Academic Journal
GLUL deficiency causes sperm acrosome defects and male infertility via influencing redox balance in mice.
| Title: | GLUL deficiency causes sperm acrosome defects and male infertility via influencing redox balance in mice. |
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| Authors: | Lin M; Center of Reproductive Medicine, Affiliated Women's Hospital of Jiangnan University, Wuxi Jiangsu, 214002, China; Wuxi School of Medicine, Jiangnan University, Wuxi, China., Feng Y; Center of Reproductive Medicine, Affiliated Women's Hospital of Jiangnan University, Wuxi Jiangsu, 214002, China; Wuxi School of Medicine, Jiangnan University, Wuxi, China., Zhang Y; Center of Reproductive Medicine, Affiliated Women's Hospital of Jiangnan University, Wuxi Jiangsu, 214002, China., Wang H; Center of Reproductive Medicine, Affiliated Women's Hospital of Jiangnan University, Wuxi Jiangsu, 214002, China., Wang Y; Center of Reproductive Medicine, Affiliated Women's Hospital of Jiangnan University, Wuxi Jiangsu, 214002, China., Feng N; Wuxi School of Medicine, Jiangnan University, Wuxi, China; Department of Urology, Jiangnan University Medical Center, Wuxi Jiangsu, 214002, China. Electronic address: hqw1401@163.com., He Q; Department of Public Health, Affiliated Women's Hospital of Jiangnan University, Wuxi Jiangsu, 214002, China. Electronic address: n.feng@jiangnan.edu.cn. |
| Source: | Free radical biology & medicine [Free Radic Biol Med] 2026 Aug 01; Vol. 251, pp. 322-332. Date of Electronic Publication: 2026 Apr 21. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Elsevier Science Country of Publication: United States NLM ID: 8709159 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4596 (Electronic) Linking ISSN: 08915849 NLM ISO Abbreviation: Free Radic Biol Med Subsets: MEDLINE |
| Imprint Name(s): | Publication: Tarrytown, NY : Elsevier Science Original Publication: New York : Pergamon, c1987- |
| MeSH Terms: | Infertility, Male*/genetics , Infertility, Male*/pathology , Infertility, Male*/metabolism , Acrosome*/pathology , Acrosome*/metabolism , Spermatozoa*/metabolism , Spermatozoa*/pathology, Spermatogenesis/genetics ; Glutathione/administration & dosage ; Epididymis/metabolism ; Animals ; Male ; Mice ; Oxidation-Reduction ; Mice, Knockout ; Oxidative Stress ; Sperm Injections, Intracytoplasmic |
| Abstract: | Glutamate-ammonia ligase (GLUL) catalyzes the syntheses of glutamine, as the antioxidant that has been shown to influence sperm quality in mammals. Research on the precise functions of the GLUL gene during spermatogenesis has been constrained by the structural complexity of the testis. In this study, we established a mouse model with postnatal, germ cell-specific deletion of GLUL. Conditional knockout (cKO) of GLUL led to reduced male fertility. Epididymal sperm from cKO mice exhibited acrosomal malformation, diminished acrosin activity, and redox imbalance. Moreover, GLUL deficiency was found to alter protein levels of Spam1 and Tssk3 in epididymal sperm. These functional deficits could be partially rescued by intraperitoneal glutathione (GSH) administration or by intracytoplasmic sperm injection (ICSI). Collectively, our results demonstrate that GLUL in germ cells is essential for combating oxidative stress during spermatogenesis in mice. These findings enhance the understanding of GLUL's role in male germ cell development and propose GSH supplementation as a potential therapeutic strategy for conditions associated with low acrosin activity. (Copyright © 2026 Elsevier Inc. All rights reserved.) |
| Competing Interests: | Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. |
| Contributed Indexing: | Keywords: GLUL; GSH; ICSI; Redox imbalance; Reduced male fertility |
| Substance Nomenclature: | GAN16C9B8O (Glutathione) |
| Entry Date(s): | Date Created: 20260423 Date Completed: 20260715 Latest Revision: 20260715 |
| Update Code: | 20260716 |
| DOI: | 10.1016/j.freeradbiomed.2026.04.030 |
| PMID: | 42025703 |
| Database: | MEDLINE |
| ISSN: | 1873-4596 |
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| DOI: | 10.1016/j.freeradbiomed.2026.04.030 |