125 research outputs found

    Fatherhood and sperm DNA damage in testicular cancer patients

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    Testicular cancer (TC) is one of the most treatable of all malignancies and the management of the quality of life of these patients is increasingly important, especially with regard to their sexuality and fertility. Survivors must overcome anxiety and fears about reduced fertility and possible pregnancy-related risks as well as health effects in offspring. There is thus a growing awareness of the need for reproductive counseling of cancer survivors. Studies found a high level of sperm DNA damage in TC patients in comparison with healthy, fertile controls, but no significant difference between these patients and infertile patients. Sperm DNA alterations due to cancer treatment persist from 2 to 5 years after the end of the treatment and may be influenced by both the type of therapy and the stage of the disease. Population studies reported a slightly reduced overall fertility of TC survivors and a more frequent use of ART than the general population, with a success rate of around 50%. Paternity after a diagnosis of cancer is an important issue and reproductive potential is becoming a major quality of life factor. Sperm chromatin instability associated with genome instability is the most important reproductive side effect related to the malignancy or its treatment. Studies investigating the magnitude of this damage could have a considerable translational importance in the management of cancer patients, as they could identify the time needed for the germ cell line to repair nuclear damage and thus produce gametes with a reduced risk for the offspring

    Sperm glyceraldehyde 3-phosphate dehydrogenase gene expression in asthenozoospermic spermatozoa

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    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

    Testicular cancer and sperm DNA damage: short- and long-term effects of antineoplastic treatment

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    The aim of this study was to investigate sperm DNA damage induced by chemo- and radiotherapy in patients with testicular cancer to provide data on the extent and persistence of nuclear damage that might affect individual reproductive potential. We evaluated pre- and post-antineoplastic treatment sperm DNA integrity, expressed as DNA Fragmentation Index (DFI), in a large caseload of testicular cancer patients by sperm chromatin structure assay. The mean total DFI for all patients at T0 was 18.0 ± 12.5%. Sperm chromatin profile was markedly impaired at T3 (27.7 ± 17.4%) and T6 (23.2 ± 15.3%), improving considerably at T12 and T24 (14.0 ± 8.9% and 14.4 ± 10.3%). After chemotherapy, we found a marked increase in DFI at T3 and T6 and a significant reduction at T12 and T24 in comparison with the baseline. In contrast, DFI increased at T3 and T6 after radiotherapy but the subsequent reduction was far less marked, reaching baseline values at T12 and T24. Finally, post-treatment DNA damage was not age or histotype dependent, but was more marked in the advanced stage of cancer. In this study, we showed that the chromatin profile may be affected in the months immediately following the end of the treatment, improving after 12-24 months. Our results thus indicate that post-treatment DNA damage is influenced both by the type and intensity of the therapy and by the pathological and clinical stage of the disease. © 2014 American Society of Andrology and European Academy of Andrology

    Exposure to polychlorinated biphenyls and hexachlorobenzene, semen quality and testicular cancer risk

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    PURPOSE: We carried out a case-control study to investigate the possible role of occupational and environmental exposure to endocrine disruptors in the onset of testicular cancer (TC). METHODS: We evaluated 125 TC patients and 103 controls. Seminal fluid examination and organochlorine analysis were performed in all subjects. Cases and controls were also interviewed using a structured questionnaire to collect demographic information, residence, andrological medical history and dietary information. RESULTS: We found that a higher level of reproductive tract birth defects was associated with a higher risk of TC. With regard to diet, cases reported a higher consumption of milk and dairy products than controls. Overall, there was a statistically significant increase in TC risk in cases with detectable values of total polychlorinated organic compounds against controls (14.4 vs. 1.0 %; p < 0.001). TC patients with detectable levels of organochlorines had lower mean semen parameters than those with undetectable levels, although this difference was not statistically significant. CONCLUSION: The International Agency for Research on Cancer recently included dioxin-like polychlorinated biphenyls (PCBs) in Group 1 of known human carcinogens. Our study confirmed and identified various risk factors for testicular cancer: cryptorchidism, consumption of milk and dairy products, parents' occupation and serum concentration of hexachlorobenzene and PCBs and, for the first time, we showed the correlation between semen quality and the serum concentration of these pollutants

    Androgen receptor polymorphisms and testicular cancer risk

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    Testicular cancer (TC) is currently the most common malignant solid tumour in Caucasian males aged 15-39 years. Epidemiological evidence suggests that its onset may be due to an imbalance in the action of steroidal sex hormones and their receptors. A faulty androgen receptor signalling pathway can, in fact, cause various male reproductive disorders. The androgen receptor (AR) gene has two polymorphic segments consisting of CAG and GGC repeats. The length of CAG repeats has been shown to affect the regulation of AR activity. In our study, we used fragment analysis to evaluate the AR gene repeats of 302 TC patients and 322 controls, to establish if there is any association between repeat number and TC. This study of the largest Italian caseload investigated to date highlighted three particularly significant aspects. First, a CAG repeat number of ≥25 may be considered a risk factor for the onset of TC, given its greater frequency in patients in comparison with controls. This difference became significant for the non-seminoma group. Second, men with CAG repeats below 21 or above 24 were found to have a, respectively, 50 and 76% higher risk of TC than those with CAG 21-24, suggesting that these too can be considered a risk factor for TC. Finally, stage II patients were more likely to have a CAG repeat number 24 than stage I patients. © 2014 American Society of Andrology and European Academy of Andrology

    Ambulatorio Oncofertilità: gestione clinica del paziente della Banca del Seme

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    L’oncofertilità rappresenta un nuovo campo della medicina che comprende una rete integrata di specialisti focalizzati a sviluppare metodi e strategie in grado di preservare e/o ripristinare la potenzialità riproduttiva in soggetti che hanno avuto una diagnosi di cancro. L’oncofertilità prevede quindi l’integrazione di una serie di discipline quali l’oncologia, la medicina della riproduzione, la sessuologia clinica, la pediatria e la bioetica. Appaiono pertanto superati i tempi in cui l’unico obiettivo era la cura del tumore senza badare alle ricadute su fertilità, sessualità e, in definitiva, sulla qualità di vita del paziente. L’oncofertilità rappresenta lo sforzo degli specialisti in tale direzione

    4BNT162b2 mRNA COVID-19 vaccine and semen. What do we know?

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    Background The effects of an mRNA COVID-19 vaccine on spermatozoa parameters are not known. The aim of this study was to evaluate the effect of the BNT162b2 mRNA COVID-19 vaccine on human semen, comparing spermatozoa parameters before and after vaccine inoculation. Materials and methods In this single-center prospective study, voluntary subjects who received mRNA vaccines from February to July 2021 were enrolled. The study population included male subjects aged between 18 and 45 years who completed the BNT162b2 mRNA COVID-19 vaccine cycle. All subjects were evaluated before the first dose of vaccine (T0) and after 3 months (T1) with semen analysis and further analysis of seminal plasma, including colorimetric determination of reactive oxygen metabolites (d-ROM test), electrolytes, and interleukin 6 (IL-6) assessment by enzyme-linked immunosorbent assay technology. Results The experimental sample included 47 subjects (age: 29.3 +/- 6.0 years, range 24-32; body mass index: 23.15 +/- 2.5 kg/m(2), range 19.2-28.0). All the subjects reported no systemic side effects. No significant differences were observed in any spermatozoa parameter between T0 and T1. A subanalysis was performed in oligoazoospermic and asthenozoospermic subjects, confirming the same results. Electrolyte analysis also showed no significant differences before and after vaccine inoculation. Finally, no significant differences were observed in T0, compared to T1 for the d-ROM test and IL-6. Discussion and conclusion In this study, no significant differences in spermatozoa parameters before and after vaccine inoculations were found. Furthermore, oxidative stress analysis,, the activity of the cell membrane, and IL-6, as a marker of inflammation, was not affected by the mRNA COVID-19 vaccine. These results suggest that this vaccine is safe for male semen quality

    Effects of endocrine disruptors on fetal testis development, male puberty, and transition age

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    Purpose Endocrine disruptors (EDs) are exogenous substances able to impair endocrine system; consequently, they may cause numerous adverse effects. Over the last years, particular focus has been given to their harmful effects on reproductive system, but very little is known, especially in males. The aim of this review is to discuss the detrimental effects of EDs exposure on fetal testis development, male puberty, and transition age. Methods A search for the existing literature focusing on the impact of EDs on fetal testis development, male puberty, andrological parameters (anogenital distance, penile length, and testicular volume), and testicular cancer with particular regard to pubertal age provided the most current information available for this review. Human evidence-based reports were given priority over animal and in vitro experimental results. Given the paucity of available articles on this subject, all resources were given careful consideration. Results Information about the consequences associated with EDs exposure in the current literature is limited and often conflicting, due to the scarcity of human studies and their heterogeneity. Conclusions We conclude that current evidence does not clarify the impact of EDs on human male reproductive health, although severe harmful effects had been reported in animals. Despite controversial results, overall conclusion points toward a positive association between exposure to EDs and reproductive system damage. Further long-term studies performed on wide number of subjects are necessary in order to identify damaging compounds and remove them from the environment
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