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Recent Advances and Future Perspectives of Male Reproduction: A Molecular Insight

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (31 January 2023) | Viewed by 15180

Special Issue Editors

Dr. Suresh C. Sikka

E-Mail Website
Guest Editor
Department of Urology, Tulane University School of Medicine, New Orleans, LA 70112, USA
Interests: male reproduction and erectile dysfunction (including penile doppler ultrasound); understanding the role of oxidative stress and aging as related to many urological disorders (mainly erectile dysfunction, infertility, GUI); their early detection and prevention employing specific molecular markers, stem-cells, in-vivo and in-vitro models
Special Issues, Collections and Topics in MDPI journals
Dr. Manesh Kumar Panner Selvam

E-Mail Website
Co-Guest Editor
Department of Urology, Tulane University School of Medicine, New Orleans, LA 70112, USA
Interests: reproductive medicine; sperm and seminal plamsa proteomics; applied bioinformatics; telomere signaling pathway; seminal exosome dysfunction; COVID and male reproduction; andrology; sperm DNA damage; seminal oxidative stress; testicular cancer; varicocele
Special Issues, Collections and Topics in MDPI journals
Dr. Omer A. Raheem

E-Mail Website
Co-Guest Editor
Assistant Professor of Surgery and Urology, The University of Chicago Medical Center, Pritzker School of Medicine, Chicago, IL 60637, USA
Interests: male infertility; erectile dysfunction; Peyronie’s disease; hypogonadism; overactive bladder (OAB); benign prostatic hyperplasia; urinary incontinence; LGBTQ health; voiding dysfunction; penile implants; artificial urinary sphincters; ejaculatory dysfunction; recurrent priapism; testicular sperm mapping; microsurgical testicular sperm retrieval; testicular sperm aspiration; transurethral resection of ejaculatory duct; vasectomy; microsurgical vasectomy reversal; enlarged prostate; testicular pain; testicular implants; genital dysphoria
Dr. Saradha Baskaran

E-Mail Website
Co-Guest Editor
School of Medicine, Tulane University, New Orleans, LA 70112, USA
Interests: reproductive toxicology; andrology; endocrine disruptors; oxidative stress; antioxidants; apoptosis; sperm DNA damage; sperm and seminal plasma proteomics; epigenetics

Special Issue Information

Dear Colleagues,

Reproductive health is central to men's physical, mental, emotional, and social well-being. Any deviation from the physiological function of male reproductive organs can have a direct or indirect negative impact on the reproductive outcome. The etiologies associated with male reproductive impairment are multifactorial and diverse, including bioenvironmental issues. The most common issues with male reproductive health are male infertility and sexual dysfunction. Nearly 20–30% of infertility problems occur due to abnormalities or defects in the male reproductive organs. Assisted reproductive techniques are used worldwide in the management of male infertility to improve the reproductive outcomes, despite their low success rates, which can be due to certain molecular changes at the subcellular level. It is also critical to understand the molecular factors and associated mechanisms regulating the physiology and pathophysiology of male reproductive organs. Recently, male reproductive research has gained more attention and shown substantial advancements. This Special Issue on “Recent Advances and Future Perspectives of Male Reproduction: A Molecular Insight” will feature the articles related to male reproductive research advancements, with insights at the molecular level. For this issue, we invite you and your colleagues to submit an original research article or comprehensive review article related to this field.

Dr. Suresh C. Sikka
Dr. Manesh Kumar Panner Selvam
Dr. Omer A. Raheem
Dr. Saradha Baskaran
Guest Editors

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

  • testis
  • sperm
  • seminal plasma
  • spermatogenesis
  • fertilization
  • proteomics
  • genomics
  • transcriptomics
  • miRNA
  • coding and non-coding RNAs
  • metabolomics
  • telomere
  • DNA damage and repair
  • post-translational modifications
  • apoptosis
  • molecular genetics
  • epigenetics
  • reproductive toxicity
  • toxicogenomics
  • endocrine disruptors
  • reproductive toxicants
  • varicocele
  • male infertility
  • sexual dysfunction
  • testicular cancer
  • erectile dysfunction
  • hypogonadism
  • obesity
  • lifestyle
  • infertility management
  • ART

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Published Papers (4 papers)

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Research

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18 pages, 2176 KiB  
Article
Testis-Specific Protein Y-Encoded (TSPY) Is Required for Male Early Embryo Development in Bos taurus
by Na-Young Rho, Teresa Mogas, W. Allan King and Laura A. Favetta
Int. J. Mol. Sci. 2023, 24(4), 3349; https://doi.org/10.3390/ijms24043349 - 8 Feb 2023
Cited by 2 | Viewed by 2648
Abstract
TSPY is a highly conserved multi-copy gene with copy number variation (CNV) among species, populations, individuals and within families. TSPY has been shown to be involved in male development and fertility. However, information on TSPY in embryonic preimplantation stages is lacking. This study [...] Read more.
TSPY is a highly conserved multi-copy gene with copy number variation (CNV) among species, populations, individuals and within families. TSPY has been shown to be involved in male development and fertility. However, information on TSPY in embryonic preimplantation stages is lacking. This study aims to determine whether TSPY CNV plays a role in male early development. Using sex-sorted semen from three different bulls, male embryo groups referred to as 1Y, 2Y and 3Y, were produced by in vitro fertilization (IVF). Developmental competency was assessed by cleavage and blastocyst rates. Embryos at different developmental stages were analyzed for TSPY CN, mRNA and protein levels. Furthermore, TSPY RNA knockdown was performed and embryos were assessed as per above. Development competency was only significantly different at the blastocyst stage, with 3Y being the highest. TSPY CNV and transcripts were detected in the range of 20–75 CN for 1Y, 20–65 CN for 2Y and 20–150 CN for 3Y, with corresponding averages of 30.2 ± 2.5, 33.0 ± 2.4 and 82.3 ± 3.6 copies, respectively. TSPY transcripts exhibited an inverse logarithmic pattern, with 3Y showing significantly higher TSPY. TSPY proteins, detected only in blastocysts, were not significantly different among groups. TSPY knockdown resulted in a significant TSPY depletion (p < 0.05), with no development observed after the eight-cell stage in male embryos, suggesting that TSPY is required for male embryo development. Full article
(This article belongs to the Special Issue Recent Advances and Future Perspectives of Male Reproduction: A Molecular Insight)
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17 pages, 10564 KiB  
Article
Single-Cell Transcriptomic Profiling of the Mouse Testicular Germ Cells Reveals Important Role of Phosphorylated GRTH/DDX25 in Round Spermatid Differentiation and Acrosome Biogenesis during Spermiogenesis
by Raghuveer Kavarthapu, Rajakumar Anbazhagan, Soumitra Pal and Maria L. Dufau
Int. J. Mol. Sci. 2023, 24(4), 3127; https://doi.org/10.3390/ijms24043127 - 4 Feb 2023
Cited by 6 | Viewed by 3367
Abstract
Gonadotropin-regulated testicular RNA helicase (GRTH)/DDX25 is a member of DEAD-box family of RNA helicase essential for the completion of spermatogenesis and male fertility, as evident from GRTH-knockout (KO) mice. In germ cells of male mice, there are two species of GRTH, a 56 [...] Read more.
Gonadotropin-regulated testicular RNA helicase (GRTH)/DDX25 is a member of DEAD-box family of RNA helicase essential for the completion of spermatogenesis and male fertility, as evident from GRTH-knockout (KO) mice. In germ cells of male mice, there are two species of GRTH, a 56 kDa non-phosphorylated form and 61 kDa phosphorylated form (pGRTH). GRTH Knock-In (KI) mice with R242H mutation abolished pGRTH and its absence leads to infertility. To understand the role of the GRTH in germ cell development at different stages during spermatogenesis, we performed single-cell RNA-seq analysis of testicular cells from adult WT, KO and KI mice and studied the dynamic changes in gene expression. Pseudotime analysis revealed a continuous developmental trajectory of germ cells from spermatogonia to elongated spermatids in WT mice, while in both KO and KI mice the trajectory was halted at round spermatid stage indicating incomplete spermatogenesis process. The transcriptional profiles of KO and KI mice were significantly altered during round spermatid development. Genes involved in spermatid differentiation, translation process and acrosome vesicle formation were significantly downregulated in the round spermatids of KO and KI mice. Ultrastructure of round spermatids of KO and KI mice revealed several abnormalities in acrosome formation that includes failure of pro-acrosome vesicles to fuse to form a single acrosome vesicle, and fragmentation of acrosome structure. Our findings highlight the crucial role of pGRTH in differentiation of round spermatids into elongated spermatids, acrosome biogenesis and its structural integrity. Full article
(This article belongs to the Special Issue Recent Advances and Future Perspectives of Male Reproduction: A Molecular Insight)
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15 pages, 2457 KiB  
Article
Disruptions in Hypothalamic–Pituitary–Gonadal Axis Development and Their IgG Modulation after Prenatal Systemic Inflammation in Male Rats
by Vasilina Ignatiuk, Marina Izvolskaia, Viktoria Sharova and Liudmila Zakharova
Int. J. Mol. Sci. 2023, 24(3), 2726; https://doi.org/10.3390/ijms24032726 - 1 Feb 2023
Cited by 15 | Viewed by 3076
Abstract
The development of the neuroendocrine system, including the hypothalamic–pituitary–gonadal (HPG) axis, is sensitive to environmental impacts during critical developmental periods. Maternal immune system activation by bacterial or viral infection may be one of the negative impacts. This study focused on the effect of [...] Read more.
The development of the neuroendocrine system, including the hypothalamic–pituitary–gonadal (HPG) axis, is sensitive to environmental impacts during critical developmental periods. Maternal immune system activation by bacterial or viral infection may be one of the negative impacts. This study focused on the effect of systemic inflammation induced by lipopolysaccharides (LPS E. coli) on the HPG axis development in male rat offspring, corrected by the anti-inflammatory action of polyclonal IgG and monoclonal anti-interleukin (IL)-6 receptor antibodies (IL-6RmAbs). A single LPS exposure on the 12th embryonic day (ED) led to a decrease in the number of afferent synaptic inputs on gonadotropin-releasing, hormone-producing neurons in adult male offspring. LPS exposure on ED18 did not lead to such disruptions. Moreover, after the LPS injections on ED12, circulating follicle-stimulating hormone and sex steroid levels were reduced, and the gonadal structure was disrupted. A prenatal IL-6R blockade with IL-6RmAbs and polyclonal IgG reduced the negative effects of inflammation on fetal HPG axis development. Overall, the data obtained confirm the morphogenetic effect of inflammation on fetal HPG development and IL-6 involvement in these processes. Full article
(This article belongs to the Special Issue Recent Advances and Future Perspectives of Male Reproduction: A Molecular Insight)
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Review

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17 pages, 1127 KiB  
Review
Reactive Nitrogen Species and Male Reproduction: Physiological and Pathological Aspects
by Sulagna Dutta, Pallav Sengupta, Sanghamitra Das, Petr Slama and Shubhadeep Roychoudhury
Int. J. Mol. Sci. 2022, 23(18), 10574; https://doi.org/10.3390/ijms231810574 - 12 Sep 2022
Cited by 23 | Viewed by 4165
Abstract
Reactive nitrogen species (RNS), like reactive oxygen species (ROS), are useful for sustaining reproductive processes such as cell signaling, the regulation of hormonal biosynthesis, sperm capacitation, hyperactivation, and acrosome reaction. However, endogenous levels of RNS beyond physiological limits can impair fertility by disrupting [...] Read more.
Reactive nitrogen species (RNS), like reactive oxygen species (ROS), are useful for sustaining reproductive processes such as cell signaling, the regulation of hormonal biosynthesis, sperm capacitation, hyperactivation, and acrosome reaction. However, endogenous levels of RNS beyond physiological limits can impair fertility by disrupting testicular functions, reducing gonadotropin production, and compromising semen quality. Excessive RNS levels cause a variety of abnormalities in germ cells and gametes, particularly in the membranes and deoxyribonucleic acid (DNA), and severely impair the maturation and fertilization processes. Cell fragmentation and developmental blockage, usually at the two-cell stage, are also connected with imbalanced redox status of the embryo during its early developmental stage. Since high RNS levels are closely linked to male infertility and conventional semen analyses are not reliable predictors of the assisted reproductive technology (ART) outcomes for such infertility cases, it is critical to develop novel ways of assessing and treating oxidative and/or nitrosative stress-mediated male infertility. This review aims to explicate the physiological and pathological roles of RNS and their relationship with male reproduction. Full article
(This article belongs to the Special Issue Recent Advances and Future Perspectives of Male Reproduction: A Molecular Insight)
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