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Andrologia Oct 2020We performed this systematic review to evaluate the possibility of an impact of SARS-CoV-2 infection on male fertility. SARS-CoV-2 enters the cells with the help of...
We performed this systematic review to evaluate the possibility of an impact of SARS-CoV-2 infection on male fertility. SARS-CoV-2 enters the cells with the help of ACE2; therefore, testicular expression of ACE2 was analysed from transcriptome sequencing studies and our unpublished data. Literature suggested that SARS-CoV-1 (2002-2004 SARS) had a significant adverse impact on testicular architecture, suggesting a high possibility of the impact of SARS-CoV-2 as well. Out of two studies on semen samples from COVID-19 affected patients, one reported the presence of SARS-CoV-2 in the semen samples while the other denied it, raising conflict about its presence in the semen samples and the possibility of sexual transmission. Our transcriptome sequencing studies on rat testicular germ cells showed ACE expression in rat testicular germ cells. We also found ACE2 expression in transcriptome sequencing data for human spermatozoa, corroborating its presence in the testicular germ cells. Transcriptome sequencing data from literature search revealed ACE2 expression in the germ, Sertoli and Leydig cells. The presence of ACE2 on almost all testicular cells and the report of a significant impact of previous SARS coronavirus on testes suggest that SARS-CoV-2 is highly likely to affect testicular tissue, semen parameters and male fertility.
Topics: Angiotensin-Converting Enzyme 2; Animals; Betacoronavirus; COVID-19; Coronavirus Infections; Gene Expression Profiling; Humans; Infertility, Male; Male; Models, Animal; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Rats; SARS-CoV-2; Semen; Spermatozoa; Spike Glycoprotein, Coronavirus; Testis
PubMed: 32578263
DOI: 10.1111/and.13712 -
The Oncologist Jul 2020Sertoli cell tumors (SCTs) of the testes are rare, and the literature provides only weak evidence concerning their clinical course and management. The objective of this... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Sertoli cell tumors (SCTs) of the testes are rare, and the literature provides only weak evidence concerning their clinical course and management. The objective of this study was to summarize evidence on SCTs' clinical presentation, clinicopathological risk factors for malignancy, treatment options, and oncological outcomes.
MATERIALS AND METHODS
Data sources included Medline, Embase, Scopus, the Cochrane Database of Systematic Reviews, and Web of Science. Published case reports, case series, and cohorts were included. Data on clinicopathological variables, treatment of local or metastatic disease, site of metastasis, or survival were extracted from each study considered in this paper, and associations between clinicopathological variables and metastatic disease were analyzed. Whenever feasible, data on individual patients were collected.
RESULTS
Of the 435 patients included, only one (<1%) showed local recurrence after testis-sparing surgery (TSS). Three patients underwent adjuvant retroperitoneal lymphadenectomy. Fifty patients presented with metastases, located in the retroperitoneal lymph nodes (76%), lungs (36%), and bones (16%); median time to recurrence was 12 months. Risk factors for metastatic disease included age, tumor size, necrosis, tumor extension to the spermatic cord, angiolymphatic invasion, and mitotic index. Patients with metastases had a median life expectancy of 20 months. In six patients, metastasectomy resulted in complete remission.
CONCLUSION
Our findings suggest that few local recurrences result after TSS, and no adjuvant therapy can be regarded as a standard of care. Several risk factors are predictive of metastatic disease. Surgery leads to remission in metastatic disease, whereas systemic treatment alone does not result in long-term remission.
IMPLICATIONS FOR PRACTICE
Testicular Sertoli cell tumors usually present without metastatic disease and show low local recurrence rates after testis-sparing surgery; no adjuvant therapy option can be regarded as a standard of care. Patients with risk factors should undergo staging investigations. Those with metastatic disease have poor prognoses, and metastasectomy may be offered in selected cases.
Topics: Humans; Lymph Node Excision; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Sertoli Cell Tumor; Systematic Reviews as Topic; Testicular Neoplasms
PubMed: 32043680
DOI: 10.1634/theoncologist.2019-0692 -
Human Reproduction Update Jul 2019Overall, the incidence of male reproductive disorders has increased in recent decades. Testicular development during fetal life is crucial for subsequent male...
BACKGROUND
Overall, the incidence of male reproductive disorders has increased in recent decades. Testicular development during fetal life is crucial for subsequent male reproductive function. Non-genomic factors such as environmental chemicals, pharmaceuticals and lifestyle have been proposed to impact on human fetal testicular development resulting in subsequent effects on male reproductive health. Whilst experimental studies using animal models have provided support for this hypothesis, more recently a number of experimental studies using human tissues and cells have begun to translate these findings to determine direct human relevance.
OBJECTIVE AND RATIONALE
The objective of this systematic review was to provide a comprehensive description of the evidence for effects of prenatal exposure(s) on human fetal testis development and function. We present the effects of environmental, pharmaceutical and lifestyle factors in experimental systems involving exposure of human fetal testis tissues and cells. Comparison is made with existing epidemiological data primarily derived from a recent meta-analysis.
SEARCH METHODS
For identification of experimental studies, PubMed and EMBASE were searched for articles published in English between 01/01/1966 and 13/07/2018 using search terms including 'endocrine disruptor', 'human', 'fetal', 'testis', 'germ cells', 'testosterone' and related search terms. Abstracts were screened for selection of full-text articles for further interrogation. Epidemiological studies involving exposure to the same agents were extracted from a recent systematic review and meta-analysis. Additional studies were identified through screening of bibliographies of full-texts of articles identified through the initial searches.
OUTCOMES
A total of 25 experimental studies and 44 epidemiological studies were included. Consistent effects of analgesic and phthalate exposure on human fetal germ cell development are demonstrated in experimental models, correlating with evidence from epidemiological studies and animal models. Furthermore, analgesic-induced reduction in fetal testosterone production, which predisposes to the development of male reproductive disorders, has been reported in studies involving human tissues, which also supports data from animal and epidemiological studies. However, whilst reduced testosterone production has been demonstrated in animal studies following exposure(s) to a variety of environmental chemicals including phthalates and bisphenol A, these effects are not reproduced in experimental approaches using human fetal testis tissues.
WIDER IMPLICATIONS
Direct experimental evidence for effects of prenatal exposure(s) on human fetal testis development and function exists. However, for many exposures the data is limited. The increasing use of human-relevant models systems in which to determine the effects of environmental exposure(s) (including mixed exposures) on development and function of human tissues should form an important part of the process for assessment of such exposures by regulatory bodies to take account of animal-human differences in susceptibility.
Topics: Animals; Drug-Related Side Effects and Adverse Reactions; Endocrine Disruptors; Environmental Exposure; Female; Fetal Development; Humans; Male; Pharmaceutical Preparations; Pregnancy; Prenatal Care; Prenatal Exposure Delayed Effects; Testis; Testosterone
PubMed: 30869130
DOI: 10.1093/humupd/dmz004 -
Journal of Animal Science Dec 2018Reduced bull fertility imposes economic losses in bovine herds. Specifically, testicular and spermatic traits are important indicators of reproductive efficiency....
Reduced bull fertility imposes economic losses in bovine herds. Specifically, testicular and spermatic traits are important indicators of reproductive efficiency. Several genome-wide association studies (GWAS) have identified genomic regions associated with these fertility traits. The aims of this study were as follows: 1) to perform a systematic review of GWAS results for spermatic and testicular traits in cattle and 2) to identify key functional candidate genes for these traits. The identification of functional candidate genes was performed using a systems biology approach, where genes shared between traits and studies were evaluated by a guilt by association gene prioritization (GUILDify and ToppGene software) in order to identify the best functional candidates. These candidate genes were integrated and analyzed in order to identify overlapping patterns among traits and breeds. Results showed that GWAS for testicular-related traits have been developed for beef breeds only, whereas the majority of GWAS for spermatic-related traits were conducted using dairy breeds. When comparing traits measured within the same study, the highest number of genes shared between different traits was observed, indicating a high impact of the population genetic structure and environmental effects. Several chromosomal regions were enriched for functional candidate genes associated with fertility traits. Moreover, multiple functional candidate genes were enriched for markers in a species-specific basis, taurine (Bos taurus) or indicine (Bos indicus). For the different candidate regions identified in the GWAS in the literature, functional candidate genes were detected as follows: B. Taurus chromosome X (BTX) (TEX11, IRAK, CDK16, ATP7A, ATRX, HDAC6, FMR1, L1CAM, MECP2, etc.), BTA17 (TRPV4 and DYNLL1), and BTA14 (MOS, FABP5, ZFPM2). These genes are responsible for regulating important metabolic pathways or biological processes associated with fertility, such as progression of spermatogenesis, control of ciliary activity, development of Sertoli cells, DNA integrity in spermatozoa, and homeostasis of testicular cells. This study represents the first systematic review on male fertility traits in cattle using a system biology approach to identify key candidate genes for these traits.
Topics: Animals; Cattle; Genome-Wide Association Study; Male; Polymorphism, Single Nucleotide; Spermatozoa; Testis
PubMed: 30304443
DOI: 10.1093/jas/sky382 -
Journal of Pediatric Hematology/oncology Jul 2017It has been reported that germline DICER1 mutations correlate with a distinctive human disease syndrome. Many published studies within this field have been conducted... (Meta-Analysis)
Meta-Analysis Review
It has been reported that germline DICER1 mutations correlate with a distinctive human disease syndrome. Many published studies within this field have been conducted based on rare cases. We systematically searched bibliographic databases, including PubMed, Embase, and COSMIC for articles which are related to diseases covered by DICER1 syndrome. The weighted summary of mutation frequencies among patients with pleuropulmonary blastoma (PPB), cystic nephroma (CN), and Sertoli-Leydig cell tumor (SLCT) were calculated. Forty-nine eligible articles were included. In total, 72 cases with multimorbidity of DICER1 syndrome were identified. More females (n=46, 64%) presented with multimorbidity than males (n=18, 25%) and the remaining 8 patients' sex were unknown. Nineteen of 72 patients with multimorbidity suffered from another disease that was not yet included in DICER1 syndrome, which would provide potential phenotypes of DICER1 syndrome. The germline DICER1 mutation frequencies in PPB, CN, and SLCT were 66.9%, 73.2%, and 57.1%, respectively. The somatic DICER1 mutation frequencies of PPB, CN, and SLCT were 92.4%, 87.9%, and 43.3%, respectively. Majority of patients with multimorbidity of DICER1 syndrome were mutation positive individuals so that multimorbidity may suggest the possible germline mutation of these patients and their relatives.
Topics: DEAD-box RNA Helicases; Female; Germ-Line Mutation; Humans; Male; Mutation Rate; Nephroma, Mesoblastic; Pulmonary Blastoma; Ribonuclease III; Sertoli-Leydig Cell Tumor
PubMed: 27906793
DOI: 10.1097/MPH.0000000000000715 -
Environmental Science and Pollution... Feb 2017Diverse industries like detergents, resins and polymers, hair dyes, intravaginal spermicides, and pesticides produce endocrine disruptor (ED)-containing wastewaters that... (Review)
Review
Diverse industries like detergents, resins and polymers, hair dyes, intravaginal spermicides, and pesticides produce endocrine disruptor (ED)-containing wastewaters that have hazardous effects on the environment and public health. Nonylphenol (NP) is a chemical substance that consists of a phenolic group and an attached lipophilic linear nonyl chain. NP has weak estrogenic activity and affects estrogen receptor (ER), as well as induces male infertility via a negative impact on spermatogenesis and sperm quality. The aim of this study was to comprehensively review all available literature about the side effects of NP on the male genital system. We systematically searched Scopus and PubMed using MeSH terms that include "Organic Chemicals," "Infertility," "Infertility, Male," "Nonylphenol", ("Infertility, Male"[Mesh]) OR "Nonylphenol" [Supplementary Concept]) OR "Prostate"[Mesh]) OR "Spermatozoa"[Mesh]) OR "Sertoli Cells"[Mesh]) OR "Leydig Cells"[Mesh] OR "Male accessory gland" OR "Epididym" OR "Reproductive toxicity"), and all other possible combinations from January 1, 1970, to September 15, 2016, with language limit. The initial search identified 117,742 potentially eligible studies, of which 33 met the established inclusion criteria and were included in the analysis. Thirty-three selected studies include animal model (n = 18), cell line (n = 15), human model (n = 1), morphology (n = 13), sperm quality (n = 17), and toxicity (n = 14). This review highlighted the evidence for the ED effect of NP that acts through interference with ER, discussing male reproductive tract perturbations. We critically discuss the available evidence on the effect of NP on sperm quality (such as motility, viability, sperm count, and sperm concentration), dramatic morphological changes (such as change of weights of testes and epididymis), and biochemical changes related to oxidative stress in testes. Finally, it is important to take caution with the continued use of NP that disrupts male reproductive health.
Topics: Animals; Fertility; Humans; Infertility, Male; Male; Phenols; Sperm Count; Spermatogenesis; Spermatozoa
PubMed: 27826822
DOI: 10.1007/s11356-016-7960-y -
European Journal of Obstetrics,... Apr 2014Sex-cord stromal tumors (SCSTs) are rare ovarian cancers and their behavior during pregnancy is not well understood. To evaluate the maternal and fetal outcomes of... (Review)
Review
Sex-cord stromal tumors (SCSTs) are rare ovarian cancers and their behavior during pregnancy is not well understood. To evaluate the maternal and fetal outcomes of pregnancy complicated by ovarian SCST, a systematic literature search was conducted in PubMed/MEDLINE using entry key words "pregnancy" and each type of ovarian SCST ("sex cord stromal tumor," "granulosa cell tumor," "thecoma," "Sertoli-Leydig cell tumor," or "gynandroblastoma") between 1955 and 2012 that identified 46 cases eligible for the analysis. Clinical characteristics, pregnancy outcome, tumor characteristics, and survival outcomes were evaluated. Serious adverse events were defined as complications related to the SCST that resulted in severe morbidity or mortality for mother, fetus, or both. The most common histology was granulosa cell tumor (22.0%), followed by thecoma (18.6%) and Sertoli-Leydig cell tumor (8.5%). Abdomino-pelvic pain (45.7%), palpable mass (30.4%), and virilization (26.1%) were the three most common symptoms. The majority were stage I (76.1%), tumor size <15cm (64.9%), and underwent unilateral adnexectomy (80.4%). Fetal conservation surgery was seen in 54.3%. Most cases had live births (78.3%) at full term (60.9%). Among cases proceeded expectant delay of delivery (45.7%), most cases resulted in live birth (95.2%) with median expectant interval of 20.7 weeks. Maternal and/or fetal serious adverse events (SAEs) were observed in 41.3% with maternal shock/hemoperitoneum being the most common complication (13.0%). Logistic regression test identified younger age (<30 versus ≥30, 73.3% versus 26.7%, odds ratio [OR] 11.7, 95%CI 1.35-101, p=0.026), large tumor (size ≥15cm versus <15cm, 64.9% versus 35.1%, OR 10.0, 95%CI 1.29-26.2, p=0.004), and advanced-stage (stages II-IV versus I, 76.1% versus 23.9%, OR 5.82, 95%CI 2.05-48.9, p=0.022) as risk factors of increased SAE. Overall survival of patients diagnosed with ovarian SCST during pregnancy was comparable to ovarian SCST not related to pregnancy (5-year rate, stages I and II-IV, 100% and 70.0%, respectively). In conclusion, although the majority of cases resulted in live birth, ovarian SCST-complicated pregnancy falls into the category of high-risk pregnancy. Risk factors for SAE identified in our study will help to guide strategic management of pregnancy complicated by ovarian SCST.
Topics: Female; Humans; Ovarian Neoplasms; Pregnancy; Pregnancy Complications, Neoplastic; Pregnancy Outcome; Sex Cord-Gonadal Stromal Tumors
PubMed: 24439718
DOI: 10.1016/j.ejogrb.2013.12.025 -
Andrology Jan 2014Retrieval of spermatozoa is unfortunately still only successful in a subset of patients suffering from non-obstructive azoospermia (NOA) by conventional testicular sperm... (Review)
Review
Retrieval of spermatozoa is unfortunately still only successful in a subset of patients suffering from non-obstructive azoospermia (NOA) by conventional testicular sperm extraction (TESE). Microdissection TESE may have some theoretical benefits over conventional TESE, but uncertainty exists about its superiority. The objective of this systematic review was therefore to compare the efficacy and safety of microTESE with conventional TESE in men with NOA. The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. Literature was searched for studies comparing outcome of conventional TESE with microdissection TESE. Primary outcome was sperm retrieval rate (SRR). Secondary outcomes were clinical predictors of sperm retrieval as well as complication rate. Of 62 articles, a total of seven studies were included in the final analysis. Overall SRR was significantly higher in the microTESE group in comparison with conventional TESE in five of these studies. Overall sperm retrieval ranged from 16.7 to 45% in the conventional TESE vs. 42.9 to 63% in the microTESE group. A sub-analysis of the SRR according to testicular histology was available in four of the selected articles. MicroTESE in men with Sertoli cell only syndrome and hypospermatogenesis carried a small but significant more favourable outcome according to, respectively, two and one of the studies. Correlation of serum follicle stimulating hormone and testicular volume with positive outcome was variable. Fewer complications were observed on ultrasound examination after microTESE procedure. Clinical randomized studies comparing microTESE with conventional TESE in NOA are still lacking to date. Pseudo-randomized prospective data, however, show more favourable sperm retrieval in NOA for microTESE, especially in histological patterns of patchy spermatogenesis such as Sertoli cell only syndrome. However, in patients with uniform histological patterns such as maturation arrest outcome of microTESE seems less favourable.
Topics: Azoospermia; Follicle Stimulating Hormone; Humans; Male; Microdissection; Oligospermia; Sertoli Cell-Only Syndrome; Sperm Retrieval; Spermatozoa; Testis; Treatment Outcome; Ultrasonography
PubMed: 24193894
DOI: 10.1111/j.2047-2927.2013.00148.x -
Human Reproduction Update 2010A non-invasive test, which could predict the presence of sperm during a testicular sperm extraction (TESE) procedure in men with non-obstructive azoospermia (NOA), would... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
A non-invasive test, which could predict the presence of sperm during a testicular sperm extraction (TESE) procedure in men with non-obstructive azoospermia (NOA), would be of profound clinical importance. Inhibin B (Inh-B) and anti-Müllerian hormone (AMH) have been proposed as direct markers of Sertoli cell function and indirect markers of spermatogenesis.
METHODS
A search was conducted in the electronic databases MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials from inception through June 2009. Thirty-six different studies reported data on the predictive value of one or more index markers (serum Inh-B: 32 studies, seminal Inh-B: 5 studies, serum AMH: 2 studies, seminal AMH: 4 studies) and were included in the systematic review. Nine studies, which had serum Inh-B as index marker, met the predefined criteria and were included in the meta-analysis.
RESULTS
Serum Inh-B demonstrated a sensitivity of 0.65 (95% confidence interval [CI]: 0.56-0.74) and a specificity of 0.83 (CI: 0.64-0.93) for the prediction of the presence of sperm in TESE. When the pre-test probability of 41% was incorporated in a Fagan's nomogram, resulted in a positive post-test probability of 73% and a negative post-test probability of 23% for the presence of sperm in TESE.
CONCLUSIONS
Serum Inh-B cannot serve as a stand-alone marker of persistent spermatogenesis in men with NOA. Although limited, evidence on serum AMH and serum/seminal AMH do not support their diagnostic value in men with NOA.
Topics: Anti-Mullerian Hormone; Azoospermia; Humans; Inhibins; Male; Predictive Value of Tests; Spermatogenesis
PubMed: 20601364
DOI: 10.1093/humupd/dmq024 -
Human Reproduction Update 2007Our objective was to establish which is the best sperm retrieval technique in non-obstructive azoospermia based on the available evidence. To date, no randomized... (Review)
Review
Our objective was to establish which is the best sperm retrieval technique in non-obstructive azoospermia based on the available evidence. To date, no randomized controlled trial has compared the efficiency of these strategies and thus current recommendations are based on cumulative evidence provided by descriptive, observational and controlled studies. Three outcome measures were assessed for the sperm retrieval techniques: sperm retrieval rate (SRR), complications and live birth rate. Twenty-four descriptive studies reporting on the results of testicular sperm extraction (TESE) were encountered. Seven controlled studies that compared microdissection (MD) TESE with conventional TESE and seven controlled studies comparing fine needle testicular aspiration (FNA) with TESE were identified. The mean SRR for TESE was 49.5% (95% CI 49.0-49.9). TESE with multiple biopsies results in a higher SRR than FNA especially in cases of Sertoli-cell-only (SCO) syndrome and maturation arrest. Current evidence suggests that MD performs better than conventional TESE only in cases of SCO where tubules containing active focus of spermatogenesis can be identified. MD appears to be the safest technique regarding post-operative complications followed by FNA. Only three studies could be identified concerning the influence of the sperm retrieval technique on clinical pregnancy and live birth rate, hence no definitive conclusions can be made. However, so far there appears to be no impact of the technique itself on success rates.
Topics: Azoospermia; Female; Humans; Male; Pregnancy; Pregnancy Rate; Sperm Retrieval
PubMed: 17895238
DOI: 10.1093/humupd/dmm029