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Biomolecules
Special Issues
Cellular and Molecular Mechanism of Spermatogenesis
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Cellular and Molecular Mechanism of Spermatogenesis

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Reproduction".

Deadline for manuscript submissions: 10 May 2025 | Viewed by 4483

Special Issue Editor

Dr. Yanhe Lue

E-Mail Website
Guest Editor
Division of Endocrinology, The Lundquist Institute and Harbor-UCLA Medical Center, Torrance, CA 90502, USA
Interests: spermatogenesis regulation; spermatogonial stem cell; meiosis; spermiogenesis; sertoli cell; in vitro spermatogenesis

Special Issue Information

Dear Colleagues,

We are pleased to invite you to submit your manuscript to this Special Issue of “Cellular and Molecular Mechanism of Spermatogenesis”.

Spermatogenesis is a highly regulated cellular process within the seminiferous tubules that is structurally and functionally supported by Sertoli cells and peritubular myoid cells in the testes. This complex and synchronous cellular event consists of mitosis, meiosis, and a morphologic transformation of round haploid spermatids into polarized spermatozoa that carry genetic and epigenetic information to the next generation. Spermatogenesis has high energy demands and depends on both systematic and local hormones, signaling transduction molecules, adequate temperature, and bioenergetic metabolites shared via intercellular bridges of syncytial germ cells. Despite extensive studies carried out on understanding spermatogenesis at the cellular and molecular levels, advances in single-cell multi-omics have opened a new avenue for further deciphering the cellular and molecular mechanisms of spermatogenesis. With a growing body of testicular single-cell multi-omics data available, the molecular pathways discovered by bioinformatics analysis need to be validated and confirmed by experimental model systems in vitro and in vivo. Identification and confirmation of biomolecules regulating spermatogenesis are critically important not only for elucidating the cellular and molecular mechanisms of spermatogenesis but also for developing targeted approaches for male infertility treatment and male contraceptive development.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following:

  1. Mechanisms of hormonal, genetic, and temperature regulation of germ cell proliferation, differentiation, and death during spermatogenesis.
  2. Discover and elucidate the molecular pathways via single-cell multi-omics in testes.
  3. Validation and confirmation of the molecular pathways discovered via genomics, transcriptomics, proteomics, metabolomics, and lipidomics approaches in experimental model systems in vitro or in vivo by gene editing, transcriptional interference, and molecular or pharmacologic interventions.
  4. Deciphering the cellular and molecular mechanisms of testicular pathological conditions in animal and human testes.
  5. Protection, rescue, or suppression of spermatogenesis using biomolecules in experimental animal models.
  6. Mitochondrial dynamics and bioenergetic regulation of spermatogenesis.
  7. Sertoli cell, blood–testis barrier (BTB), and immunologic regulation of spermatogenesis.
  8. Application of biomolecules, biomaterials, and bioengineering for establishing in vitro spermatogenesis.

I look forward to receiving your contributions.

Dr. Yanhe Lue
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. Biomolecules is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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

  • spermatogenesis
  • regulation
  • biomolecules

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Published Papers (3 papers)

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Review

35 pages, 3356 KiB  
Review
Mechanisms of Hormonal, Genetic, and Temperature Regulation of Germ Cell Proliferation, Differentiation, and Death During Spermatogenesis
by María Maroto, Sara N. Torvisco, Cristina García-Merino, Raúl Fernández-González and Eva Pericuesta
Biomolecules 2025, 15(4), 500; https://doi.org/10.3390/biom15040500 - 29 Mar 2025
Viewed by 861
Abstract
Spermatogenesis is a complex and highly regulated process involving the proliferation, differentiation, and apoptosis of germ cells. This process is controlled by various hormonal, genetic, and environmental factors, including temperature. In hormonal regulation, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) are [...] Read more.
Spermatogenesis is a complex and highly regulated process involving the proliferation, differentiation, and apoptosis of germ cells. This process is controlled by various hormonal, genetic, and environmental factors, including temperature. In hormonal regulation, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) are essential for correct spermatogenesis development from the early stages and spermatogonia proliferation to germ cell maturation. Other hormones, like inhibin and activin, finely participate tuning the process of spermatogenesis. Genetic regulation involves various transcription factors, such as SOX9, SRY, and DMRT1, which are crucial for the development and maintenance of the testis and germ cells. MicroRNAs (miRNAs) play a significant role by regulating gene expression post-transcriptionally. Epigenetic modifications, including DNA methylation, histone modifications, and chromatin remodelling, are also vital. Temperature regulation is another critical aspect, with the testicular temperature maintained around 2–4 °C below body temperature, essential for efficient spermatogenesis. Heat shock proteins (HSPs) protect germ cells from heat-induced damage by acting as molecular chaperones, ensuring proper protein folding and preventing the aggregation of misfolded proteins during thermal stress. Elevated testicular temperature can impair spermatogenesis, increasing germ cell apoptosis and inducing oxidative stress, DNA damage, and the disruption of the blood–testis barrier, leading to germ cell death and impaired differentiation. The cellular mechanisms of germ cell proliferation, differentiation, and death include the mitotic divisions of spermatogonia to maintain the germ cell pool and produce spermatocytes. Spermatocytes undergo meiosis to produce haploid spermatids, which then differentiate into mature spermatozoa. Apoptosis, or programmed cell death, ensures the removal of defective germ cells and regulates the germ cell population. Hormonal imbalance, genetic defects, and environmental stress can trigger apoptosis during spermatogenesis. Understanding these mechanisms is crucial for addressing male infertility and developing therapeutic interventions. Advances in molecular biology and genetics continue to uncover the intricate details of how spermatogenesis is regulated at multiple levels, providing new insights and potential targets for treatment. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanism of Spermatogenesis)
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19 pages, 1371 KiB  
Review
Protective Role of Physical Activity and Antioxidant Systems During Spermatogenesis
by Cristina Antinozzi, Luigi Di Luigi, Laura Sireno, Daniela Caporossi, Ivan Dimauro and Paolo Sgrò
Biomolecules 2025, 15(4), 478; https://doi.org/10.3390/biom15040478 - 25 Mar 2025
Viewed by 548
Abstract
Oxidative stress is a significant factor that contributes to male infertility and sperm dysfunction. In this condition, an increase in ROS production exceeds the body’s antioxidant defenses, resulting in a decline in spermatozoa quality and fertilizing capacity. Furthermore, excessive ROS production has been [...] Read more.
Oxidative stress is a significant factor that contributes to male infertility and sperm dysfunction. In this condition, an increase in ROS production exceeds the body’s antioxidant defenses, resulting in a decline in spermatozoa quality and fertilizing capacity. Furthermore, excessive ROS production has been linked to the promotion of genomic damage, lipid peroxidation, inflammation, altered enzyme activity, and ultimately, irreversible alterations, cell death, and a decline in seminal parameters associated with male infertility. It is established that physical activity (PA), acting on inflammatory parameters and improving antioxidant defense, can alleviate the negative effects caused by free radicals, offering numerous health benefits and positively influencing sperm quality. The objective of this review is to highlight the mechanisms of ROS production, the physiological and pathophysiological roles of ROS in relation to the male reproductive system, and recent knowledge on the impact of some protocols of PA on these systems and the molecular mechanisms involved. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanism of Spermatogenesis)
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23 pages, 3625 KiB  
Review
Elucidating the Transcriptional States of Spermatogenesis—Joint Analysis of Germline and Supporting Cell, Mice and Human, Normal and Perturbed, Bulk and Single-Cell RNA-Seq
by Ali AbuMadighem, Ofir Cohen and Mahmoud Huleihel
Biomolecules 2024, 14(7), 840; https://doi.org/10.3390/biom14070840 - 12 Jul 2024
Viewed by 2476
Abstract
In studying the molecular underpinning of spermatogenesis, we expect to understand the fundamental biological processes better and potentially identify genes that may lead to novel diagnostic and therapeutic strategies toward precision medicine in male infertility. In this review, we emphasized our perspective that [...] Read more.
In studying the molecular underpinning of spermatogenesis, we expect to understand the fundamental biological processes better and potentially identify genes that may lead to novel diagnostic and therapeutic strategies toward precision medicine in male infertility. In this review, we emphasized our perspective that the path forward necessitates integrative studies that rely on complementary approaches and types of data. To comprehensively analyze spermatogenesis, this review proposes four axes of integration. First, spanning the analysis of spermatogenesis in the healthy state alongside pathologies. Second, the experimental analysis of model systems (in which we can deploy treatments and perturbations) alongside human data. Third, the phenotype is measured alongside its underlying molecular profiles using known markers augmented with unbiased profiles. Finally, the testicular cells are studied as ecosystems, analyzing the germ cells alongside the states observed in the supporting somatic cells. Recently, the study of spermatogenesis has been advancing using single-cell RNA sequencing, where scientists have uncovered the unique stages of germ cell development in mice, revealing new regulators of spermatogenesis and previously unknown cell subtypes in the testis. An in-depth analysis of meiotic and postmeiotic stages led to the discovery of marker genes for spermatogonia, Sertoli and Leydig cells and further elucidated all the other germline and somatic cells in the testis microenvironment in normal and pathogenic conditions. The outcome of an integrative analysis of spermatogenesis using advanced molecular profiling technologies such as scRNA-seq has already propelled our biological understanding, with additional studies expected to have clinical implications for the study of male fertility. By uncovering new genes and pathways involved in abnormal spermatogenesis, we may gain insights into subfertility or sterility. Full article
(This article belongs to the Special Issue Cellular and Molecular Mechanism of Spermatogenesis)
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