Elena Speltra
University of Padua
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Featured researches published by Elena Speltra.
The Journal of Urology | 2010
Alberto Ferlin; Elena Speltra; Cristina Patassini; Mauro A. Pati; Andrea Garolla; Nicola Caretta; Carlo Foresta
PURPOSE Varicocele may be associated with normozoospermia or oligozoospermia. Much controversy still exists regarding the diagnosis, management and pathophysiology of spermatogenesis alterations associated with varicocele. The increased temperature induced by varicocele and stress in general may activate heat shock proteins and heat shock factors with a protective function in cells. We analyzed the expression of 5 heat shock proteins and heat shock factors in the sperm of men with normozoospermia and oligozoospermia with or without varicocele. MATERIALS AND METHODS We performed a prospective study between June 2008 and February 2009 at an academic clinic in 117 consecutive patients with varicocele and 68 controls without varicocele. Four groups were based on the presence/absence of varicocele and normozoospermia/oligozoospermia. Subjects were studied by history, physical examination, scrotal Doppler ultrasound, semen analysis, reproductive hormone plasma levels and quantitative real-time polymerase chain reaction in RNA extracted from ejaculated sperm to analyze HSP90, HSPA4, HSF1, HSF2 and HSFY expression. RESULTS Increased HSPA4, HSF1 and HSF2 were observed in the sperm of men with varicocele and in those with oligozoospermia. Levels were maximum when the 2 conditions were present. Increased HSP90 was observed in oligozoospermia cases independent of varicocele. HSFY was up-regulated only in patients with varicocele, especially those with normozoospermia. CONCLUSIONS To our knowledge we describe for the first time the expression of different heat shock proteins and heat shock factors in ejaculated sperm. While some of these proteins are up-regulated in men with oligozoospermia and varicocele, HSFY is up-regulated only in the presence of varicocele and especially in men with normozoospermia. This suggests that it may be a molecular marker of an adequate or inadequate response to the damaging effect of varicocele on spermatogenesis.
Journal of Medical Genetics | 2006
Barbara Arredi; Alberto Ferlin; Elena Speltra; Chiara Bedin; Daniela Zuccarello; Francesco Ganz; Eleonora Marchina; Liborio Stuppia; Csilla Krausz; Carlo Foresta
Background: A limited number of studies aimed at investigating the possible association of Y-chromosome haplogroups with microdeletions of the azoospermia factors (AZFs) or with particular infertile phenotypes, but definitive conclusions have not been attained. The main confounding elements in these association studies are the small sample sizes and the lack of homogeneity in the geographical origin of studied populations, affecting, respectively, the statistical power and the haplogroup distribution. Materials and methods: To assess whether some Y-chromosome haplogroups are predisposing to, or protecting against, azoospermia factor c (AZFc; b2/b4) deletions, 31 north Italian patients carrying the AZFc b2/b4 microdeletion were characterised for 8 Y-chromosome haplogroups, and compared with the haplogroup frequency shown by a north Italian population without the microdeletion (n = 93). Results and discussion: A significant difference was observed between the two populations, patients with microdeletions showing a higher frequency of the E haplogroup (29.3% vs 9.7%, p<0.01). The geographical homogeneity of the microdeleted samples and of the control population, controlled at microgeographical level, allows the possibility that the geographical structure of the Y genetic variability has affected our results to be excluded. Conclusion: Thus, it is concluded that in the north Italian population Y-chromosome background affects the occurrence of AZFc b2/b4 deletions.
PLOS ONE | 2013
Cristina Patassini; Andrea Garolla; Alberto Bottacin; Massimo Menegazzo; Elena Speltra; Carlo Foresta; Alberto Ferlin
No valid method is currently available to analyze the entire genome of sperm, including aneuploidies and structural chromosomal alterations. Here we describe the optimization and application of array-Comparative Genomic Hybridization (aCGH) on single human sperm. The aCGH procedure involves screening of the entire chromosome complement by DNA microarray allowing having a molecular karyotype, and it is currently used in research and in diagnostic clinical practice (prenatal diagnosis, pre-implantation genetic diagnosis), but it has never been applied on sperm. DNA from single human sperm isolated by micromanipulator was extracted, decondensed and amplified by whole-genome amplification (WGA) and then labeled, hybridized to BAC array, and scanned by microarray scanner. Application of this protocol to 129 single sperm from normozoospermic donors identified 7.8% of sperm with different genetic anomalies, including aneuploidies and gains and losses in different chromosomes (unbalanced sperm). On the contrary, of 130 single sperm from men affected by Hodgkin lymphoma at the end of three months of chemotherapy cycles 23.8% were unbalanced. Validation of the method also included analysis of 43 sperm from a man with a balanced translocation [46,XY,t(2;12)(p11.2;q24.31)], which showed gains and losses corresponding to the regions involved in the translocation in 18.6% of sperm and alterations in other chromosomes in 16.3% of sperm. Future application of this method might give important information on the biology and pathophysiology of spermatogenesis and sperm chromosome aberrations in normal subjects and in patients at higher risk of producing unbalanced sperm, such as infertile men, carriers of karyotype anomalies, men with advanced age, subjects treated with chemotherapy, and partners of couples with repeated miscarriage and repeated failure during assisted reproduction techniques.
The Journal of Clinical Endocrinology and Metabolism | 2016
Luca De Toni; Andrea Di Nisio; Elena Speltra; Maria Santa Rocca; Marco Ghezzi; Daniela Zuccarello; Nunzio Turiaco; Alberto Ferlin; Carlo Foresta
CONTEXT The G protein-coupled receptor GPRC6A is an emerging effector with multiple endocrine roles, including stimulation of T production from the testis. Recently, two men with an inactivating mutation (F464Y) of GPRC6A have been identified, and they showed primary testicular failure and deranged spermatogenesis. Furthermore, one of them also reported cryptorchidism at birth. In addition, a polymorphism (rs2274911, Pro91Ser) in GPRC6A is associated with prostate cancer, a typical androgen-sensitive cancer. OBJECTIVE To study the possible association between rs2274911 polymorphism and male fertility and/or cryptorchidism. Design, Patients, Settings: A total of 611 subjects, including 343 infertile patients, 197 normozoospermic controls, and 71 cryptorchid newborns, were retrospectively selected. METHODS Sequencing analysis for rs2274911 polymorphism and F464Y mutation, and serum levels of FSH, LH, and T were assessed. In vitro functional studies for rs2274911 and F464Y were also performed. RESULTS Homozygous subjects for the risk allele A of rs2274911 had a 4.60-fold increased risk of oligozoospermia and 3.52-fold increased risk of cryptorchidism. A significant trend for increased levels of LH in the GA and AA genotypes, compared with GG homozygotes, was detected in men with azoospermia/cryptozoospermia (P for trend = .027), further supporting an association with primary testicular failure. The mutation F464Y was found in one cryptorchid child (one in 71; 1.41%). Functional studies showed that the A allele of rs2274911 and the F464Y substitution were associated with lower exposition of the receptor on the cell membrane and a reduced downstream phosphorylation of ERK1/2 with respect to wild type. CONCLUSION Our results suggest that GPRC6A inactivation or sub-function contributes to reduced exposure to androgens, leading to cryptorchidism during fetal life and/or low sperm production in adulthood.
Human Reproduction | 2016
Maria Santa Rocca; Elena Speltra; Massimo Menegazzo; Andrea Garolla; Carlo Foresta; A. Ferlin
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.
Endocrinology | 2015
Andrea Di Nisio; Luca De Toni; Elena Speltra; Maria Santa Rocca; Giuseppe Taglialavoro; Alberto Ferlin; Carlo Foresta
In this study we aimed to elucidate a possible role of T in the regulation of sclerostin, a glycoprotein secreted by osteocytes known to regulate bone mass. To this end, we evaluated the effect of T stimulation on sclerostin production and gene expression in human cultured osteocytes. In addition, we evaluated serum sclerostin levels in a cohort of 20 hypogonadal male patients, compared with 20 age-matched eugonadal controls. Stimulation with DHT decreased sclerostin expression in cultured osteocytes in a time- and dose-dependent manner. Confirming a direct androgen receptor-mediated effect on sclerostin production, flutamide coincubation and silencing of androgen receptor gene in osteocytes abolished the DHT effects. In addition, hypogonadal patients showed higher serum sclerostin levels with respect to controls (145.87 ± 50.83 pg/mL vs 84.02 ± 32.15 pg/mL; P < .001) and in both probands and controls, serum T levels were negatively correlated with sclerostin (R = -0.664, P = 0.007, and R = -0.447, P = .045, respectively). Finally, multiple stepwise regression analysis showed that T represented the only independent predictor of sclerostin levels. In conclusion, by showing a direct correlation between T and sclerostin, both in vivo and in vitro, this study adds further support to the emerging clinical and experimental studies focusing on sclerostin as a therapeutic target for osteoporosis treatment.
Human Reproduction | 2015
Andrea Garolla; Barbara Sartini; Ilaria Cosci; Damiano Pizzol; Marco Ghezzi; Alessandro Bertoldo; Massimo Menegazzo; Elena Speltra; Alberto Ferlin; Carlo Foresta
STUDY QUESTION Is there a difference between molecular karyotype of single sperm selected by high-magnification microscopy from infertile patients with testicular damage and from proven fertile controls? SUMMARY ANSWER The molecular karyotype of single sperm from patients with testiculopathy had a significantly higher percentage of chromosomal alterations than fertile controls. WHAT IS KNOWN ALREADY Infertile patients with testicular impairment have many sperm with aneuploidies and/or increased structural chromosome alterations. In these patients, sperm use by ICSI has poor outcome and raises concerns about the possible impact on pregnancy loss and transmission of genes abnormalities in offspring. High-magnification microscopy has been recently introduced to select morphologically better sperm aimed at improving ICSI outcome. However, there are no studies evaluating the molecular karyotype of sperm selected by this method. STUDY DESIGN, SIZE, DURATION Three consecutive infertile patients with oligozoospermia due to testicular damage and three age-matched proven fertile men attending a tertiary care center, were enrolled in the study from September to November 2014. Inclusion criteria of patients were age ≥30 ≤35 years, at least 2 years of infertility, oligozoospermia (sperm count below 10 million), reduced testicular volumes high FSH plasma levels and absence of altered karyotype, Y chromosome microdeletions, cystic fibrosis transmembrane conductance regulator gene mutations, sperm infections, cigarette smoking, varicocele, obesity. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants were evaluated for sperm parameters, sex hormones and testicular color-doppler ultrasound. From each semen sample, 20 sperm with large vacuoles (LVs), 20 with small vacuoles (SVs) and 20 with no vacuoles (NVs) were retrieved individually by a micromanipulator system. Each cell was further analyzed by whole genome amplification and array comparative genomic hybridization (aCGH). MAIN RESULTS AND THE ROLE OF CHANCE The aCGH allowed us to detect chromosomal aneuploidies, unbalanced translocations and complex abnormalities. Sperm selected from infertile patients showed a higher percentage of abnormal molecular karyotypes than controls (19.4 versus 7.7%, respectively, P < 0.001). In particular, sperm with LV and SV showed 38.3 and 20.0% abnormal karyotype in infertile men versus 18.3 and 5.0% in controls, respectively (both P < 0.01). Complex abnormalities were found only in the LV category. An abnormal karyotype was never found in NV sperm from both patients and controls. LIMITATIONS REASONS FOR CAUTION The main limitation of this study is the low number of included subjects. Moreover, a time of writing we have no data regarding the ICSI outcome using LV, SV or NV sperm. This is the first study evaluating the molecular karyotype of single sperm selected by high-magnification microscopy and further confirmation of the data is needed. WIDER IMPLICATIONS OF THE FINDINGS Our data showed that sperm from infertile patients with testicular impairment have a higher percentage of abnormal molecular karyotypes than sperm from fertile controls. Therefore, if confirmed, our data suggest that the use of individually retrieved NV sperm may improve ICSI outcome in infertile men with testicular damage.
The Journal of Clinical Endocrinology and Metabolism | 2007
Alberto Ferlin; Barbara Arredi; Elena Speltra; Carla Cazzadore; Riccardo Selice; Andrea Garolla; Andrea Lenzi; Carlo Foresta
Journal of Endocrinological Investigation | 2016
A. Di Nisio; L. De Toni; Marco Ferigo; Maria Santa Rocca; Elena Speltra; A. Ferlin; Carlo Foresta
Molecular Human Reproduction | 2007
Alberto Ferlin; Elena Speltra; Andrea Garolla; Riccardo Selice; Daniela Zuccarello; Carlo Foresta