects of relaxin on osteoclastogenesis showed that relaxin is able alone to induce the differentiation of PBMCs into mature osteoclasts. This study shows, for the first time, that relaxin has an effect on bone metabolism, facilitating the differentiation of osteoclasts. A possible role for relaxin in osteolytic bone metastasis is also proposed
The great opportunity of the andrological patient: cardiovascular and metabolic risk assessment and prevention
No full textAndrologists, cardiologists and diabetologists (and general practitioners) have the great opportunity to collaborate and find shared clinical workup for the benefit of a large number of men. Several evidence established a link between erectile dysfunction (ED), cardiovascular disease (CVD), diabetes, and metabolic syndrome. Not only these conditions share many risk factors and pathophysiological mechanisms but also an emerging paradigm indicates that ED is, in fact, an independent marker of cardiovascular disease risk, CV events and CV mortality. However, there is no consensus on the best cardiologic investigation in men with ED with no known CVD and, on the contrary, on what is the clinical and prognostic role of detecting ED during cardiovascular investigation and CVD risk assessment. Only vasculogenic ED, which represents the most common type of organic ED, indeed represents a harbinger of CVD, especially for younger patients, and might be diagnosed by dynamic penile color doppler ultrasonography, which represents a real cardiovascular imaging technique that give evidence on the presence of systemic endothelial dysfunction and atherosclerosis. Furthermore, assessment of glucose and lipid metabolism is warranted as first step workup in all ED patients, and diabetologists should ask their patients for erectile function, address ED patients to andrologists, and consider vasculogenic ED in the context of the cardiovascular and metabolic workup and in the context of diabetic complications. Sexual symptoms (and testosterone levels) should sound as harbinger for cardiovascular and metabolic investigation and cardiologists and diabetologists have the opportunity to have a symptom (erectile dysfunction) and a vascular test (penile color doppler) that help them in better management of patients, their comorbidities and complications
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