Clinical Trends and Novel Research Insights in Testicular and Penile Disorders and Infertility

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Medical Research".

Deadline for manuscript submissions: 20 May 2024 | Viewed by 14807

Special Issue Editor


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Guest Editor
1. Clinic of Urology, University Clinical Center of Serbia, 11000 Belgrade, Serbia
2. Faculty of Medicine, University of Belgrade,11000 Belgrade, Serbia
Interests: testicular cancer; urologic oncology; BPH; urolithiasis

Special Issue Information

Dear Colleagues,

Disorders that affect the external male genitalia are numerous and feature broad-spectrum entities, ranging from painless to disabling, and from benign to malignant. The extraordinary heterogeneity in terms of pathobiology, epidemiological trends, clinical presentation, and severity coupled with the diversity of available preventive and curative approaches, treatment effectiveness, potential complications, and adverse effects shape the complex and intriguing scientific and practical landscape in this constantly evolving area of urology.

The magnitude of public health burden related to testicular and penile non-neoplastic conditions (including testicular trauma and torsion, orchitis and epididymitis, hydrocele, spermatocele, hypogonadism, penile trauma, erectile dysfunction, priapism, Peyronie’s disease, balanitis, urethral diseases and penile and urethral anomalies), respective oncopathologies (i.e. testicular and penile cancer), and infertility underpin the need for research efforts and knowledge dissemination that will inspire innovations, inform novel clinical trends, amplify patient centricity, and provide guidance for the advancement in this field.

This Special Issue will collate high-quality fundamental, clinical and translational research, as well as in-depth reviews, aiming to foster debate on new scientific insights, clinical trends, current challenges, and future perspectives compliant with this comprehensive topic. 

Dr. Uroš Bumbaširević
Guest Editor

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Keywords

  • testicular cancer
  • penile cancer
  • penile disorders
  • testicular disorders
  • infertility
  • erectile dysfunction
  • Peyronie’s disease

Published Papers (9 papers)

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Research

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12 pages, 12900 KiB  
Article
Isolated Male Epispadias Repair: Long-Term Outcomes
by Marko Bencic, Marta Bizic, Ivana Joksic, Borko Stojanovic and Miroslav L. Djordjevic
Life 2024, 14(4), 446; https://doi.org/10.3390/life14040446 - 28 Mar 2024
Viewed by 446
Abstract
Isolated male epispadias is one of the most severe congenital genital anomalies that require surgical correction. The goals of the surgery are to reach good aesthetic and functional outcomes. The aim of this retrospective study was to analyze the long-term outcomes of surgical [...] Read more.
Isolated male epispadias is one of the most severe congenital genital anomalies that require surgical correction. The goals of the surgery are to reach good aesthetic and functional outcomes. The aim of this retrospective study was to analyze the long-term outcomes of surgical reconstruction of male epispadias. A total of 31 patients with a mean age of 17 years, who underwent surgical repair of isolated male epispadias from January 2000 to January 2015, were involved. The main outcome measures were defined as: aesthetic outcome, continence, postoperative complications, sexual function, and quality of life. The follow-up period ranged from 8 to 23 years, with an average of 14.4 years. Each patients underwent an average of 2.2 surgical procedures in this period. The most common postoperative complications were urethral fistula and residual curvature, in 22.6% and 12.9%, respectively. Satisfactory aesthetic outcome was reported in 71.4% of cases. The repair of male epispadias usually includes more than two procedures with satisfactory aesthetic outcome. Unsolved urinary incontinence remains a significant issue and has a high impact on the quality of life. Follow-up should be extended even after complete sexual maturity. Comprehensive long-term evaluation is necessary for proper treatment of isolated epispadias. Full article
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14 pages, 5580 KiB  
Article
Penile Microdissection: A Live Donor Feasibility Study in Feminizing Gender-Affirming Surgery
by Slavica Pusica, Borko Stojanovic, Marko Bencic, Marta Bizic, Tatjana Atanasijevic and Miroslav L. Djordjevic
Life 2023, 13(11), 2212; https://doi.org/10.3390/life13112212 - 15 Nov 2023
Viewed by 1479
Abstract
Femininizing gender affirmation surgery includes the creation of external female genitalia such as a new clitoris, labia, and vagina with removal of the glans and urethral remnants and full corpora cavernosa. We evaluated the possibility of using preserved cavernosal bodies with glans and [...] Read more.
Femininizing gender affirmation surgery includes the creation of external female genitalia such as a new clitoris, labia, and vagina with removal of the glans and urethral remnants and full corpora cavernosa. We evaluated the possibility of using preserved cavernosal bodies with glans and urethral remnants for potential live-donor penile transplantation. Between March 2021 and February 2023, penile microvascular dissection followed by gender-affirming vaginoplasty was performed in 41 patients aged 18 to 57 years (mean 30.5 years). The mean follow-up was 15 months (ranging from 6 to 26 months). The removed penile entities were properly measured. The corpora cavernosa were completely preserved in all cases; the length of remaining anterior urethra ranged from 12.70 cm to 16.40 cm, while the mean glans remnant volume was 85.37% of the total volume. All patients reported satisfactory results after gender-affirming vaginoplasty. Microvascular penile dissection in gender-affirming vaginoplasty is simple and safe, suggesting a good possibility of using the full corpora cavernosa, glans, and anterior urethra remnants for live-donor penile transplantation. Full article
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20 pages, 1327 KiB  
Article
Understanding the Male Perspective: Evaluating Quality of Life and Psychological Distress in Serbian Men Undergoing Infertility Treatment
by Bojan Čegar, Sandra Šipetić Grujičić, Jovana Bjekić, Aleksandar Vuksanović, Nebojša Bojanić, Daniela Bartolović, Darko Jovanović and Milica Zeković
Life 2023, 13(9), 1894; https://doi.org/10.3390/life13091894 - 11 Sep 2023
Cited by 1 | Viewed by 933
Abstract
The experience of an infertility diagnosis and treatment imposes a profound burden on affected individuals, encompassing not only physical and medical aspects but also a plethora of psychological, social, and emotional factors. By employing a multimodal assessment featuring validated self-report questionnaires, physical measurements, [...] Read more.
The experience of an infertility diagnosis and treatment imposes a profound burden on affected individuals, encompassing not only physical and medical aspects but also a plethora of psychological, social, and emotional factors. By employing a multimodal assessment featuring validated self-report questionnaires, physical measurements, and clinical records, the present study aimed to explore the quality of life and psycho-emotional distress of men undergoing infertility treatment in Serbia, thereby addressing the dearth of research on the underrepresented male perspective in this domain. Findings revealed diverse semen abnormalities among participants (n = 96, average age 37.69 ± 5.72), with significant associations between longer treatment durations and reduced sperm motility. The observed rates of men surpassing predetermined DASS-42 questionnaire thresholds for depression, anxiety, and stress in the analyzed cohort were 13.54%, 11.46%, and 22.92%, respectively. Summary scores in conceptual areas comprised in the SF-36 questionnaire ranged from 49.00 ± 6.25 for the mental health dimension to 90.16 ± 17.75 obtained in the physical functioning subscale. Patients with a longer treatment duration demonstrated lower scores in the role emotional domain, indicative of a less favorable emotional state. Expectedly, inverse correlations were found between the SF-36 mental health score and DASS-42 subscales. By addressing the existing knowledge gap and highlighting the unique needs of infertile men, the finding of this study may contribute to a more inclusive and holistic approach to infertility research and management. Full article
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13 pages, 500 KiB  
Article
The Polymorphisms in GSTO Genes (GSTO1 rs4925, GSTO2 rs156697, and GSTO2 rs2297235) Affect the Risk for Testicular Germ Cell Tumor Development: A Pilot Study
by Milos Petrovic, Tatjana Simic, Tatjana Djukic, Tanja Radic, Ana Savic-Radojevic, Milica Zekovic, Otas Durutovic, Aleksandar Janicic, Bogomir Milojevic, Boris Kajmakovic, Marko Zivkovic, Nebojsa Bojanic, Uros Bumbasirevic and Vesna Coric
Life 2023, 13(6), 1269; https://doi.org/10.3390/life13061269 - 27 May 2023
Viewed by 1276
Abstract
Members of the omega class of glutathione transferases (GSTs), GSTO1, and GSTO2, catalyze a range of reduction reactions as a part of the antioxidant defense system. Polymorphisms of genes encoding antioxidant proteins and the resultant altered redox profile have already been associated with [...] Read more.
Members of the omega class of glutathione transferases (GSTs), GSTO1, and GSTO2, catalyze a range of reduction reactions as a part of the antioxidant defense system. Polymorphisms of genes encoding antioxidant proteins and the resultant altered redox profile have already been associated with the increased risk for testicular germ cell cancer (GCT) development. The aim of this pilot study was to assess the individual, combined, haplotype, and cumulative effect of GSTO1rs4925, GSTO2rs156697, and GSTO2rs2297235 polymorphisms with the risk for testicular GCT development, in 88 patients and 96 matched controls, through logistic regression models. We found that carriers of the GSTO1*C/A*C/C genotype exhibited an increased risk for testicular GCT development. Significant association with increased risk of testicular GCT was observed in carriers of GSTO2rs2297235*A/G*G/G genotype, and in carriers of combined GSTO2rs156697*A/G*G/G and GSTO2rs2297235*A/G*G/G genotypes. Haplotype H7 (GSTO1rs4925*C/GSTO2rs2297235*G/GSTO2rs156697*G) exhibited higher risk of testicular GCT, however, without significant association (p > 0.05). Finally, 51% of testicular GCT patients were the carriers of all three risk-associated genotypes, with 2.5-fold increased cumulative risk. In conclusion, the results of this pilot study suggest that GSTO polymorphisms might affect the protective antioxidant activity of GSTO isoenzymes, therefore predisposing susceptible individuals toward higher risk for testicular GCT development. Full article
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11 pages, 1299 KiB  
Article
DHX37 and NR5A1 Variants Identified in Patients with 46,XY Partial Gonadal Dysgenesis
by Felipe Rodrigues de Oliveira, Taís Nitsch Mazzola, Maricilda Palandi de Mello, Ana Paula Francese-Santos, Sofia Helena V. de Lemos-Marini, Andrea Trevas Maciel-Guerra, Olaf Hiort, Ralf Werner, Gil Guerra-Junior and Helena Fabbri-Scallet
Life 2023, 13(5), 1093; https://doi.org/10.3390/life13051093 - 27 Apr 2023
Cited by 1 | Viewed by 1411
Abstract
The group of disorders known as 46,XY gonadal dysgenesis (GD) is characterized by anomalies in testis determination, including complete and partial GD (PGD) and testicular regression syndrome (TRS). Several genes are known to be involved in sex development pathways, however approximately 50% of [...] Read more.
The group of disorders known as 46,XY gonadal dysgenesis (GD) is characterized by anomalies in testis determination, including complete and partial GD (PGD) and testicular regression syndrome (TRS). Several genes are known to be involved in sex development pathways, however approximately 50% of all cases remain elusive. Recent studies have identified variants in DHX37, a gene encoding a putative RNA helicase essential in ribosome biogenesis and previously associated with neurodevelopmental disorders, as a cause of PGD and TRS. To investigate the potential role of DHX37 in disorders of sexual development (DSD), 25 individuals with 46,XY DSD were analyzed and putative pathogenic variants were found in four of them. WES analyses were performed on these patients. In DHX37, the variant p.(Arg308Gln), recurrent associated with DSD, was identified in one patient; the p.(Leu467Val), predicted to be deleterious, was found together with an NR5A1 loss-of-function variant in patient 2; and, the p.(Val999Met) was identified in two unrelated patients, one of whom (patient 3) also carried a pathogenic NR5A1 variant. For both patients carrying DHX37 and NR5A1 pathogenic variants, a digenic inheritance is suggested. Our findings support the importance of DHX37 variants as a cause of disorders of sex development, implying a role in testis development. Full article
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10 pages, 628 KiB  
Article
Self-Reported Asthma Is Associated with Reduced Sperm Count—A Cross-Sectional Study of More than 6000 Young Men from the General Population
by Marc K. Pedersen, Elvira V. Bräuner, Ann H. Hansen, Laura S. Hansen, Tina K. Jensen, Niels Jørgensen and Lærke Priskorn
Life 2023, 13(2), 278; https://doi.org/10.3390/life13020278 - 19 Jan 2023
Viewed by 3793
Abstract
Asthma is driven by an inflammatory response that may impact testicular function. In this cross-sectional study, we investigated the association between self-reported asthma and testicular function (semen parameters, reproductive hormone levels), and determined whether potential further inflammation due to self-reported allergy modified this [...] Read more.
Asthma is driven by an inflammatory response that may impact testicular function. In this cross-sectional study, we investigated the association between self-reported asthma and testicular function (semen parameters, reproductive hormone levels), and determined whether potential further inflammation due to self-reported allergy modified this association. A total of 6177 men from the general population completed a questionnaire including information on doctor-diagnosed asthma or allergy, had a physical examination, delivered a semen sample, and had a blood sample drawn. Multiple linear regression analyses were performed. A total of 656 (10.6%) men reported having ever been diagnosed with asthma. Generally, self-reported asthma was consistently associated with a poorer testicular function; however, few estimates were statistically significant. Specifically, self-reported asthma was associated with statistically significant lower total sperm count [median: 133 vs. 145 million; adjusted β (95% CI): −0.18 (−0.33 to −0.04) million on cubic-root-transformed scale] and borderline statistically significant lower sperm concentration compared with no self-reported asthma. The association between asthma and total sperm count was of similar magnitude among men with and without allergy. In conclusion, men with self-reported asthma had poorer testicular function than men without asthma. However, the cross-sectional design of the study limits ascertainment of causality. Full article
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Review

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19 pages, 4721 KiB  
Review
The Global Decline in Human Fertility: The Post-Transition Trap Hypothesis
by Robert John Aitken
Life 2024, 14(3), 369; https://doi.org/10.3390/life14030369 - 11 Mar 2024
Viewed by 1083
Abstract
Over the past half a century many countries have witnessed a rapid fall in total fertility rates, particularly in the world’s most advanced economies including the industrial powerhouses of Eastern Asia and Europe. Such nations have now passed through the first and second [...] Read more.
Over the past half a century many countries have witnessed a rapid fall in total fertility rates, particularly in the world’s most advanced economies including the industrial powerhouses of Eastern Asia and Europe. Such nations have now passed through the first and second demographic transitions and are currently exhibiting fertility rates well below the replacement threshold of 2.1, with no sign of recovery. This paper examines the factors responsible for driving these demographic transitions and considers their impact on both fertility and fecundity (our fundamental capacity to reproduce). I argue that because the first demographic transition was extremely rapid and largely driven by socioeconomic factors, it has had no lasting impact on the genetic/epigenetic underpinnings of human fecundity. However, the second demographic transition will be different. A series of conditions associated with low fertility societies, including relaxed selection pressure for high-fertility genotypes, the indiscriminate use of assisted reproductive technologies to treat human infertility, and environmental contamination with reproductive toxicants, may impact our genetic constitution in ways that compromise the future fecundity of our species. Since any fundamental change in the genetic foundations of human reproduction will be difficult to reverse, we should actively pursue methods to monitor human fecundity, as sub-replacement fertility levels become established across the globe. Full article
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16 pages, 1069 KiB  
Review
Prognostic Significance of Systemic Inflammation Markers in Testicular and Penile Cancer: A Narrative Review of Current Literature
by Aleksandar Janicic, Milos Petrovic, Milica Zekovic, Nenad Vasilic, Vesna Coric, Bogomir Milojevic, Marko Zivkovic and Uros Bumbasirevic
Life 2023, 13(3), 600; https://doi.org/10.3390/life13030600 - 21 Feb 2023
Cited by 2 | Viewed by 1351
Abstract
In contemporary clinical practice, biomarkers are indispensable in the assessment and management of oncological patients. Although established serum tumor markers (beta human chorionic gonadotropin (bHCG), alpha fetoprotein (AFP), and lactate dehydrogenase (LDH)) have an indisputably important role in the management of patients with [...] Read more.
In contemporary clinical practice, biomarkers are indispensable in the assessment and management of oncological patients. Although established serum tumor markers (beta human chorionic gonadotropin (bHCG), alpha fetoprotein (AFP), and lactate dehydrogenase (LDH)) have an indisputably important role in the management of patients with testicular cancer (TC), the application of these tumor markers may be accompanied with certain limitations, implying the need for additional biomarkers. Contrary to TC, there is a lack of established serological biomarkers for penile cancer (PC) and the management of this urological malignancy is based on multiple clinicopathological parameters. Therefore, the identification and rigorous analytical and clinical validation of reliable biomarkers are considered pivotal for improving PC management. Inflammation may be associated with all stages of oncogenesis, from initial neoplastic transformation to angiogenesis, tissue invasion, and metastasis. Accordingly, an array of inflammation-related indices have gained increasing attention as emerging predictors of oncological outcomes. The clinical usefulness of systemic inflammation markers was reported in many urological and non-urological malignancies. The aim of this narrative review is to summarize current scientific data regarding the prognostic and predictive significance of systemic inflammation markers in TC and PC patients. Full article
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Other

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15 pages, 1249 KiB  
Systematic Review
Maternal Exposure to Cigarette Smoke during Pregnancy and Testicular Cancer in Offspring: A Systematic Review and Meta-Analysis
by Astrid L. Beck, Elvira V. Bräuner, Russ Hauser, Youn-Hee Lim, Cecilie S. Uldbjerg and Anders Juul
Life 2023, 13(3), 618; https://doi.org/10.3390/life13030618 - 23 Feb 2023
Cited by 2 | Viewed by 1727
Abstract
Background: Maternal exposure to cigarette smoke in pregnancy may play a role in the development of testicular cancer in offspring. An updated and comprehensive systematic review of the available evidence is needed. Objective: To identify and evaluate current evidence on maternal exposure to [...] Read more.
Background: Maternal exposure to cigarette smoke in pregnancy may play a role in the development of testicular cancer in offspring. An updated and comprehensive systematic review of the available evidence is needed. Objective: To identify and evaluate current evidence on maternal exposure to cigarette smoke during pregnancy and testicular cancer in offspring. Methods: A systematic search of English peer-reviewed original literature in PubMed through a block search approach. Publications were considered if assessing maternal exposure to cigarette smoke and the risk of testicular cancer in offspring. Results: Among the 636 identified records, 14 publications were eligible for review and 10 for meta-analysis. Quality assessment of the publications was conducted. Most included publications were case-control studies (n = 11, 79%), while the remaining were ecological studies (n = 3, 21%). Completeness of reporting was high, but more than half were considered subject to potential bias. The trend synthesis showed that half (n = 7) of the included publications demonstrated a higher risk of testicular cancer in the sons of mothers exposed to cigarette smoke during pregnancy. The meta-analysis generated an overall summary risk estimate of 1.00 (95% CI: 0.88; 1.15) (n = 10 publications), with a lower risk for seminoma (0.79, 95% CI: 0.59; 1.04) and nonseminoma (0.96, 95% CI: 0.74; 1.26) (n = 4 publications). Conclusions: This systematic review did not provide evidence of an association between maternal exposure to cigarette smoke and risk of testicular cancer in offspring. An overall positive trend was suggested, but it had low statistical precision. The methodological limitations across publications encourage further research based on valid exposure data. Full article
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