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Spermatogonial stem cells (SSCs) are essential for the initiation and continuation of spermatogenesis, a process fundamental to male fertility. Despite extensive studies on mouse SSCs, the mechanisms governing self-renewal and differentiation in human SSCs remain to be elucidated. This study investigated the regulatory mechanisms of SSCs by analyzing single-cell sequencing data from the GEO dataset of human testis. Analysis revealed dominant expression of CITED2 in human SSCs. Reduction of CITED2 levels in hSSC lines significantly inhibited proliferation and increased apoptosis. Protein interaction prediction and immunoprecipitation identified interactions between CITED2 and EP300 in SSC lines. RNA sequencing results indicated that CITED2 knockdown significantly affected the MAPK pathway and the HSPA6 gene. Overexpression of HSPA6 mitigated the proliferative and apoptotic changes provoked by CITED2 downregulation. These findings provide novel insights into the regulatory and functional mechanisms of CITED2-mediated hSSC development.
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http://dx.doi.org/10.1155/sci/2362489 | DOI Listing |
Stem Cell Res Ther
September 2025
Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
Background: Platelet-rich plasma (PRP) and its subtype, plasma rich in growth factors (PRGF), are autologous blood-derived products that have garnered increasing attention as personalized therapeutic tools in the field of male fertility. This systematic review aims to evaluate the current in vitro and in vivo evidence regarding the potential applications of platelet-derived products in various domains of male reproductive health, including in vitro spermatogenesis, sperm preservation, treatment of male infertility, mitigation of testicular toxicity, and management of testicular torsion/detorsion (T/D) injury.
Strategy: This review was conducted in accordance with PRISMA guidelines and was prospectively registered in PROSPERO.
Reprod Sci
September 2025
Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, Bibinagar, Hyderabad, Telangana, 508126, India.
Male infertility remains a significant global reproductive health challenge, frequently attributed to genetic mutations impairing spermatogenesis and sperm function. This narrative review aims to explore the genetic and molecular underpinnings of male infertility and evaluate the emerging role of Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR-associated protein 9 (CRISPR/Cas9) genome editing as a diagnostic and therapeutic tool, while addressing its associated ethical, technical, and safety considerations. A Comprehensive literature search was conducted across PubMed, Scopus, Web of Science databases, covering studies published between September 1992 and April 2025.
View Article and Find Full Text PDFCell Mol Life Sci
September 2025
Department of Orthopedics, The Seventh Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Shenzhen, 410000, Shenzhen, China.
Non-obstructive azoospermia (NOA) is a leading cause of male infertility, characterized by impaired spermatogenesis. Recent studies suggest that ferroptosis, an iron-dependent form of cell death, may contribute to testicular dysfunction, however, its role in NOA remains underexplored. In this study, we investigated the roles of NUPR1 and MYC in regulating ferroptosis in human spermatogonial stem cells (SSCs) and evaluated their potential as therapeutic targets for NOA.
View Article and Find Full Text PDFEcotoxicol Environ Saf
August 2025
Department of Reproductive Medicine, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China. Electronic address:
Although dietary factors are increasingly implicated as crucial determinants of male fertility, specific dietary risk factors and their metabolic mechanisms remain poorly understood. In this study, patients with non-obstructive azoospermia (NOA) or severe oligospermia (EO) demonstrated significantly elevated erucic acid (EA) levels, with a nearly 3-fold increase in serum (P < 0.0001) and a 27 % increase in semen (P = 0.
View Article and Find Full Text PDFAntioxidants (Basel)
July 2025
Institute for Anatomy and Cell Biology, Medical Faculty, University of Heidelberg, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany.
Background: Oxidative stress is a critical factor contributing to male infertility, impairing spermatogonial stem cells (SSCs) and disrupting normal spermatogenesis. This study aimed to isolate and characterize human SSCs and to investigate oxidative stress-related gene expression, protein interaction networks, and developmental trajectories involved in SSC function.
Methods: SSCs were enriched from human orchiectomy samples using CD49f-based magnetic-activated cell sorting (MACS) and laminin-binding matrix selection.