Wu JH, Lin F, Wang YH, Xie JP, Guo SL, Liu PY. FOXP1 promotes the proliferation and self-renewal of spermatogonial stem cells via the nuclear factor kappa B pathway. World J Stem Cells 2026; 18(5): 115482 [DOI: 10.4252/wjsc.v18.i5.115482]
Corresponding Author of This Article
Pei-Yan Liu, Department of Andrology, Ganzhou People’s Hospital of Jiangxi Province, No. 17 Hongqi Avenue, Ganzhou 341000, Jiangxi Province, China. lpygzsnxyxk@163.com
Research Domain of This Article
Urology & Nephrology
Article-Type of This Article
Basic Study
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Wu JH, Lin F, Wang YH, Xie JP, Guo SL, Liu PY. FOXP1 promotes the proliferation and self-renewal of spermatogonial stem cells via the nuclear factor kappa B pathway. World J Stem Cells 2026; 18(5): 115482 [DOI: 10.4252/wjsc.v18.i5.115482]
Jin-Hua Wu, Feng Lin, Yan-Hua Wang, Jiang-Ping Xie, Shu-Lin Guo, Pei-Yan Liu, Department of Andrology, Ganzhou People’s Hospital of Jiangxi Province, Ganzhou 341000, Jiangxi Province, China
Author contributions: Wu JH and Liu PY designed the study, supervised the laboratory experiments, conducted the experiments and drafted the manuscript; Lin F, Wang YH, Xie JP, and Guo SL assisted with the experiments and sample collection. All authors read and approved the final manuscript.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of Ganzhou People’s Hospital of Jiangxi Province (approval No. PJB2025-279-01).
Institutional animal care and use committee statement: The protocol for the animal experiment was reviewed and approved by the Ethics Committee of Fujian Anburui Biotechnology Co., Ltd., for experimental animal welfare (No. IACUC FJABR2024032101).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.
Corresponding author: Pei-Yan Liu, Department of Andrology, Ganzhou People’s Hospital of Jiangxi Province, No. 17 Hongqi Avenue, Ganzhou 341000, Jiangxi Province, China. lpygzsnxyxk@163.com
Received: November 7, 2025 Revised: December 25, 2025 Accepted: February 25, 2026 Published online: May 26, 2026 Processing time: 198 Days and 23 Hours
Abstract
BACKGROUND
The proliferation and self-renewal of spermatogonial stem cells (SSCs) are essential for maintaining the sperm production process. The molecular mechanisms of self-renewal and differentiation of SSCs have not been fully clarified, although the functions of some regulatory factors in SSCs have been previously reported.
AIM
To investigate the role of forkhead box P1 (FOXP1) in regulating the proliferation and self-renewal of SSCs and its potential mechanism via the nuclear factor kappa B (NF-κB) pathway.
METHODS
Testicular tissue was collected from 31 patients, including 18 obstructive azoospermia (OA) and 13 nonobstructive azoospermia cases. Hematoxylin and eosin staining was performed to analyze the morphological difference in human testicular tissue between the OA and nonobstructive azoospermia groups. Immunohistochemistry staining was used to evaluate the expression of FOXP1 in human testicle tissues. FOXP1 knockdown lentivirus was injected into mice testes, and immunohistochemistry staining and immunofluorescence assays of ETS variant gene 5 and promyelocytic leukemia zinc finger were performed to investigate the effect of FOXP1 on spermatogonia in mice. A Cell Counting Kit-8 assay was used to assess the proliferation of SSCs. SC75741 was used to inhibit the NF-κB pathway, and proliferating cell nuclear antigen, ETS variant gene 5, promyelocytic leukemia zinc finger, and phosphorylated-NF-κB p65 were detected via western blot analysis.
RESULTS
FOXP1 was highly expressed in the testicular tissue of patients with OA. FOXP1 knockdown inhibited the proliferation and self-renewal of SSCs in mice and in vitro. Consistently, FOXP1 overexpression promoted the SSCs’ proliferation and self-renewal, which was regulated through the NF-κB pathway.
CONCLUSION
FOXP1 may promote the proliferation and self-renewal of SSCs via the NF-κB pathway. This research offers a theoretical foundation for male infertility treatment.
Core Tip: Spermatogonial stem cells (SSCs) are the basis of spermatogenesis in mammals and can self-renew or differentiate into the various cell types in the germ cell lineage. SSC homeostasis dysregulation is closely associated with male infertility. This study revealed the role of forkhead box P1 in regulating the function of SSCs via the nuclear factor kappa B pathway, thus offering a basis for the diagnosis and treatment of male infertility.
