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Biomedical subjects

A Garolla

Publications and source records attributed to A Garolla.

At least 19 recordsLinked to original sources
PubMed2006

Cryptozoospermia with normal testicular function after allogeneic stem cell transplantation: a case report.

One of the most frequent consequences of allogeneic haemopoietic stem cell transplantation (allo-SCT) in both males and females is gonadal insufficiency. We report the case of a 27-year-old myelodysplastic male who developed azoospermia after allogeneic transplantation of haemopoietic stem cells from his HLA-identical sister. Post-transplant azoospermia was alternated with intermittent severe oligospermia. The patient had a normal endocrine pattern and evidence of mild chronic graft-versus-host disease (cGVHD). Normal intratesticular spermatogenesis was revealed by bilateral fine needle aspiration (FNA) cytology. Inflammation was evident at semen analysis, but no infection was detected by microbiological examination and sperm culture. These findings, together with the re-appearance of sperm cells at semen analysis after a low-dose immunosuppressive treatment, suggested the presence of cGVHD of the urogenital tract, causing a reversible obstruction of the spermatic tract and cryptozoospermia. This is the first case report documenting a severe impairment of sperm count because of a reversible obstruction of the seminal tract, likely caused by cGVHD, in a long-term survivor of allo-SCT with normal endocrine pattern. An important practical consequence of this case report is the fact that azoospermia was cured using low-dose immunosuppressive therapy, and this allowed us to avoid expensive stimulatory treatments with gonadotrophins, which remain, however, ineffective if the obstruction of spermatic tracts is not removed. A spontaneous uncomplicated pregnancy occurred in the partner of the patient 3 months after the corticosteroid treatment withdrawal.

Adult↗
PubMed2006

Reduced number of circulating endothelial progenitor cells in hypogonadal men.

CONTEXT: Endothelial dysfunction seems to be the first step of the atherosclerotic process. In the past few years, it has been demonstrated that injured endothelial monolayer is restored by a premature pool of circulating progenitor cells (PCs) and a more mature one of circulating endothelial PCs (EPCs). Even though there is increasing evidence that estrogens play a beneficial role on EPCs and, even if debated, on the cardiovascular system, less is known about androgens. OBJECTIVE: Our objective was to evaluate the levels of circulating PCs and EPCs in men with hypogonadotropic hypogonadism (HH) and the effect of prolonged testosterone (T) replacement therapy on these cells. DESIGN AND SETTING: We conducted a prospective study on males with HH at a university andrological center. PATIENTS: The study included 10 young HH patients (28.6 +/- 3.1 yr) and 25 age-matched controls. INTERVENTIONS: Idiopathic HH patients were treated with T gel therapy, 50 mg/d for 6 months. MAIN OUTCOME MEASURES: We assessed circulating PC and EPC concentrations and immunocytochemistry for androgen receptor expression on cultured EPCs. RESULTS: At baseline, HH patients showed a significant reduction of both PCs and EPCs with respect to controls. T replacement therapy induced a significant increase of these cells with respect to baseline. Immunocytochemistry on cultured EPCs showed strong expression of the androgen receptor. CONCLUSIONS: Hypotestosteronemia is associated with a low number of circulating PCs and EPCs in young HH subjects. T treatment is able to induce an increase in these cells through a possible direct effect on the bone marrow.

Adult↗
PubMed2005

Resumption of spontaneous erections in selected patients affected by erectile dysfunction and various degrees of carotid wall alteration: role of tadalafil.

OBJECTIVE: To evaluate the possible improvement of sexual activity following a non on-demand administration of a long half-life selective inhibitor of phosphodiesterase type 5 (PDE-5) in elderly patients without major cardiovascular risk factors. METHODS: Sixty subjects with erectile dysfunction (ED) aged 60-70 years and 30 control patients aged 18-40 years, affected by psychogenic ED, were studied. All underwent routine and hormonal blood tests, Nocturnal Penile Tumescence Rigidity Monitoring test (NPTRM), ultrasonographyc evaluation of common carotid artery intima-media thickness (IMT) and penile colour Doppler ultrasonography (P-CDU). All patients underwent therapy with tadalafil 20 mg in alternative days, non on-demand, at 5.00 p.m., for three consecutive months. IIEF-5, NPTRM test and P-CDU were re-evaluated one month after the end of the therapy. RESULTS: Among elderly subjects 20 (33%) had normal carotid IMT (< 0.9 mm), 15 (25%) minimal increase of carotid thickness (IMT = 0.9-1.2 mm) and 25 (42%) one or more carotid plaques (IMT > 1.3 mm). NPTRM and P-CDU parameters were inversely related to different degrees of carotid wall alteration and showed a significant improvement respect to pre-treatment only in patients without atherosclerotic plaques. Also IIEF-5 showed significant improvements only in patients without atherosclerotic plaques. CONCLUSIONS: In elderly subjects with slight or no signs of vascular disease at the carotid level, chronic and non on-demand treatment with tadalafil can induce spontaneous resumption of erections, probably through the improvement of endothelial function, but direct evidences to confirm this hypothesis are required.

Adolescent↗
PubMed2005

Diagnosing erectile dysfunction: flow-chart.

Erectile dysfunction (ED) has been defined by the National Institute of Health (NIH) as the inability to achieve and/or maintain an erection for a satisfactory sexual intercourse. Discordant data have been reported on ED epidemiology with prevalence ranging from 12% to 52%. A recent study reported an ED prevalence of 12.8% in Italy. ED is a symptom, sometimes the first, of different internal diseases. ED can mark the point where evaluation and prevention of important diseases (such as diabetes, arterial hypertension, atherosclerosis) hitherto unknown by the patients, can begin. The andrologist's cultural baggage must include the ability to identify the pathology that can determine ED and the capacity to programme a specific diagnostic workup.

Algorithms↗
PubMed2005

Association of partial AZFc region deletions with spermatogenic impairment and male infertility.

BACKGROUND: Complete deletions of the AZFc region in distal Yq are the most frequent molecular genetic cause of severe male infertility. They are caused by intrachromosomal homologous recombination between amplicons--large, nearly identical repeats--and are found in 5-10% of cases of azoospermia and severe oligozoospermia. Homologous recombination may also generate different partial deletions of AZFc, but their contribution to spermatogenic impairment has not been confirmed. METHODS: In this study we analysed the prevalence and characteristics of different partial AZFc deletions and their association with spermatogenic failure. We studied 337 infertile men with different spermatogenic impairment and 263 normozoospermic fertile men using AZFc specific sequence tagged site markers and DAZ specific single nucleotide variants. RESULTS: We identified 18 cases of partial AZFc deletions in the infertile group (5.3%) and one case in the control group (0.4%). Seventeen deletions had the "gr/gr" pattern, one the "b2/b3" pattern, and one represented a novel deletion with breakpoints in b3 and b4 amplicons. Partial AZFc deletions were associated with different spermatogenic phenotypes ranging from complete azoospermia to only moderate oligozoospermia. CONCLUSIONS: Together with published data, our analysis of DAZ gene copy suggested that the contribution of the different deletions to male infertility varies: only partial AZFc deletions removing DAZ1/DAZ2 seem to be associated with spermatogenic impairment, whereas those removing DAZ3/DAZ4 may have no or little effect on fertility. These data show that, beside complete AZFc deletions, specific partial deletions represent a risk factor for male infertility, even if with different effect on spermatogenesis.

Adult↗
PubMed2005

Chromosome abnormalities in sperm of individuals with constitutional sex chromosomal abnormalities.

The most common type of karyotype abnormality detected in infertile subjects is represented by Klinefelter's syndrome, and the most frequent non-chromosomal alteration is represented by Y chromosome long arm microdeletions. Here we report our experience and a review of the literature on sperm sex chromosome aneuploidies in these two conditions. Non mosaic 47,XXY Klinefelter patients (12 subjects) show a significantly lower percentage of normal Y-bearing sperm and slightly higher percentage of normal X-bearing sperm. Consistent with the hypothesis that 47,XXY germ cells may undergo and complete meiosis, aneuploidy rate for XX- and XY-disomies is also increased with respect to controls, whereas the percentage of YY-disomies is normal. Aneuploidy rates in men with mosaic 47,XXY/46,XY (11 subjects) are lower than those observed in men with non-mosaic Klinefelter's syndrome, and only the frequency of XY-disomic sperm is significantly higher with respect to controls. Although the great majority of children born by intracytoplasmic sperm injection from Klinefelter subjects are chromosomally normal, the risk of producing offspring with chromosome aneuploidies is significant. Men with Y chromosome microdeletions (14 subjects) showed a reduction of normal Y-bearing sperm, and an increase in nullisomic and XY-disomic sperm, suggesting an instability of the deleted Y chromosome causing its loss in germ cells, and meiotic alterations leading to XY non-disjunction. Intracytoplasmic injection of sperm from Y-deleted men will therefore transmit the deletion to male children, and therefore the spermatogenic impairment, but raises also concerns of generating 45,X and 47,XXY embryos.

Chromosome Aberrations↗
PubMed2005

Molecular analysis of the androgen receptor gene in testicular cancer.

Testicular cancer (TC) is the most common solid tumour in white males aged 20-34 years, and its incidence has doubled over the past 40 years. Some risk factors for TC have been proposed, such as cryptorchidism, infertility and testicular dysgenesis. However, the causes of TC remain still largely unknown. Recently a genetic basis for TC has been proposed, but specific genetic alterations have not been identified. The risk of TC is markedly increased in subjects with androgen insensitivity and some authors have suggested that mutations in the androgen receptor (AR) gene or disorders of CAG and GGC repeats could be related to TC. However, definitive data have not been produced. In this study, we analysed the AR gene for mutations and CAG and GGC triplets in exon 1 in 123 patients affected by TC. In three patients (2.3%) we found a mutation in the AR gene, two of which represent a novel mutation. Evaluation of CAG and GGC repeat numbers showed no difference with respect to controls when these variables were analysed separately. However, when joint distributions of CAG and GGC were considered, we found that the combination CAG=20/GGC=17 was significantly more frequent in TC patients (8.1%) with respect to controls (1.7%, P<0.05). Furthermore, we observed that in TC subjects, differently from controls, the joint analysis of CAG and GGC showed a statistically significant dependence among these variable repeats. In conclusion, our data show for the first time a high prevalence of AR gene mutations in patients affected by TC and suggest that some CAG/GGC combinations might be more frequently associated with an increased risk of TC.

Adult↗
PubMed2004

Lack of the T54A polymorphism of the DAZL gene in infertile Italian patients.

The 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.

Ethnicity↗
PubMed2004

Androgen receptor gene CAG and GGC repeat lengths in idiopathic male infertility.

The androgen receptor (AR) has two polymorphic sites in exon 1, characterized by different numbers of CAG and GGC repeats resulting in variable lengths of polyglutamine and polyglycine stretches. Longer CAG repeats result in a reduced AR transcriptional activity, whereas the role of the GGC triplets is less clear. A relationship between decreased spermatogenesis and moderate expansion in the CAG tract has been found in some studies, but not in others. Furthermore, the joint distribution of CAG and GGC repeats in male infertility has never been reported before. We analysed CAG and GGC repeat lengths in a group of 163 men with idiopathic infertility compared with 115 fertile normozoospermic men. No difference was found between patients and controls in the mean and median values, and in distribution of CAG and GGC, when considered separately. However, the analysis of the joint distribution of CAG and GGC showed that the distribution of particular haplotypes is significantly different between patients and controls. In particular, two CAG/GGC haplotypes seem to increase susceptibility to infertility (CAG = 21/GGC = 18 and CAG >/=21/GGC >/=18, relative risk 2.47 and 1.6), while one haplotype (CAG >/=23/GGC </=16, relative risk 0.09) seems to confer a protective effect against the disease. These data show a combined effect of CAG and GGC repeat numbers on AR function and the first evidence of a relationship of particular CAG/GGC haplotypes with male infertility.

Base Sequence↗
PubMed2004

Role of androgens in erectile function.

PURPOSE: Erectile response in mammals is centrally and peripherally regulated by androgens. Severe hypogonadism in men usually results in loss of libido and potency. The present studies were designed to evaluate the possible influence of circulating androgens in the regulation of sexual function. MATERIALS AND METHODS: A total of 15 men with severe hypogonadism (testosterone less than 2.0 ng/ml) were recruited. The control group consisted of 20 patients with psychogenic erectile dysfunction. All subjects underwent nocturnal penile tumescence (NPT) and rigidity monitoring during 2 consecutive nights, evaluation of cavernous artery flow using penile color duplex ultrasound (P-CDU), and real-time visually stimulated erection evaluation at baseline and after administration of 50 mg sildenafil or 3 mg apomorphine. NPT, P-CDU and visually stimulated erection were evaluated after 6 months of therapy with a 5 mg daily testosterone patch. RESULTS: NPT analysis in subjects with severe hypogonadism showed a significant decrease in sleep related erections. P-CDU showed a partial erectile response with an alteration of the parameters analyzed, and the visually stimulated erections test was pathological. Administration of 3 mg apomorphine and 50 mg sildenafil has no influence on erectile function. Testosterone treatment for 6 months induced normalization of NPT and P-CDU parameters, and of visually stimulated erection effects with the restoration of a normal response to pharmacological stimulation with apomorphine or sildenafil. CONCLUSIONS: Our results show that testosterone has a key role in the central and peripheral modulation of erectile function even if the accurate testosterone plasma level threshold that may influence these processes remains to be established.

Adult↗
PubMed2003

Erectile function in elderly: role of androgens.

Erectile function progressively declines with age, although most old men's erectile rigidity remains adequate for vaginal intercourses. Recently it has been demonstrated that a significant proportion of men over 60 years of age has a biochemical hypogonadism (defined as below the 2.5th percentile for young men). It is generally accepted that erectile response in mammals is regulated by androgens both centrally and peripherically, but in male ageing a casual relationship between androgen levels and erectile function has not been established yet. The present study was designed to evaluate the possible relationships between circulating androgens and sexual activity in a group of healthy old men without erectile dysfunction. Forty men with a mean age of 68 +/- 6 years (range 61-75 years) were recruited among healthy subjects undergoing periodic health screening. The control group consisted of 30 young volunteers with a mean age of 33 +/- 5 years (range 26-40 years). These subjects had good general health and stable relationship with at least one successful intercourse for week. All subjects performed: 1) hormonal assessment (total testosterone, free testosterone, DHT, FSH and LH); 2) nocturnal penile tumescence monitoring during two consecutive nights. The findings of this study show a significant decrease in frequency, duration and degree of nocturnal erectile episodes in old men with respect to those observed in young controls. The alteration of these parameters was more evident in old subject showing a reduction of testosterone plasma levels. In hypotestosteronemic subjects DHT treatment significantly improved nocturnal penile tumescence parameters even if these still differed from those of controls (p<0.001). On the basis of these observations we hypothesize that hypoandrogenism in old men, also in presence of normal sexual activity, may influence locally the erectile mechanisms. However hypoandrogenism, associated to other conditions negatively influencing the erectile activity, may be an important co-factor in the induction of erectile dysfunction in aging.

Adult↗
PubMed2001

Different insulin-like 3 (INSL3) gene mutations not associated with human cryptorchidism.

Cryptorchidism is the most frequent congenital anomaly of the urogenital tract in the male, but its etiology is for the most part unknown. Evidence suggests that a possible genetic cause may be involved. Animal models support this hypothesis, and in particular INSL3 (Leydig insulin-like 3 hormone) has been proposed as putative gene for cryptorchidism, since male mice mutant for Insl3 exhibit bilateral abdominal cryptorchidism due to alteration of gubernaculum development. In this study, we analyzed whether mutations in INSL3 could be associated with human cryptorchidism. Heteroduplex analysis and sequencing of both exons of INSL3 in 65 ex-cryptorchid patients and a group of control subjects allowed us to find four nucleotide changes in the sequence of exon I. These mutations are all single base substitutions from G to A at position 27, 96, 126 and 178. Only the 178G-->A substitution changes codon 60 from alanine to threonine (A60T). All mutations were found in comparable distribution in ex-cryptorchid patients and non-cryptorchid men. Therefore, all mutations represent neutral polymorphisms not associated with phenotype. This study confirms previous observations and demonstrates a novel polymorphism in the INSL3 gene. In contrast to that described for the mutant mouse, these data indicate that mutations of INSL3 do not seem to represent a frequent cause of cryptorchidism.

Adult↗
PubMed2001

Store-operated calcium influx and stimulation of steroidogenesis in rat Leydig cells: role of Ca(2+)-activated K(+) channels.

This study evaluates the role of internal calcium store depletion in the activation of ionic fluxes and steroidogenesis in adult rat Leydig cells. Thapsigargin and cyclopiazonic acid, two inhibitors of Ca(2+)-adenosine triphosphatase of internal Ca(2+) stores induced a dose-dependent rise in intracellular Ca(2+) concentrations following kinetics that would not be expected if the calcium rise was dependent only on internal calcium store depletion, but it was in keeping with the presence of calcium influx from the external medium. In fact, chelation of external calcium with EGTA during the plateau phase reduced the intracellular calcium concentration to basal levels. When added in calcium-free medium, thapsigargin and cyclopiazonic acid still induced a rise in the intracellular calcium concentration that was transient, and when calcium was added back to the medium, a rapid and sustained intracellular calcium increase was observed. Thapsigargin and cyclopiazonic acid induced a dose-dependent rise in testosterone secretion in the presence and absence of calcium in the external medium, although in calcium-free medium this stimulatory effect was lower. Leydig cell plasma membrane potential monitoring demonstrated that thapsigargin and cyclopiazonic acid induced first a rapid hyperpolarization, followed by a sustained depolarization phase that was reversed by the addition of the calcium-chelating agent EGTA. In the absence of calcium in the external medium the first phase of hyperpolarization was still present, but it was not followed by plasma membrane depolarization but by the slow return of plasma membrane potential to resting levels. The readdition of calcium to the external medium induced the rapid plasma membrane depolarization. Plasma membrane hyperpolarization was completely abolished by Leydig cell preincubation with the K(+) channel blockers tetraethylammonium and charybdotoxin. Leydig cell preincubation with K(+) channel inhibitors reduced the thapsigargin-stimulated Ca(2+) influx from the external medium and testosterone secretion. These results suggest that internal Ca(2+) stores depletion in rat Leydig cells induces a rise in intracellular Ca(2+), determining important plasma membrane potential variations that influence testosterone secretion.

Animals↗
PubMed2000

Y chromosome microdeletions in infertile men with varicocele.

The pathogenic mechanisms by which varicocele disrupt spermatogenesis are not clearly understood and it is possible that when varicocele is associated with a severe bilateral testiculopathy, other causes may represent the actual aetiological factor. Since microdeletions in the Y chromosome long arm (Yq) have become in last years a major cause of male infertility, we perform a Yq microdeletion screening in infertile men with varicocele. We selected 40 patients with severe oligozoospermia (sperm count<5x10(6)/ml, group 1) and 80 with varicocele and mild oligozoospermia (sperm count 10-20x10(6)/ml, group 2). Deletions of Yq was observed in seven out of 40 patients (17.5%) of group 1, while no deletions were found in patients of group 2, suggesting that the bilateral testicular damage observed in patients of group 1 is due to the underlying genetic anomaly, and not to varicocele itself. The finding of a genetic aetiology in infertile men with varicocele suggests that in such patients a Yq microdeletion screening should be performed, both for a proper diagnosis and to avoid unnecessary treatments that will probably not improve the sperm count.

Biopsy, Needle↗
PubMed2000

FSH in the treatment of oligozoospermia.

The aim of this study was to individuate parameters able to distinguish oligozoospermic subjects who will respond to follicle-stimulating hormone (FSH) therapy. A group of 135 oligozoospermic subjects was divided in three groups considering basal FSH and inhibin B concentrations: group A (normal FSH and inhibin B) characterized by moderate hypospermatogenesis sometimes associated to partial spermatidic arrest; group B (high FSH and normal inhibin B) characterized by hypospermatogenesis associated or not to spermatogonial/spermatocytic arrest; group C (high FSH and low inhibin B) characterized by severe hypospermatogenesis. Seventy-eight patients were treated with FSH at the dose of 75 IU on alternate days while 57 were treated with the same dose every day for 3 months. After FSH treatment a significant increase in ejaculated sperm concentration was observed only in oligozoospermic subjects with normal basal FSH and inhibin B plasma levels (group A) showing a testicular cytological picture of moderate hypospermatogenesis. In these subjects no differences in sperm production were observed between the two protocols of therapy. In the remaining patients of group A, characterized by hypospermatogenesis associated with maturation arrest at spermatidic level and in group B and C, no increase in sperm concentration was observed after therapy. These data suggest that FSH treatment may have a role in oligozoospermic subjects only when the spermatogenetic alterations consist in germ cell depopulation without maturative disturbances and with normal FSH concentrations.

Adult↗
PubMed2000

Role of the AZFa candidate genes in male infertility.

The AZFa region on the Y-chromosome long arm has been recently assembled in a complete sequence map contained in a contig and shown to span more than 1 Mb. It contains three genes, USP9Y, DBY and UTY, but only the former two can be at present considered candidate genes for the infertile phenotype associated with deletion of this interval. These genes have X-homologues and are expressed in many tissues, even if DBY has a shorter transcript expressed in the testis only, strengthening its role in spermatogenesis. Only few patients with gene-specific deletion have been reported and a clear genotype-phenotype relation is still lacking. While deletions or even smaller mutations in USP9Y seem to be associated with a testicular phenotype of severe hypospermatogenesis, patients with deletions of DBY may present both Sertoli cell-only syndrome and severe hypospermatogenesis. On the contrary, the phenotype of patients with deletion of both USP9Y and DBY seem to be invariably azoospermia with a testicular histology of Sertoli cell-only.

Chromosome Mapping↗
PubMed2000

Effects of cryopreservation on progesterone-induced ion fluxes and acrosome reaction in human spermatozoa.

The present study evaluated the effects of cryopreservation on progesterone-induced variations of calcium ion concentration [Ca(2+)](i), plasma membrane potential and acrosome reaction in human spermatozoa. Spermatozoa from 10 fertile donors were divided in two equivalent aliquots, one used as control (fresh spermatozoa) and the other used after freezing-thawing. Measurement of spermatozoa [Ca(2+)](i) before and after freezing-thawing showed a significant reduction of basal [Ca(2+)](i) in thawed spermatozoa (P < 0.01). Progesterone induced a rise of [Ca(2+)](i) both in fresh and thawed spermatozoa with a significant reduction after freezing-thawing (P < 0.01). The monitoring of sperm plasma membrane potential demonstrated that progesterone induced plasma membrane depolarization in fresh spermatozoa that was absent in thawed spermatozoa. The inhibitory effects of freezing-thawing on progesterone induced [Ca(2+)](i) and plasma membrane potential variations in human spermatozoa were closely related to the inhibition of the acrosome reaction. In conclusion the present study demonstrates that freezing-thawing procedures reduce the responsiveness of human spermatozoa to progesterone in terms of [Ca(2+)](i) rise and completely inhibit its effects on plasma membrane potential variations, thus supporting the hypothesis that freezing-thawing procedures may differently modify the plasma membrane receptors for progesterone in human spermatozoa which are known to express at least two receptors for this steroid in their plasma membrane.

Acrosome Reaction↗