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Cells
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Advances in Spermatogenesis
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Advances in Spermatogenesis

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

Deadline for manuscript submissions: 20 June 2025 | Viewed by 5035

Special Issue Editors

Dr. Zhibing Zhang

E-Mail Website
Guest Editor
School of Medicine, Wayne State University, Detroit, MI, USA
Interests: manchette; intraflagellar transport; transcriptional regulation; acrosome biogenesis
Special Issues, Collections and Topics in MDPI journals
Dr. Changmin Niu

E-Mail Website
Guest Editor
School of Nursing—School of Public Health, Yangzhou University, Yangzhou, China
Interests: male infertility; spermatogenesis; oligoasthenospermia; spermiogenesis; fertilization

Special Issue Information

Dear Colleagues,

We are pleased to initiate a new Special Issue entitled “Advance in Spermatogenesis”.

Spermatogenesis is a complex process that occurs in the testes and enables sperm production. This process begins from puberty and involves stem-cell proliferation; meiotic division, which results in haploid gametes; and spermiogenesis, through which highly polarized sperm is formed. The whole process is precisely regulated; genetic and epigenetic regulation are two fundamental mechanisms, and these work alongside many other factors such as steroid hormones, which play an essential role in spermatogenesis. Extensive studies have been carried out in order to understand spermatogenesis at the cellular and molecular level and promote advances in techniques such as single-cell multi-omics and organoid culture, which have opened new avenues for further deciphering the mechanisms of spermatogenesis. Fully understanding the regulatory mechanisms of spermatogenesis will not only aid in the identification of the genetic factors of male infertility, but also provide novel approaches for the treatment of the disease. Finally, these novel findings will guide us in the development of male-based contraceptive drugs. The main aim of this Special Issue is to introduce novel findings regarding the regulation of spermatogenesis, particularly studies using state-of-the-art techniques.

In this Special Issue of Cells, we invite researchers to submit their original research articles, reviews, or communications related to the theme of "Advance in Spermatogenesis".

Dr. Zhibing Zhang
Dr. Changmin Niu
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. Cells is an international peer-reviewed open access semimonthly 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
  • mitosis
  • meiosis
  • spermiogenesis
  • omics
  • organoid culture
  • infertility
  • contraception

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Published Papers (4 papers)

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Research

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14 pages, 9436 KiB  
Article
Non-Redundant Essential Roles of Proteasomal Ubiquitin Receptors Rpn10 and Rpn13 in Germ Cell Formation and Fertility
by Wan-Yu Yue, Yi Zhang, Tian-Xia Jiang and Xiao-Bo Qiu
Cells 2025, 14(10), 696; https://doi.org/10.3390/cells14100696 - 12 May 2025
Viewed by 215
Abstract
Primordial germ cells (PGCs) undergo proliferation, migration, and sexual differentiation to produce gonocytes, which eventually generate germ cells. The proteasome, which degrades most cellular proteins, is a protein complex with dozens of subunits. The proteasomal ubiquitin receptors Rpn10 and Rpn13 have been shown [...] Read more.
Primordial germ cells (PGCs) undergo proliferation, migration, and sexual differentiation to produce gonocytes, which eventually generate germ cells. The proteasome, which degrades most cellular proteins, is a protein complex with dozens of subunits. The proteasomal ubiquitin receptors Rpn10 and Rpn13 have been shown to play partially overlapping roles in binding ubiquitin chains in vitro and in liver function in vivo. However, the specific role of Rpn10 and Rpn13 in germ cell production remains unclear. We show here that Rpn10 and Rpn13 are each essential for germ cell production and fertility. The conditional deletion of either Rpn10 or Rpn13 in PGCs results in infertility in both male and female mice. Germ cells in testes and ovaries all decreased dramatically in the Rpn13 conditional knockout (cKO) mice. Specifically, the deletion of Rpn13 in PGCs disrupts the assembly of the 26S proteasome, reduces the number of PGCs, and blocks the meiosis of spermatocytes at the zygotene stage during prophase I; on the other hand, the deletion of Rpn10 in PGCs sharply reduces PGC migration. These results are important for understanding the roles of Rpn10 and Rpn13 in germ cell development and related reproductive diseases. Full article
(This article belongs to the Special Issue Advances in Spermatogenesis)
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17 pages, 6700 KiB  
Article
The Role of Plzf in Spermatogonial Stem Cell Maintenance and Differentiation: Mapping the Transcriptional Dynamics and Key Interactions
by Nima Ghasemi, Hossein Azizi, Seyedeh-Kiana Razavi-Amoli and Thomas Skutella
Cells 2024, 13(23), 1930; https://doi.org/10.3390/cells13231930 - 21 Nov 2024
Cited by 1 | Viewed by 1361
Abstract
Spermatogonial stem cells (SSCs) sustain and modulate spermatogenesis through intricate signaling pathways and transcription factors. Promyelocytic leukemia zinc-finger (Plzf, also known as Zbtb16) has been identified as a critical transcription factor influencing various signaling and differentiation pathways. Plzf plays a [...] Read more.
Spermatogonial stem cells (SSCs) sustain and modulate spermatogenesis through intricate signaling pathways and transcription factors. Promyelocytic leukemia zinc-finger (Plzf, also known as Zbtb16) has been identified as a critical transcription factor influencing various signaling and differentiation pathways. Plzf plays a pivotal role in regulating the differentiation properties of SSCs and is essential for the proper maintenance of spermatogenesis. However, the transcription patterns of Plzf along the seminiferous tubules and its interaction network with adjacent partners still need to be fully elucidated. This study employed immunostaining techniques coupled with Fluidigm quantitative real-time polymerase chain reaction (Fluidigm qPCR) to quantify Plzf expression in undifferentiated and differentiated spermatogonia. Furthermore, we utilized bioinformatics analyses to identify Plzf partners and their associations with other regulatory factors. Immunohistostaining (IMH) revealed a high expression of Plzf in cells near the basal membrane of seminiferous tubules and a lower expression in the middle regions in vivo. Immunocytochemistry (ICC) demonstrated that undifferentiated spermatogonia exhibited significant Plzf positivity, whereas differentiated spermatogonia showed reduced Plzf expression in vitro. Fluidigm qPCR confirmed a significant differential expression of Plzf between undifferentiated and differentiated spermatogonia. In silico differential expression analysis between undifferentiated spermatogonia and spermatids indicated that Plzf is closely associated with Mycn, Lin28a, Kras, Ccnd1, and Jak1, highlighting the importance of these partnerships during spermatogenesis. Our findings suggest that the network of Plzf-related partners and their associated proteins involves differentiation, localization, apoptosis, and signal transduction. This comprehensive approach advances our understanding of Plzf transcription patterns and sheds light on its interactions with other cellular factors, revealing previously obscure pathways and interactions. These insights could lead to more effective diagnostic strategies for reproductive system-related diseases and inform the development of improved therapeutic and clinical applications. Full article
(This article belongs to the Special Issue Advances in Spermatogenesis)
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14 pages, 26431 KiB  
Article
Establishment and Characterization of Testis Organoids with Proliferation and Differentiation of Spermatogonial Stem Cells into Spermatocytes and Spermatids
by Dong Zhang, Wencong Jin, Yinghong Cui and Zuping He
Cells 2024, 13(19), 1642; https://doi.org/10.3390/cells13191642 - 2 Oct 2024
Cited by 2 | Viewed by 2201
Abstract
Organoids play pivotal roles in uncovering the molecular mechanisms underlying organogenesis, intercellular communication, and high-throughput drug screening. Testicular organoids are essential for exploring the genetic and epigenetic regulation of spermatogenesis in vivo and the treatment of male infertility. However, the formation of testicular [...] Read more.
Organoids play pivotal roles in uncovering the molecular mechanisms underlying organogenesis, intercellular communication, and high-throughput drug screening. Testicular organoids are essential for exploring the genetic and epigenetic regulation of spermatogenesis in vivo and the treatment of male infertility. However, the formation of testicular organoids with full spermatogenesis has not yet been achieved. In this study, neonatal mouse testicular cells were isolated by two-step enzymatic digestion, and they were combined with Matrigel and transplanted subcutaneously into nude mice. Histological examination (H&E) staining and immunohistochemistry revealed that cell grafts assembled to form seminiferous tubules that contained spermatogonial stem cells (SSCs) and Sertoli cells, as illustrated by the co-expression of PLZF (a hallmark for SSCs) and SOX9 (a marker for Sertoli cells) as well as the co-expression of UCHL1 (a hallmark for SSCs) and SOX9, after 8 weeks of transplantation. At 10 weeks of transplantation, SSCs could proliferate and differentiate into spermatocytes as evidenced by the expression of PCNA, Ki67, c-Kit, SYCP3, γ-HA2X, and MLH1. Notably, testicular organoids were seen, and spermatids were observed within the lumen of testicular organoids after 16 weeks of transplantation, as shown by the presence of TNP1 and ACROSIN (hallmarks for spermatids). Collectively, these results implicate that we successfully established testicular organoids with spermatogenesis in vivo. This study thus provides an excellent platform for unveiling the mechanisms underlying mammalian spermatogenesis, and it might offer valuable male gametes for treating male infertility. Full article
(This article belongs to the Special Issue Advances in Spermatogenesis)
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Review

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17 pages, 5006 KiB  
Review
The Terminal Segment of the Seminiferous Tubule: The Current Discovery of Its Morphofunctional Importance in Mammals
by Vicente Seco-Rovira, Ester Beltrán-Frutos, Jesús Martínez-Hernández, Juan Francisco Madrid and Luis Miguel Pastor
Cells 2025, 14(4), 305; https://doi.org/10.3390/cells14040305 - 18 Feb 2025
Viewed by 719
Abstract
The morphophysiology of intratesticular sperm pathways in mammals, including humans, is poorly understood. The seminiferous tubule is continuous with the straight tubule; however, its final portion—the terminal segment (TS)—has a different tissue composition. This paper reviews the most important histological results from mammal [...] Read more.
The morphophysiology of intratesticular sperm pathways in mammals, including humans, is poorly understood. The seminiferous tubule is continuous with the straight tubule; however, its final portion—the terminal segment (TS)—has a different tissue composition. This paper reviews the most important histological results from mammal studies from the last decades of the 20th century, including the different nomenclatures given to the TS. The TS presents a loss of spermatogenesis and is lined mainly with modified Sertoli cells. There is no unanimity among authors when it comes to naming and defining TS. In the last ten years, studies on rats and mice have highlighted the importance of this testicular zone, proposing that there is a high proliferation of modified Sertoli cells with an undifferentiated cellular profile associated with stem spermatogonia. In hamsters, an immunohistochemical study showed the existence of heterogeneity between these cells, and the surrounding interstitium presents numerous Leydig cells that are ultrastructurally different from those of the rest of the testis rest. In conclusion, we have only just begun to understand the tissue biology of TS. Emerging research is very promising; it can potentially modify our current knowledge of testicular biology and be very useful in promoting the advancement of male fertility restoration therapies in andrology. Full article
(This article belongs to the Special Issue Advances in Spermatogenesis)
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