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International Journal of Molecular... Dec 2022The real impact of nanoparticles on male fertility is evaluated after a careful analysis of the available literature. The first part reviews animal models to understand... (Review)
Review
The real impact of nanoparticles on male fertility is evaluated after a careful analysis of the available literature. The first part reviews animal models to understand the testicular biodistribution and biopersistence of nanoparticles, while the second part evaluates their in vitro and in vivo biotoxicity. Our main findings suggest that nanoparticles are generally able to reach the testicle in small quantities where they persist for several months, regardless of the route of exposure. However, there is not enough evidence that they can cross the blood-testis barrier. Of note, the majority of nanoparticles have low direct toxicity to the testis, but there are indications that some might act as endocrine disruptors. Overall, the impact on spermatogenesis in adults is generally weak and reversible, but exceptions exist and merit increased attention. Finally, we comment on several methodological or analytical biases which have led some studies to exaggerate the reprotoxicity of nanoparticles. In the future, rigorous clinical studies in tandem with mechanistic studies are needed to elucidate the real risk posed by nanoparticles on male fertility.
Topics: Animals; Male; Tissue Distribution; Testis; Spermatogenesis; Nanoparticles; Fertility
PubMed: 36614018
DOI: 10.3390/ijms24010576 -
Romanian Journal of Morphology and... 2022The appearance of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a major obstacle for the...
The appearance of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a major obstacle for the performing of current medical activities throughout the world. COVID-19 has affected humanity in many ways, thus causing a great medical, social, economic, and political instability. The aim of this study was to make an analysis of the scientific data obtained by so far to highlight the impact that COVID-19 has had on fertility and assisted reproductive technology (ART). Infection with SARS-CoV-2 alters the normal immune response by local and systemic damage to tissues and organs. After the virus enters the body, the first lesions are produced in the respiratory tract. Extrapulmonary lesions specific to COVID-19 include acute renal lesions/acute kidney damage, hepatocellular lesions, neurological diseases, myocardial dysfunction and arrhythmia, gastrointestinal diseases but also genital impairment. The possible impairment of the male reproductive system is because angiotensin-converting enzyme 2 (ACE2) receptors are in an increased number in the testes, seminiferous duct cells, spermatogonia, Leydig cells and Sertoli cells. Many published studies to date have pointed out that COVID-19 could also affect female fertility and disrupt the functions of the female reproductive system. The theory that this virus can also be transmitted sexually and can cause infertility or testicular damage is supported by the fact that the virus can be isolated in the semen of COVID-19 patients but only during the disease. Choosing the best method of treating infertility during the COVID-19 pandemic is multifactorial, but the risk of infection and compliance with specific ART hygiene protocols must always be considered. Currently, there is no scientific basis regarding the fact that the COVID-19 vaccination would influence fertility.
Topics: Humans; Male; Female; COVID-19; SARS-CoV-2; Pandemics; COVID-19 Vaccines; Peptidyl-Dipeptidase A; Fertility; Infertility
PubMed: 36588488
DOI: 10.47162/RJME.63.3.04 -
Human Reproduction Update Mar 2023Increasing childhood cancer survival rates in recent decades have led to an increased focus on fertility as a long-term complication of cancer treatment. Male childhood...
BACKGROUND
Increasing childhood cancer survival rates in recent decades have led to an increased focus on fertility as a long-term complication of cancer treatment. Male childhood cancer survivors often face compromised testicular function as a late effect of chemotherapy exposure, with no well-established options to prevent such damage and subsequent infertility. Despite vincristine being considered to be associated with low-gonadotoxic potential, in prepubertal rodents, it was recently shown to result in morphological alterations of the testis and in severely impaired fertility.
OBJECTIVE AND RATIONALE
This systematic review aimed to evaluate the effects of vincristine-containing regimens on human prepubertal testis with reference to testicular function and fertility in adulthood.
SEARCH METHODS
The systematic search of the literature was conducted according to PRISMA guidelines, and the study was registered with PROSPERO. PubMed and Scopus were searched for articles published in English between 01 January 1900 and 05 March 2021, with the search including 'chemotherapy', 'vincristine', 'prepubertal', 'testis', 'spermatogenesis' and related terms. Abstracts and full-text articles were screened and selected for, providing they met the inclusion criteria (≤12 years at treatment, exposure to vincristine-containing regimens and long-term fertility outcomes). Additional studies were identified via bibliography screening. Bias evaluation across included studies was conducted using the ROBINS-I tool, subdivided into assessment for confounding, participant selection, intervention classification, missing data, outcome measurements and selection of reported results.
OUTCOMES
Our initial search identified 288 articles of which 24 (8%; n = 7134 males) met all inclusion criteria. Control groups were included for 9/24 (38%) studies and 4/24 (17%) studies provided sub-analysis of the relative gonadotoxicity of vincristine-based agents. Primary outcome measures were: fertility and parenthood; semen analysis (World Health Organization criteria); and hormonal function and testicular volume. For the studies that performed vincristine sub-analysis, none reported negative associations with vincristine for the potential of siring a pregnancy, including the largest (n = 6224; hazard ratio = 0.56) controlled study. For semen analysis, no significant difference versus healthy controls was illustrated for mitotic inhibitors (including vincristine) following sub-analysis in one study (n = 143). For hormone analysis, a single study did not find significant impacts on spermatogenesis attributed to vincristine based on levels of FSH and semen analysis, which meant that its administration was unlikely to be responsible for the diminished testicular reserve; however, most of the studies were based on low numbers of patients receiving vincristine-containing chemotherapy. Analysis of bias demonstrated that studies which included vincristine exposure sub-analysis had a lower risk of bias when compared with cohorts which did not.
WIDER IMPLICATIONS
In contrast to recent findings in rodent studies, the limited number of clinical studies do not indicate gonadotoxic effects of vincristine following prepubertal exposure. However, given the relative lack of data from studies with vincristine sub-analysis, experimental studies involving vincristine exposure using human testicular tissues are warranted. Results from such studies could better inform paediatric cancer patients about their future fertility and eligibility for fertility preservation before initiation of treatment.
Topics: Pregnancy; Female; Humans; Male; Child; Vincristine; Neoplasms; Testis; Spermatogenesis; Fertility Preservation
PubMed: 36495566
DOI: 10.1093/humupd/dmac039 -
Environmental Research Feb 2023Endocrine disrupting chemicals (EDCs) are exogenous substances recognised as relevant tumourigenic chemicals. Studies show that even EDCs which were long abolished are... (Review)
Review
INTRODUCTION
Endocrine disrupting chemicals (EDCs) are exogenous substances recognised as relevant tumourigenic chemicals. Studies show that even EDCs which were long abolished are still contributing to the increasing incidence of neoplasia.
AIM
To investigate the association between human exposure to EDCs and the risk of endocrine-related tumours: breast, prostate, thyroid, uterus, testis, and ovary.
METHODS
A systematic review using PubMed, Scopus, and Embase was conducted, searching for original observational studies published between 1980 and 2020, approaching EDCs exposure and endocrine tumourigenic risk in humans. We comprised neoplasia of six endocrine organs. We included all the studies on EDCs reporting tumour odds ratio, risk ratio, or hazard ratio. Study levels of confidence and risk of bias were accessed applying accredited guidelines. Human-made accidents and natural EDCs were not considered in the present study.
RESULTS
Our search returned 3271 papers. After duplicate removal and screening, only 237 papers were included (corresponding to 268 records). EDCs were grouped from the most frequently (pesticides) to the least frequently studied (salts). The most tumourigenic EDC groups were phthalates (63%), heavy metals (54%), particulate matter (47%), and pesticides (46%). Pesticides group comprised the highest number of retrieved studies (n = 133). Increased neoplasia risk was found in 43-67% of the studies, with a lower value for ovary (43%) and a higher value for thyroid (67%).
CONCLUSIONS
The innovative nature of our review comes from including human studies of six endocrine-related neoplasia aiming to understand the contribution of specific EDCs groups to each organ's tumourigenesis. Thyroid was the organ presenting the highest cancer risk after EDC exposure which may explain the increasing thyroid cancer incidence. However, detailed and controlled works reporting the effects of EDCs are scarce, probably justifying conflicting results. Multinational and multicentric human studies with biochemical analysis are needed to achieve stronger and concordant evidence.
Topics: Male; Female; Humans; Endocrine Disruptors; Endocrine System; Pesticides; Testis; Metals, Heavy
PubMed: 36460069
DOI: 10.1016/j.envres.2022.114869 -
European Urology Focus May 2023Guidelines recommend primary retroperitoneal lymph node dissection (RPLND) as a treatment option for tumour marker-negative stage II nonseminomatous germ cell tumour... (Review)
Review
CONTEXT
Guidelines recommend primary retroperitoneal lymph node dissection (RPLND) as a treatment option for tumour marker-negative stage II nonseminomatous germ cell tumour (NSGCT).
OBJECTIVE
To review the literature on oncological outcomes for men with stage II NSGCT treated with RPLND.
EVIDENCE ACQUISITION
A systematic review of studies describing clinicopathological outcomes following primary RPLND in stage II NSGCT was conducted in the MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews databases according to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. Baseline data, perioperative and postoperative parameters, and oncological outcomes were collected.
EVIDENCE SYNTHESIS
In total, 12 of 4387 studies were included, from which we collected data for 835 men. Among men with clinical stage II NSGCT, pathological stage II was confirmed in 615 of 790 patients (78%). Most studies administered adjuvant chemotherapy in cases with large lymph nodes, multiple affected lymph nodes, or persistently elevated tumour markers. Recurrence was observed in 12-40% of patients without adjuvant chemotherapy and 0-4% of patients who received adjuvant chemotherapy.
CONCLUSIONS
The literature describing RPLND in clinical stage II NSGCT is heterogeneous and no meta-analysis was possible, but RPLND can provide accurate staging and may be curative in selected patients.
PATIENT SUMMARY
We reviewed the literature to summarise results after surgical removal of enlarged lymph nodes in the back of the abdomen in men with testis cancer. This procedure provides accurate information on how far the cancer has spread and may provide a cure in selected patients.
Topics: Humans; Male; Lymph Node Excision; Meta-Analysis as Topic; Neoplasm Staging; Testicular Neoplasms; Treatment Outcome
PubMed: 36379869
DOI: 10.1016/j.euf.2022.11.003 -
Medicina (Kaunas, Lithuania) Oct 2022Background and Objectives: During the coronavirus disease 2019 (COVID-19) outbreak, the European Association of Urology (EAU) Guidelines Office Rapid Reaction Group... (Meta-Analysis)
Meta-Analysis Review
Surveillance versus Adjuvant Treatment with Chemotherapy or Radiotherapy for Stage I Seminoma: A Systematic Review and Meta-Analysis According to EAU COVID-19 Recommendations.
Background and Objectives: During the coronavirus disease 2019 (COVID-19) outbreak, the European Association of Urology (EAU) Guidelines Office Rapid Reaction Group (GORRG) recommended that patients with clinical stage I (CSI) seminoma be offered active surveillance (AS). This meta-analysis aimed to evaluate the efficacy of AS versus adjuvant treatment with chemotherapy or radiotherapy for improving the overall survival (OS) of CSI seminoma patients. Materials and Methods: A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The PubMed/Medline, EMBASE, and Cochrane Library databases were searched. The primary outcome was 5-year OS, and the secondary outcome was the 5-year relapse-free survival (RFS). The outcomes were analyzed as odds ratios (ORs) and 95% confidence intervals (CIs). Results: A total of 14 studies were included. Overall, the quality scores were relatively high, and little publication bias was noted. In terms of the 5-year OS, 7 studies were analyzed; there was no significant difference between AS and adjuvant treatment (OR, 0.99; 95% CI, 0.41−2.39; p = 0.97). In terms of 5-year RFS, 12 studies were analyzed. Adjuvant treatment reduced the risk of 5-year recurrence by 85% compared with AS (OR, 0.15; 95% CI, 0.08−0.26; p < 0.001). Conclusions: In terms of the OS in CSI seminoma patients, no intergroup difference was noted, so it is reasonable to offer AS, as recommended by the EAU GORRG until the end of the COVID-19 pandemic. However, since there is a large intergroup difference in the recurrence rate, further research on the long-term (>5 years) outcomes is warranted.
Topics: Male; Humans; Seminoma; COVID-19; Testicular Neoplasms; Urology; Pandemics; Neoplasm Staging; Neoplasm Recurrence, Local; Radiotherapy, Adjuvant
PubMed: 36363471
DOI: 10.3390/medicina58111514 -
Frontiers in Endocrinology 2022Diabetes-induced reproductive complications can lead to subfertility and infertility, raising the need to protect reproductive organs. There are limited medications used...
BACKGROUND
Diabetes-induced reproductive complications can lead to subfertility and infertility, raising the need to protect reproductive organs. There are limited medications used to improve reproductive health in diabetic patients. Melatonin, mainly produced by the pineal gland, may improve diabetes-associated reproductive complications through various mechanisms and may be a preferred candidate to protect the reproductive system. The present review aims to elucidate the underlying mechanisms of melatonin's effect on the reproductive system adversely affected by diabetes mellitus (DM).
METHODS
A comprehensive systematic literature electronic search was done using the PRISMA guidelines. Web of Science, PubMed, Embase, and Scopus were searched for publications up to June 2022. Search terms were selected based on the study purpose and were explored in titles and abstracts. After screening, out of a total of 169 articles, 14 pertinent articles were included based on our inclusion and exclusion criteria.
RESULTS
The results of studies using rats and mice suggest that DM adversely affects reproductive tissues, including testes and epididymis, prostate, corpus cavernosum, and ovary leading to alterations in histological and biochemical parameters compared to the normal groups. Treatment with melatonin improves oxidative stress, blocks apoptosis induced by endoplasmic reticulum stress and caspase activation, reduces pro-inflammation cytokines, and enhances steroidogenesis.
CONCLUSION
Melatonin exerted a protective action on the impaired reproductive system in and models of DM. The topic has to be followed up in human pregnancy cases that will need more time to be collected and approved.
Topics: Male; Female; Humans; Rats; Mice; Animals; Melatonin; Oxidative Stress; Antioxidants; Reproduction; Diabetes Mellitus
PubMed: 36303864
DOI: 10.3389/fendo.2022.1022989 -
European Urology Focus Mar 2023Unlike palpable lumps, a large number of nonpalpable testicular lesions found incidentally at ultrasound in asymptomatic postpuberal males are either benign tumours or... (Review)
Review
CONTEXT
Unlike palpable lumps, a large number of nonpalpable testicular lesions found incidentally at ultrasound in asymptomatic postpuberal males are either benign tumours or non-neoplastic lesions. The prevalence of malignancy, however, is appraised based on small case series. Dedicated studies report a large number of patients, and systematic review articles are lacking.
OBJECTIVE
This systematic review is aimed to assess, from the analysis of the pooled data of the available literature, the incidence of benign tumours, malignant tumours, and non-neoplastic lesions, and to identify predictive characteristics for malignancy.
EVIDENCE ACQUISITION
A systematic review of PubMed, Scopus, Google Scholar, Turning Research Into Practice (TRIP) database, and the Cochrane Library was conducted on January 6, 2022, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Studies were retrieved reporting on adult asymptomatic men, with single, incidentally identified small testicular lesions, either fertile or infertile, with negative tumour markers and without specific risk factors for malignancy. Lesions ≤20 mm were considered small. Seventy-four studies were selected for inclusion in this analysis. Twenty-six additional publications have been retrieved by the bibliography quoted in the selected articles.
EVIDENCE SYNTHESIS
Pooled data of 1348 lesions in 1348 patients were collected. Of these lesions, 408 could be retrieved individually, 44.6% were benign, 27.2% were malignant, and 20.8% were non-neoplastic. Virtually all lesions <3 mm and 86.6% of lesions <5 mm were benign. Lesions >10 mm have a 38.14% probability of being benign. Hyperechoic lesions are likely benign. Fertility status does not affect the risk of malignancy.
CONCLUSIONS
Very small (<3 mm) and small (<5 mm) incidentally detected testicular lesions in asymptomatic postpuberal men with normal tumour markers could be frequently benign. More prospective studies are needed to better support this finding. Management strategies should be developed for these patients to reduce overtreatment.
PATIENT SUMMARY
Small testicular lesions are incidentally founded at ultrasound. It is not easy to distinguish a benign lesion from a malignant one. Results of this study are reporting a higher incidence of benign lesions with a diameter of <5 mm. More studies are needed to better understand the biology and the management strategy for small testicular lesions.
Topics: Male; Humans; Adult; Testicular Neoplasms; Ultrasonography; Prospective Studies; Infertility
PubMed: 36257887
DOI: 10.1016/j.euf.2022.10.001 -
Andrology Mar 2023Men with Klinefelter Syndrome develop some degree of seminiferous tubule degeneration, hyalinization, and fibrosis by adulthood. However, the pathophysiology surrounding... (Review)
Review
BACKGROUND
Men with Klinefelter Syndrome develop some degree of seminiferous tubule degeneration, hyalinization, and fibrosis by adulthood. However, the pathophysiology surrounding testicular fibrosis in Klinefelter Syndrome patients remains incompletely understood.
OBJECTIVES
To perform a systematic review of literature studying the mechanisms of fibrosis initiation or propagation in Klinefelter Syndrome testes.
MATERIALS/METHODS
PubMed was searched systematically for articles specific to Klinefelter Syndrome and the process of fibrosis. Articles that did not contain original data or specifically addressed the target material were excluded. Additional references were extracted when pertinent from the reference lists of included studies.
RESULTS
Primary search yielded 139 articles for abstract review, which was narrowed to 16 for full-text review. Following full-text review, eight contained original data and met topic criteria, with one paper added from reference review for a total of nine papers.
DISCUSSION
The date range for included papers was 1992-2022. The proposed mechanisms of fibrosis mainly were centered around the impact of altered Sertoli cells on germ cells, the hormonal impact on Leydig cells, the inflammation mediated by mast cells, or the fibrous extracellular matrix deposition by peritubular myoid cells. Additionally, discussions of the role of the altered microvasculature and the specific proteins involved in the blood-testis barrier or the seminiferous tubule architecture are reviewed. Recent papers have incorporated advanced sequencing and offer future directions for targeted gene expression analysis. Still, much of the published data consists solely of immunohistological assessment by age range, creating difficulties in extrapolating causality.
CONCLUSION
The specific initiating factors of fibrosis of the seminiferous tubules and the propagation mechanisms unique to Klinefelter Syndrome remain incompletely understood with a relative paucity of data. Nonetheless, academic interest is increasing in this field as it may further elucidate the pathophysiology behind Klinefelter syndrome.
Topics: Male; Humans; Adult; Klinefelter Syndrome; Testis; Seminiferous Tubules; Sertoli Cells; Fibrosis
PubMed: 36252136
DOI: 10.1111/andr.13327 -
Journal of Clinical Medicine Sep 2022Management of incidentally diagnosed small testicular masses (STM) is controversial. Although there is the risk of malignancy, it might be realistic to safely seek... (Review)
Review
Management of incidentally diagnosed small testicular masses (STM) is controversial. Although there is the risk of malignancy, it might be realistic to safely seek preservation of testicles bearing benign masses. This study aims to systematically evaluate the evidence regarding prevalence of STMs, their benign or malignant histology and their management. We conducted a systematic literature search for studies reporting small or incidental testicular masses and their management by radical orchiectomy, testis sparing surgery (TSS) or ultrasound (US) surveillance. We initially screened 2126 abstracts and from these, 57 studies met the inclusion criteria. Testicular masses were detected in 1.74% of patients undergoing US examination. Regarding STMs removed by surgery, 41.12% were benign. Intraoperative frozen section examination (FSE) is a reliable tool to discriminate between benign and malignant testicular masses (average 93.05% accuracy), supporting TSS. Benign lesions were associated with smaller diameter (<1 cm 68.78% benign), were often hypoechoic and exhibited regular margins on US. Conclusions: Small testicular masses are often benign. Clinical and US patterns are not accurate enough for including patients in surveillance protocols and TSS paired with FSE is pivotal for precluding the removal of testicles bearing benign lesions. Future research might unveil new imaging tools or biomarkers to support clinical management.
PubMed: 36233639
DOI: 10.3390/jcm11195770