ArticleReproductive biology and endocrinology : RB&E2023
Testis cell pyroptosis mediated by CASP1 and CASP4: possible sertoli cell-only syndrome pathogenesis.
Article in Reproductive biology and endocrinology : RB&E, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 9 citations in OpenAlex.
- Sertoli cell oxidative stress as a convergent hazard endpoint for environmental toxicants: A systematic review, meta-analysis, and AOP-based assessment.Redox biology · 2026Review
- A multi-mics exploration of programmed cell death in non-obstructive azoospermia: identifying TLR4 as a central regulator and therapeutic target.Frontiers in cell and developmental biology · 2026Article
- Using Blood-Based Biomarkers to Facilitate the Diagnosis of Alzheimer's Disease: Insights from a Novel Pyroptosis-Associated Molecular Signature Model.Molecular neurobiology · 2025Article
- CCR5 + T cells as a potential biomarker for primary Sjögren's disease based on bioinformatics analysis.Clinical rheumatology · 2025Article
- Interplay of Ferroptosis, Cuproptosis, Autophagy and Pyroptosis in Male Infertility: Molecular Crossroads and Therapeutic Opportunities.International journal of molecular sciences · 2025Review
- Sertoli cells-only syndrome: current clinical approaches and ongoing research trends.Frontiers in endocrinology · 2025Review
- MALDI Imaging Mass Spectrometry Reveals Lipid Alterations in Physiological and Sertoli Cell-Only Syndrome Human Testicular Tissue Sections.International journal of molecular sciences · 2024Article
- Oxidative Stress Biomarkers in Male Infertility: Established Methodologies and Future Perspectives.Genes · 2024Review
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSertoli cell-only syndrome (SCOS) is the most serious pathological type of non-obstructive azoospermia. Recently, several genes related to SCOS have been identified, including FANCM, TEX14, NR5A1, NANOS2, PLK4, WNK3, and FANCA, but they cannot fully explain the pathogenesis of SCOS. This study attempted to explain spermatogenesis dysfunction in SCOS through testicular tissue RNA sequencing and to provide new targets for SCOS diagnosis and therapy.
methodsWe analyzed differentially expressed genes (DEGs) based on RNA sequencing of nine patients with SCOS and three patients with obstructive azoospermia and normal spermatogenesis. We further explored the identified genes using ELISA and immunohistochemistry.
resultsIn total, 9406 DEGs were expressed (Log2|FC|≥ 1; adjusted P value < 0.05) in SCOS samples, and 21 hub genes were identified. Three upregulated core genes were found, including CASP4, CASP1, and PLA2G4A. Thus, we hypothesized that testis cell pyroptosis mediated by CASP1 and CASP4 might be involved in SCOS occurrence and development. ELISA verified that CASP1 and CASP4 activities in the testes of patients with SCOS were significantly higher than those in patients with normal spermatogenesis. Immunohistochemical results showed that CASP1 and CASP4 in the normal spermatogenesis group were mainly expressed in the nuclei of spermatogenic, Sertoli, and interstitial cells. CASP1 and CASP4 in the SCOS group were mainly expressed in the nuclei of Sertoli and interstitial cells because of the loss of spermatogonia and spermatocytes. CASP1 and CASP4 expression levels in the testes of patients with SCOS were significantly higher than those in patients with normal spermatogenisis. Furthermore, the pyroptosis-related proteins GSDMD and GSDME in the testes of patients with SCOS were also significantly higher than those in control patients. ELISA also showed that inflammatory factors (IL-1 β, IL-18, LDH, and ROS) were significantly increased in the SCOS group.
conclusionsFor the first time, we found that cell pyroptosis-related genes and key markers were significantly increased in the testes of patients with SCOS. We also observed many inflammatory and oxidative stress reactions in SCOS. Thus, we propose that testis cell pyroptosis mediated by CASP1 and CASP4 could participate in SCOS occurrence and development.
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