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Male Fertility: New Horizons for Investigating Reproductive System Diseases
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Male Fertility: New Horizons for Investigating Reproductive System Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 October 2022) | Viewed by 22356

Special Issue Editor

Prof. Dr. Chuen Yan Cheng

E-Mail Website
Guest Editor
Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China
Previous Address: Population Council Headquarters, New York, NY, USA
Interests: human spermatogenesis; bioinformatics; biology spermatogenesis; non-obstructive azoospermia

Special Issue Information

Dear Colleagues,

In the last decade, there have been unprecedented advances in research on reproductive system diseases that impact male fertility, largely thanks to developments in biotechnology. These include techniques such as scRNA-Seq-based transcriptome profiling, 3D genome structural analysis and spatial transcriptome atlas of testes at near-single-cell resolution, and other high-resolution techniques. In this Special Issue, we seek to provide up-to-date reviews of advances in reproductive system diseases; thought-provoking conceptualizations of their biology and etiology; and research on the treatment of reproductive diseases. We also seek to better understand the challenges that we are facing in terms of infertility, and diseases of the testis, the epididymis, and the prostate, which collectively impact the status of fertility in humans.

This collection of review articles from a diverse group of active basic research scientists and clinicians/scientists will appeal to both senior investigators and those early in their career.

Prof. Dr. Chuen Yan Cheng
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • male fertility
  • reproductive system diseases
  • testis
  • epididymis
  • prostate male infertility
  • bioinformatics
  • singe cell-omics era
  • spermatogonial stem cells
  • androgen
  • meiosis

Published Papers (6 papers)

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Review

25 pages, 2291 KiB  
Review
Complementing Testicular Immune Regulation: The Relationship between Sertoli Cells, Complement, and the Immune Response
by Rachel L. Washburn and Jannette M. Dufour
Int. J. Mol. Sci. 2023, 24(4), 3371; https://doi.org/10.3390/ijms24043371 - 8 Feb 2023
Cited by 4 | Viewed by 4099
Abstract
Sertoli cells within the testis are instrumental in providing an environment for spermatogenesis and protecting the developing germ cells from detrimental immune responses which could affect fertility. Though these immune responses consist of many immune processes, this review focuses on the understudied complement [...] Read more.
Sertoli cells within the testis are instrumental in providing an environment for spermatogenesis and protecting the developing germ cells from detrimental immune responses which could affect fertility. Though these immune responses consist of many immune processes, this review focuses on the understudied complement system. Complement consists of 50+ proteins including regulatory proteins, immune receptors, and a cascade of proteolytic cleavages resulting in target cell destruction. In the testis, Sertoli cells protect the germ cells from autoimmune destruction by creating an immunoregulatory environment. Most studies on Sertoli cells and complement have been conducted in transplantation models, which are effective in studying immune regulation during robust rejection responses. In grafts, Sertoli cells survive activated complement, have decreased deposition of complement fragments, and express many complement inhibitors. Moreover, the grafts have delayed infiltration of immune cells and contain increased infiltration of immunosuppressive regulatory T cells as compared to rejecting grafts. Additionally, anti-sperm antibodies and lymphocyte infiltration have been detected in up to 50% and 30% of infertile testes, respectively. This review seeks to provide an updated overview of the complement system, describe its relationship with immune cells, and explain how Sertoli cells may regulate complement in immunoprotection. Identifying the mechanism Sertoli cells use to protect themselves and germ cells against complement and immune destruction is relevant for male reproduction, autoimmunity, and transplantation. Full article
(This article belongs to the Special Issue Male Fertility: New Horizons for Investigating Reproductive System Diseases)
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20 pages, 636 KiB  
Review
Functions of Steroid Hormones in the Male Reproductive Tract as Revealed by Mouse Models
by William H. Walker and Paul S. Cooke
Int. J. Mol. Sci. 2023, 24(3), 2748; https://doi.org/10.3390/ijms24032748 - 1 Feb 2023
Cited by 11 | Viewed by 2765
Abstract
Steroid hormones are capable of diffusing through cell membranes to bind with intracellular receptors to regulate numerous physiological processes. Three classes of steroid hormones, namely androgens, estrogens and glucocorticoids, contribute to the development of the reproductive system and the maintenance of fertility. During [...] Read more.
Steroid hormones are capable of diffusing through cell membranes to bind with intracellular receptors to regulate numerous physiological processes. Three classes of steroid hormones, namely androgens, estrogens and glucocorticoids, contribute to the development of the reproductive system and the maintenance of fertility. During the past 30 years, mouse models have been produced in which the expression of genes encoding steroid hormone receptors has been enhanced, partially compromised or eliminated. These mouse models have revealed many of the physiological processes regulated by androgens, estrogens and to a more limited extent glucocorticoids in the testis and male accessory organs. In this review, advances provided by mouse models that have facilitated a better understanding of the molecular regulation of testis and reproductive tract processes by steroid hormones are discussed. Full article
(This article belongs to the Special Issue Male Fertility: New Horizons for Investigating Reproductive System Diseases)
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30 pages, 1014 KiB  
Review
Sperm DNA Damage and Its Relevance in Fertility Treatment: A Review of Recent Literature and Current Practice Guidelines
by Jessica A. Marinaro and Peter N. Schlegel
Int. J. Mol. Sci. 2023, 24(2), 1446; https://doi.org/10.3390/ijms24021446 - 11 Jan 2023
Cited by 17 | Viewed by 3815
Abstract
Sperm deoxyribonucleic acid (DNA) damage has recently emerged as one of the most controversial topics in male reproductive medicine. While level I evidence indicates that abnormal sperm DNA damage has substantial adverse effects on reproductive outcomes (including chance of pregnancy and risk of [...] Read more.
Sperm deoxyribonucleic acid (DNA) damage has recently emerged as one of the most controversial topics in male reproductive medicine. While level I evidence indicates that abnormal sperm DNA damage has substantial adverse effects on reproductive outcomes (including chance of pregnancy and risk of miscarriage), there is limited consensus on how sperm DNA fragmentation (SDF) testing should be performed and/or interpreted in clinical practice. In this article, we review: (1) how SDF is assessed, (2) cumulative evidence regarding its impact on reproductive outcomes, (3) methods for mitigating high SDF, and (4) the most recent practice guidelines available for clinicians regarding the use and interpretation of SDF testing. Full article
(This article belongs to the Special Issue Male Fertility: New Horizons for Investigating Reproductive System Diseases)
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17 pages, 1286 KiB  
Review
CXADR: From an Essential Structural Component to a Vital Signaling Mediator in Spermatogenesis
by Yang Zhang and Wing-Yee Lui
Int. J. Mol. Sci. 2023, 24(2), 1288; https://doi.org/10.3390/ijms24021288 - 9 Jan 2023
Cited by 2 | Viewed by 1903
Abstract
Canonical coxsackievirus and adenovirus receptor (CXADR) is a transmembrane component of cell junctions that is crucial for cardiac and testicular functions via its homophilic and heterophilic interaction. CXADR is expressed in both Sertoli cells and germ cells and is localized mainly at the [...] Read more.
Canonical coxsackievirus and adenovirus receptor (CXADR) is a transmembrane component of cell junctions that is crucial for cardiac and testicular functions via its homophilic and heterophilic interaction. CXADR is expressed in both Sertoli cells and germ cells and is localized mainly at the interface between Sertoli-Sertoli cells and Sertoli-germ cells. Knockout of CXADR in mouse Sertoli cells specifically impairs male reproductive functions, including a compromised blood-testis barrier, apoptosis of germ cells, and premature loss of spermatids. Apart from serving as an important component for cell junctions, recent progress has showed the potential roles of CXADR as a signaling mediator in spermatogenesis. This review summarizes current research progress related to the regulation and role of CXADR in spermatogenesis as well as in pathological conditions. We hope this review provides some future directions and a blueprint to promote the further study on the roles of CXADR. Full article
(This article belongs to the Special Issue Male Fertility: New Horizons for Investigating Reproductive System Diseases)
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18 pages, 361 KiB  
Review
The Sperm Small RNA Transcriptome: Implications beyond Reproductive Disorder
by Sze Yan Chan, Crystal Wing Tung Wan, Tin Yu Samuel Law, David Yiu Leung Chan and Ellis Kin Lam Fok
Int. J. Mol. Sci. 2022, 23(24), 15716; https://doi.org/10.3390/ijms232415716 - 11 Dec 2022
Cited by 2 | Viewed by 2473
Abstract
Apart from the paternal half of the genetic material, the male gamete carries assorted epigenetic marks for optimal fertilization and the developmental trajectory for the early embryo. Recent works showed dynamic changes in small noncoding RNA (sncRNA) in spermatozoa as they transit through [...] Read more.
Apart from the paternal half of the genetic material, the male gamete carries assorted epigenetic marks for optimal fertilization and the developmental trajectory for the early embryo. Recent works showed dynamic changes in small noncoding RNA (sncRNA) in spermatozoa as they transit through the testicular environment to the epididymal segments. Studies demonstrated the changes to be mediated by epididymosomes during the transit through the adluminal duct in the epididymis, and the changes in sperm sncRNA content stemmed from environmental insults significantly altering the early embryo development and predisposing the offspring to metabolic disorders. Here, we review the current knowledge on the establishment of the sperm sncRNA transcriptome and their role in male-factor infertility, evidence of altered offspring health in response to the paternal life experiences through sperm sncRNA species and, finally, their implications in assisted reproductive technology in terms of epigenetic inheritance. Full article
(This article belongs to the Special Issue Male Fertility: New Horizons for Investigating Reproductive System Diseases)
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Graphical abstract

13 pages, 774 KiB  
Review
New Insights into Testosterone Biosynthesis: Novel Observations from HSD17B3 Deficient Mice
by Ben M. Lawrence, Liza O’Donnell, Lee B. Smith and Diane Rebourcet
Int. J. Mol. Sci. 2022, 23(24), 15555; https://doi.org/10.3390/ijms232415555 - 8 Dec 2022
Cited by 8 | Viewed by 6543
Abstract
Androgens such as testosterone and dihydrotestosterone (DHT) are essential for male sexual development, masculinisation, and fertility. Testosterone is produced via the canonical androgen production pathway and is essential for normal masculinisation and testis function. Disruption to androgen production can result in disorders of [...] Read more.
Androgens such as testosterone and dihydrotestosterone (DHT) are essential for male sexual development, masculinisation, and fertility. Testosterone is produced via the canonical androgen production pathway and is essential for normal masculinisation and testis function. Disruption to androgen production can result in disorders of sexual development (DSD). In the canonical pathway, 17β-hydroxysteroid dehydrogenase type 3 (HSD17B3) is viewed as a critical enzyme in the production of testosterone, performing the final conversion required. HSD17B3 deficiency in humans is associated with DSD due to low testosterone concentration during development. Individuals with HSD17B3 mutations have poorly masculinised external genitalia that can appear as ambiguous or female, whilst having internal Wolffian structures and testes. Recent studies in mice deficient in HSD17B3 have made the surprising finding that testosterone production is maintained, male mice are masculinised and remain fertile, suggesting differences between mice and human testosterone production exist. We discuss the phenotypic differences observed and the possible other pathways and enzymes that could be contributing to testosterone production and male development. The identification of alternative testosterone synthesising enzymes could inform the development of novel therapies to endogenously regulate testosterone production in individuals with testosterone deficiency. Full article
(This article belongs to the Special Issue Male Fertility: New Horizons for Investigating Reproductive System Diseases)
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