Male Infertility Update: Current Knowledge on Etiology, Comorbidities, Diagnosis and Treatment: Preclinical Topics

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Reproductive Cells and Development".

Deadline for manuscript submissions: 30 June 2025 | Viewed by 4467

Special Issue Editors


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Guest Editor
Andrology, Female Endocrinology and Gender Incongruence Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy
Interests: andrology; male genital tract ultrasound; male infertility; sexual dysfunction; erectile dysfunction; premature ejaculation
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Guest Editor
Endocrinology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy
Interests: testosterone; hormonal analysis; reproductive biology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Infertility affects up to 12% of all men and represents a growing health problem. To date, its etiology is known in half of cases, while in the other half, it is still obscure. The known causes of infertility can be related to congenital or acquired conditions acting at a pre-testicular, testicular or post-testicular level. Genetic abnormalities account for ~15% of all causes, while epigenetic modifications, oxidative stress, immunological mechanisms and advanced paternal age are increasingly studied as possible co-factors. Systemic diseases, environmental and lifestyle factors and some medications can affect male reproductive health. On the other hand, infertility is nowadays considered as a proxy of general male health, and can lead to psychological and sexual dysfunctions. The recent advances in the understanding of male infertility include efforts in the fields of genetics, sperm biology and male genital tract ultrasound. Conventional and unconventional semen parameters as well as hormonal, metabolic and microbial parameters are used to understand and categorize male infertility etiology and as decisional reference points to define a therapeutic strategy for the infertile man. Medical and surgical therapy can help in specific conditions to improve semen quality, promoting the chances of a natural or medically assisted pregnancy. Personalized medicine and preventive strategies in male infertility are advocated, as well as the evaluation and management of both male and female partners in infertile couples.

You may choose our Joint Special Issue in JCM.

Prof. Dr. Francesco Lotti
Prof. Dr. Mario Maggi
Guest Editors

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Keywords

  • male infertility
  • diagnosis
  • treatment
  • etiology
  • pre-testicular/testicular/post-testicular causes
  • genetic causes
  • seminal parameters
  • hormonal parameters
  • ultrasound
  • general health
  • azoospermia

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Published Papers (3 papers)

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Research

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16 pages, 5499 KiB  
Article
Transcriptomic Differences by RNA Sequencing for Evaluation of New Method for Long-Time In Vitro Culture of Cryopreserved Testicular Tissue for Oncologic Patients
by Cheng Pei, Plamen Todorov, Qingduo Kong, Mengyang Cao, Evgenia Isachenko, Gohar Rahimi, Frank Nawroth, Nina Mallmann-Gottschalk, Wensheng Liu and Volodimir Isachenko
Cells 2024, 13(18), 1539; https://doi.org/10.3390/cells13181539 - 13 Sep 2024
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Abstract
Background: Earlier studies have established that culturing human ovarian tissue in a 3D system with a small amount of soluble Matrigel (a basement membrane protein) for 7 days in vitro increased gene fusion and alternative splicing events, cellular functions, and potentially impacted gene [...] Read more.
Background: Earlier studies have established that culturing human ovarian tissue in a 3D system with a small amount of soluble Matrigel (a basement membrane protein) for 7 days in vitro increased gene fusion and alternative splicing events, cellular functions, and potentially impacted gene expression. However, this method was not suitable for in vitro culture of human testicular tissue. Objective: To test a new method for long-time in vitro culture of testicular fragments, thawed with two different regimes, with evaluation of transcriptomic differences by RNA sequencing. Methods: Testicular tissue samples were collected, cryopreserved (frozen and thawed), and evaluated immediately after thawing and following one week of in vitro culture. Before in vitro culture, tissue fragments were encapsulated in fibrin. Four experimental groups were formed. Group 1: tissue quickly thawed (in boiling water at 100 °C) and immediately evaluated. Group 2: tissue quickly thawed (in boiling water at 100 °C) and evaluated after one week of in vitro culture. Group 3: tissue slowly thawed (by a physiological temperature 37 °C) and immediately evaluated. Group 4: tissue slowly thawed (by a physiological temperature 37 °C) and evaluated after one week of in vitro culture. Results: There are the fewest differentially expressed genes in the comparison between Group 2 and Group 4. In this comparison, significantly up-regulated genes included C4B_2, LOC107987373, and GJA4, while significantly down-regulated genes included SULT1A4, FBLN2, and CCN2. Differential genes in cells of Group 2 were mainly enriched in KEGG: regulation of actin cytoskeleton, lysosome, proteoglycans in cancer, TGF-beta signaling pathway, focal adhesion, and endocytosis. These Group 2- genes were mainly enriched in GO: spermatogenesis, cilium movement, collagen fibril organization, cell differentiation, meiotic cell cycle, and flagellated spermatozoa motility. Conclusions: Encapsulation of testicular tissue in fibrin and long-time in vitro culture with constant stirring in a large volume of culture medium can reduce the impact of thawing methods on cryopreserved testicular tissue. Full article
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15 pages, 1297 KiB  
Article
Sperm Concentration Improvement May Be a Parameter Predicting Efficacy of FSH Therapy of Male Idiopathic Infertility
by Daniele Santi, Giorgia Spaggiari, Leonardo Dalla Valentina, Marilina Romeo, Federico Nuzzo, Lorenzo Serlenga, Laura Roli, Maria Cristina De Santis, Tommaso Trenti, Antonio R. M. Granata and Manuela Simoni
Cells 2023, 12(18), 2236; https://doi.org/10.3390/cells12182236 - 8 Sep 2023
Cited by 1 | Viewed by 1420
Abstract
Testis stimulation with follicle-stimulating hormone (FSH) is one of the empirical treatments proposed for male idiopathic infertility, although reliable markers to predict its efficacy are still lacking. This study aimed to identify parameters able to predict FSH efficacy in terms of pregnancy achievement. [...] Read more.
Testis stimulation with follicle-stimulating hormone (FSH) is one of the empirical treatments proposed for male idiopathic infertility, although reliable markers to predict its efficacy are still lacking. This study aimed to identify parameters able to predict FSH efficacy in terms of pregnancy achievement. A real-world study was conducted, enrolling idiopathic infertile men treated with FSH 150IU three times weekly. Patients were treated until pregnancy achievement or for a maximum of two years and two visits were considered: V0 (baseline) and V1 (end of FSH treatment). Primary endpoints were the V1-V0 percentage change in sperm concentration, total sperm count, and total motile sperm number. In total, 48 pregnancies were recorded (27.7%) among 173 men (age 37.9 ± 6.2 years). All three endpoints increased after FSH administration, and only the V1-V0 percentage of sperm concentration significantly predicted pregnancy (p = 0.007). A V1-V0 sperm concentration of 30.8% predicted pregnancy, and the sperm concentration V1-V0 percentage (Y) required to obtain a pregnancy was predicted according to its baseline values (x): Y = 9.8433x2 − 203.67x + 958.29. A higher number of pregnancies was reached in men with baseline sperm concentration below 7.3 million/mL. Thus, the percentage of sperm concentration increasing after FSH administration could predict the treatment efficacy in terms of pregnancy. At the dosage used, the efficacy was significantly higher in patients with a starting sperm concentration < 7.3 mill/mL. Mathematical analyses identified a function able to predict the sperm concentration increase required to obtain a pregnancy in relation to the baseline sperm number. Full article
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Review

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12 pages, 583 KiB  
Review
Male Tract Microbiota and Male Infertility
by Giuseppe Grande, Andrea Graziani, Luca De Toni, Andrea Garolla and Alberto Ferlin
Cells 2024, 13(15), 1275; https://doi.org/10.3390/cells13151275 - 29 Jul 2024
Cited by 1 | Viewed by 1433
Abstract
In recent years, several studies have analyzed the composition of the male genital tract microbiota and its changes in infertility or in different situations associated with infertility. The aim of this narrative review is to obtain more insight on this topic; in particular, [...] Read more.
In recent years, several studies have analyzed the composition of the male genital tract microbiota and its changes in infertility or in different situations associated with infertility. The aim of this narrative review is to obtain more insight on this topic; in particular, to describe actual evidence about changes in the semen microbiota in patients with infertility, male tract infections, or HPV infections. In semen, an increase in semen Prevotella spp. is associated with oligozoospermia and with obesity-associated asthenozoospermia; an increase in Pseudomonas is more frequently associated with asthenozoospermia and oligozoospermia; a reduction in Lactobacilli spp. (namely in Lactobacillus crispatus) may represent a marker of low semen quality. However, an increase in Lactobacillus iners is considered a risk factor for a reduced sperm concentration. In patients with prostatitis, there is a reduction in Lactobacillus spp. and an increase in Streptococcus spp., opening important perspectives about the role of probiotic treatments in these patients. Finally, an increase in Fusobacteria spp. was observed in patients with an HPV infection. In the conclusion, we underline the interactions between the seminal and vaginal microbiota, so that further studies should focus on the “couple genital microbiota”. Full article
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