-
Frontiers in Endocrinology 2023Environmental pollution and infertility are two modern global challenges that agonize personal and public health. The causal relationship between these two deserves... (Meta-Analysis)
Meta-Analysis
Protective effects of melatonin against the toxic effects of environmental pollutants and heavy metals on testicular tissue: A systematic review and meta-analysis of animal studies.
BACKGROUND
Environmental pollution and infertility are two modern global challenges that agonize personal and public health. The causal relationship between these two deserves scientific efforts to intervene. It is believed that melatonin maintains antioxidant properties and may be utilized to protect the testicular tissue from oxidant effects caused by toxic materials.
METHODS
A systematic literature search was conducted in PubMed, Scopus, and Web of Science to identify the animal trial studies that evaluated melatonin therapy's effects on rodents' testicular tissue against oxidative stress caused by heavy metal and non-heavy metal environmental pollutants. Data were pooled, and standardized mean difference and 95% confidence intervals were estimated using the random-effect model. Also, the risk of bias was assessed using the Systematic Review Centre for Laboratory animal Experimentation (SYRCLE) tool. (PROSPERO: CRD42022369872).
RESULTS
Out of 10039 records, 38 studies were eligible for the review, of which 31 were included in the meta-analysis. Most of them showed beneficial effects of melatonin therapy on testicular tissue histopathology. [20 toxic materials were evaluated in this review, including arsenic, lead, hexavalent chromium, cadmium, potassium dichromate, sodium fluoride, cigarette smoke, formaldehyde, carbon tetrachloride (CCl4), 2-Bromopropane, bisphenol A, thioacetamide, bisphenol S, ochratoxin A, nicotine, diazinon, Bis(2-ethylhexyl) phthalate (DEHP), Chlorpyrifos (CPF), nonylphenol, and acetamiprid.] The pooled results showed that melatonin therapy increased sperm count, motility, viability and body and testicular weights, germinal epithelial height, Johnsen's biopsy score, epididymis weight, seminiferous tubular diameter, serum testosterone, and luteinizing hormone levels, testicular tissue Malondialdehyde, glutathione peroxidase, superoxide dismutase, and glutathione levels. On the other hand, abnormal sperm morphology, apoptotic index, and testicular tissue nitric oxide were lower in the melatonin therapy arms. The included studies presented a high risk of bias in most SYRCLE domains.
CONCLUSION
In conclusion, our study demonstrated amelioration of testicular histopathological characteristics, reproductive hormonal panel, and tissue markers of oxidative stress. Melatonin deserves scientific attention as a potential therapeutic agent for male infertility.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO, identifier CRD42022369872.
Topics: Animals; Male; Melatonin; Environmental Pollutants; Semen; Testis; Antioxidants
PubMed: 36793277
DOI: 10.3389/fendo.2023.1119553 -
Asian Journal of Surgery Dec 2021Testis-sparing surgery (TSS) has been increasingly used for treating a variety of testicular tumors (TTs) in children. However, the indications and feasibility... (Meta-Analysis)
Meta-Analysis Review
Testis-sparing surgery (TSS) has been increasingly used for treating a variety of testicular tumors (TTs) in children. However, the indications and feasibility associated with TSS remain uncertain. This study aimed to present the clinical outcomes of TSS in children with TTs. The PubMed, Cochrane Library, and Embase databases were reviewed for relevant articles on the clinical outcomes of TSS in children. Recurrence rate, benign rate, rate of TSS and its 95% confidence interval (CI) were calculated. A total of nine relevant studies with 320 patients were included in this study. The recurrence rate was 5.8% (95% CI: 2.3%-14.1%), benign rate was 70.9% (95% CI: 56.3%-82.1%), the rate of TSS (RTSS) was 36.2% (95% CI: 26.1%-47.8%), RTSS in benign tumor was 48.4% (95% CI: 34.3%-62.9%) and rate of elevated AFP was 29.3% (95% CI: 19.7%-41.3%) in children with TTs. Regarding the distribution of TTs, 159 (49.6%) were teratomas, 74 (23.1%) were yolk sac tumors, 36 (11.3%) were epidermoid cysts, 3 (0.9%) were rhabdomyosarcomas, 7 (2.2%) were leydig cell tumor, 6 (1.8%) were sex-cord stromal tumor, 8(2.5%) were mixed malignant germ cell tumors, 3(0.9%) were hemangioma, and 4(1.3%) were adrenal rest tumors. The findings of this meta-analysis suggested that most of the TTs in children were benign, and the most common histologic subtype was teratoma. TSS should be provided to children with benign lesions. This study confirmed that very low rates of tumor recurrence were observed in children with TTs.
Topics: Epidermal Cyst; Humans; Male; Testicular Neoplasms
PubMed: 33893031
DOI: 10.1016/j.asjsur.2021.03.016 -
Andrology Mar 2022Some evidence suggests that diabetes mellitus type 1 (DM1) could affect male fertility, gonadal axis, semen parameters, and spermatogenesis because of effects of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Some evidence suggests that diabetes mellitus type 1 (DM1) could affect male fertility, gonadal axis, semen parameters, and spermatogenesis because of effects of hyperglycemia and insulin deficiency. Anyhow, the exact impact of DM1 on male fertility is unclear.
OBJECTIVES
To review the studies evaluating paternity rate, male gonadal axis, and semen parameters in men with DM1.
MATERIALS AND METHODS
A review of relevant literature from January 1980 to December 2020 was performed. Only studies published in English reporting data on fatherhood (rate of children by natural fertility), hormonal and seminal parameters were included. Out of 14 retrieved articles, the eight studies evaluating semen parameters were meta-analyzed.
RESULTS
The rate of children (four studies) was lower than controls among men affected by DM1, especially in men with a longer duration of disease. The data of gonadal hormonal profile in DM1 men (six studies) are very heterogeneous and a neutral effect of DM1 or a condition of subclinical hypogonadism could not be concluded. Meta-analysis showed that men with DM1 (n = 380), compared with controls (n = 434), have significantly lower normal sperm morphology [-0.36% (-0.66; -0.06), p < 0.05, six studies] and sperm progressive motility [33.62% (-39.13; -28.11), p < 0.001, two studies] and a trend toward a lower seminal volume [-0.51 (-1.03; 0.02), p = 0.06, eight studies], without difference in total sperm count and concentration. Data on scrotal ultrasound and sperm DNA fragmentation are too few. No study evaluated other factors of male infertility, such as transrectal ultrasound, semen infections, sperm auto-antibodies, and retrograde ejaculation.
DISCUSSION
DM1 might impair male fertility and testis functions (endocrine, spermatogenesis), but definition of its actual impact needs further studies.
CONCLUSION
Men with DM1 should be evaluated with a complete hormonal, seminal, and ultrasound workup to better define their fertility potential and need for follow up of testis functions.
Topics: Child; Diabetes Mellitus; Fertility; Humans; Infertility, Male; Male; Semen; Semen Analysis; Sperm Count; Sperm Motility; Spermatozoa
PubMed: 34904793
DOI: 10.1111/andr.13140 -
Life Sciences Apr 2022Plastic particles (PP) pollution is a global environmental concern. Although the reproductive toxicity of PP is primarily understood for invertebrates, the evidence for... (Review)
Review
AIMS
Plastic particles (PP) pollution is a global environmental concern. Although the reproductive toxicity of PP is primarily understood for invertebrates, the evidence for mammals is still fragmented. We used a systematic review framework to investigate the reproductive impact of microplastics and nanoplastics (MNP) on mammals.
MATERIALS AND METHODS
Research records were screened from Embase, Medline, Scopus and Web of Science. Twelve original papers were identified and reviewed. Immunological, oxidative and morphofunctional outcomes, and the risk of bias in all studies reviewed were analyzed.
KEY FINDINGS
These studies indicated that PP can accumulate in the gonads, triggering seminiferous degeneration, Sertoli cells death, blood-testis barrier disruption, sperm degeneration, malformation, reduced number and mobility, ovarian cysts, reduced follicular growth and granulosa cells death. Gonadal damage was associated with upregulation of prooxidant mediators (oxygen reactive species, lipid and DNA oxidation), cell death, proinflammatory molecular pathways and cytokines, as well as inhibition of enzymatic and non-enzymatic antioxidant defense mechanisms. Spermatogenesis, folliculogenesis, testosterone, progesterone and estrogen levels were also impaired in PP-treated animals, which were potentially associated with down-regulation of molecules involved in germ cells microstructural organization (occludin, N-cadherin, β-catenin and connexin 43) and steroidogenesis, such as hydroxysteroid dehydrogenases, steroidogenic acute regulatory proteins, follicle stimulating and luteinizing hormones. Selection, performance and detection bias were the main limitations identified.
SIGNIFICANCE
Current evidence indicates that PP can induce dose-dependent microstructural and functional gonadal damage, which is orchestrated by pro-oxidant and pro-inflammatory mechanisms that disrupt genes, molecular effectors, and hormones that control spermatogenesis and folliculogenesis.
Topics: Animals; Estrogens; Female; Genitalia; Germ Cells; Granulosa Cells; Inflammation; Intestinal Mucosa; Luteinizing Hormone; Male; Mammals; Microplastics; Ovarian Follicle; Ovary; Oxidative Stress; Plastics; Progesterone; Reproduction; Sertoli Cells; Spermatogenesis; Testis; Testosterone
PubMed: 35176278
DOI: 10.1016/j.lfs.2022.120404 -
International Journal of Cancer Nov 2019Firefighters are exposed to both known and suspected carcinogens. This study aims to systematically review the literature on the association of firefighting occupation... (Meta-Analysis)
Meta-Analysis
Firefighters are exposed to both known and suspected carcinogens. This study aims to systematically review the literature on the association of firefighting occupation and cancer incidence and mortality, overall and for specific cancer sites. A systematic review using PubMed, Embase, and Web of Science was performed up to January 1, 2018. We extracted risk estimates of cancers and calculated summary incidence risk estimates (SIRE), summary mortality risk estimates (SMRE), and their 95% confidence intervals (CI). Publication bias and risk of bias in individual studies were assessed using Begg's and Egger's tests and the Newcastle-Ottawa scale (NOS), respectively. We included 50 papers in the review and 48 in the meta-analysis. We found significantly elevated SIREs for cancer of the colon (1.14; CI 1.06 to 1.21), rectum (1.09; CI 1.00 to 1.20), prostate (1.15; CI 1.05 to 1.27), testis (1.34; CI 1.08 to 1.68), bladder (1.12; CI 1.04 to 1.21), thyroid (1.22; CI 1.01 to 1.48), pleura (1.60; CI 1.09 to 2.34), and for malignant melanoma (1.21; CI 1.02 to 1.45). We found significant SMREs of 1.36 (1.18 to 1.57) and 1.42 (1.05 to 1.90) for rectal cancer and Non-Hodgkin's lymphoma, respectively. Considering the significantly elevated risk of some cancers in this occupational group, we suggest improving preventive measures and securing adequate and relevant medical attention for this group. Further studies with more accurate and in-depth exposure assessments are indicated.
Topics: Carcinogens; Firefighters; Humans; Incidence; Neoplasms; Occupational Exposure; Risk Assessment; Survival Analysis
PubMed: 30737784
DOI: 10.1002/ijc.32199 -
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 -
Journal of Pediatric Urology Apr 2020Genitourinary injuries in athletes engaging in high-impact sports such as football and rugby may have catastrophic consequences, especially in individuals with... (Review)
Review
BACKGROUND
Genitourinary injuries in athletes engaging in high-impact sports such as football and rugby may have catastrophic consequences, especially in individuals with pre-existing urologic concerns, such as a solitary kidney.
OBJECTIVE
To summarize the current literature on football-related or rugby-related genitourinary organ injuries in both adult and pediatric populations in an effort to risk stratify the likelihood of these injuries.
METHODS
An independent systematic literature search for records reporting football-related or rugby-related injuries was conducted by a certified librarian and reviewer in March 2019. The search electronic databases included Medline, EMBASE, Scopus, and Web of Science. All studies reporting football-related or rugby-related genitourinary injuries were included.
RESULTS
Twenty-two records (11 research studies, 11 case reports) were identified. In the pediatric population, the reported football-related kidney injuries were 0.1-0.7% of all football-related injuries, 0.07-0.5% of all sports-related injuries, and 1.5-37.5% of all sports-related genitourinary injuries, with incidence ranging from 0.00000084 to 0.0000092 injuries per exposure (five studies). Pediatric football-related testicular injuries were reported to be 0.11% of all football injuries, 0-0.07% of all sports-related injuries, and 0-37.5% of all sports-related genitourinary injuries; injury per exposure was 0.0000092 (four studies). In adults, there was no proportion of genitourinary injuries that could be determined, and football-related kidney injury incidence was 0.000012 injuries per exposure (one study). No adult literature investigated testicular injuries. Eleven case reports were additionally identified. Review of the case reports suggests that patients with previously existing urologic abnormalities such as ureteropelvic junction obstruction may predispose an individual to kidney injuries.
CONCLUSION
There is little to suggest that those engaged in football or rugby have a significant risk of genitourinary injury; therefore, future guidelines should reflect this.
Topics: Adult; Athletes; Athletic Injuries; Child; Football; Humans; Incidence; Risk Factors
PubMed: 32029358
DOI: 10.1016/j.jpurol.2019.12.019 -
European Journal of Endocrinology Jan 2024Hypogonadotropic hypogonadism is characterized by inadequate secretion of pituitary gonadotropins, leading to absent, partial, or arrested puberty. In males, classical... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Hypogonadotropic hypogonadism is characterized by inadequate secretion of pituitary gonadotropins, leading to absent, partial, or arrested puberty. In males, classical treatment with testosterone promotes virilization but not testicular growth or spermatogenesis. To quantify treatment practices and efficacy, we systematically reviewed all studies investigating gonadotropins for the achievement of pubertal outcomes in males with hypogonadotropic hypogonadism.
DESIGN
Systematic review and meta-analysis.
METHODS
A systematic review of Medline, Embase, Global Health, and PsycINFO databases in December 2022. Risk of Bias 2.0/Risk Of Bias In Non-randomized Studies of Interventions/National Heart, Lung, and Blood Institute tools for quality appraisal. Protocol registered on PROSPERO (CRD42022381713).
RESULTS
After screening 3925 abstracts, 103 studies were identified including 5328 patients from 21 countries. The average age of participants was <25 years in 45.6% (n = 47) of studies. Studies utilized human chorionic gonadotropin (hCG) (n = 93, 90.3% of studies), human menopausal gonadotropin (n = 42, 40.8%), follicle-stimulating hormone (FSH) (n = 37, 35.9%), and gonadotropin-releasing hormone (28.2% n = 29). The median reported duration of treatment/follow-up was 18 months (interquartile range 10.5-24 months). Gonadotropins induced significant increases in testicular volume, penile size, and testosterone in over 98% of analyses. Spermatogenesis rates were higher with hCG + FSH (86%, 95% confidence interval [CI] 82%-91%) as compared with hCG alone (40%, 95% CI 25%-56%). However, study heterogeneity and treatment variability were high.
CONCLUSIONS
This systematic review provides convincing evidence of the efficacy of gonadotropins for pubertal induction. However, there remains substantial heterogeneity in treatment choice, dose, duration, and outcomes assessed. Formal guidelines and randomized studies are needed.
Topics: Humans; Male; Chorionic Gonadotropin; Follicle Stimulating Hormone; Gonadotropin-Releasing Hormone; Gonadotropins; Hypogonadism; Klinefelter Syndrome; Spermatogenesis; Testis; Testosterone; Young Adult
PubMed: 38128110
DOI: 10.1093/ejendo/lvad166 -
Children (Basel, Switzerland) Jul 2022The external genitalia are notoriously implicated in every fifth male with Henoch−Schönlein syndrome. Nonetheless, the underlying conditions are poorly categorized.... (Review)
Review
The external genitalia are notoriously implicated in every fifth male with Henoch−Schönlein syndrome. Nonetheless, the underlying conditions are poorly categorized. To characterize the involvement of the external male genitalia in this vasculitis, we performed a systematic review of the literature. For the final analysis, we selected 85 reports published between 1972 and 2022, which reported on 114 Henoch−Schönlein cases (≤ 18 years, N = 104) with a penile (N = 18), a scrotal (N = 77), or both a penile and a scrotal (N = 19) involvement. The genital involvement mostly appeared concurrently with or after the cutaneous features of Henoch−Schönlein syndrome, while it preceded the presentation of Henoch−Schönlein syndrome in 10 cases. Patients with penile involvement (N = 37) presented with swelling (N = 26), erythema (N = 23), and purpuric rash (N = 15). Most patients were otherwise asymptomatic except for transient micturition disorders (N = 2) or priapism (N = 2). Patients with scrotal involvement (N = 96) presented with pain (N = 85), swelling (N = 79), erythema (N = 42), or scrotal purpura (N = 22). The following scrotal structures were often involved: scrotal skin (N = 83), epididymis (N = 49), and testes (N = 39). An ischemic testicular damage was noted in nine patients (four with torsion and five without). The scrotal skin involvement was mostly bilateral, while that of the epididymis and testis were mostly (p < 0.0001) unilateral (with a significant predilection for the left side). In conclusion, this analysis allows for better categorization of the involvement of external male genitalia in Henoch−Schönlein vasculitis. Scrotal involvement can result from skin inflammation, epididymitis, orchitis, or testicular ischemia.
PubMed: 36010045
DOI: 10.3390/children9081154 -
Minerva Urology and Nephrology Aug 2021The prevalence of testicular tumor is constantly increasing, with an estimated incidence rate of about 3-10 new cases per 100,000 males/per year. Radical orchiectomy or...
INTRODUCTION
The prevalence of testicular tumor is constantly increasing, with an estimated incidence rate of about 3-10 new cases per 100,000 males/per year. Radical orchiectomy or testis sparing surgery (TSS) are recognized therapeutic approaches in these cases. However, the risk for hypogonadism and infertility is higher with the former compared with the latter. The aim of this systematic review is to evaluate the oncological outcome and testicular function (endocrine and reproductive aspects) in patients who had undergone TSS for small testicular lesions.
EVIDENCE ACQUISITION
To accomplish this, 684 articles were retrieved and screened; 24 retrospective and two prospective studies were selected and finally included in this systematic review.
EVIDENCE SYNTHESIS
Overall the TSS attempts were 1096 but TSS was definitively performed in 603 cases (55%). Frozen section examination was performed in 996 TSS attempts (22 out of the 26 studies selected) and showed a benign histology in 37-100% of cases, a malignant histology in 0-63%, and an inconclusive result in 0-16%, respectively. Five studies reported that a total of 22 patients were able to father after conservative surgery. None of these studies reported cases of hypotestosteronemia after surgery and a low prevalence (1.66%) of complications was associated with this type of surgery.
CONCLUSIONS
In conclusion, TSS showed to be safe and practicable if used according to the specific guidelines. It can be safely performed to treat recurrence eventually associated to local adjuvant radiotherapy when an intra-tubular neoplasia is present. Urologists can therefore consider TSS as an important means against testicular tumor in selected and well-informed patients.
Topics: Frozen Sections; Humans; Male; Orchiectomy; Prospective Studies; Retrospective Studies; Testicular Neoplasms; Testis
PubMed: 33949185
DOI: 10.23736/S2724-6051.21.04330-5