Related Experiment Video
Updated: Jul 27, 2025

Isolation of Sertoli Cells and Peritubular Cells from Rat Testes
Published on: February 8, 2016
Testis cell pyroptosis mediated by CASP1 and CASP4: possible sertoli cell-only syndrome pathogenesis
Wantao Liu1, Xinan Li2, Qiang Ma1
1The First School of Clinical Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Background:
Sertoli 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.
Methods:
We 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.
Results:
In 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.
Conclusions:
For 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.
Insights
Sertoli cell-only syndrome (SCOS) involves increased cell pyroptosis, indicated by elevated CASP1 and CASP4 gene activity. This study links pyroptosis and inflammation to SCOS pathogenesis, offering new diagnostic and therapeutic targets.
Area of Science:
- Reproductive Biology
- Molecular Genetics
- Cellular Pathology
Background:
- Sertoli cell-only syndrome (SCOS) is a severe form of non-obstructive azoospermia.
- Existing genetic discoveries do not fully explain SCOS pathogenesis.
- This study investigates spermatogenesis dysfunction in SCOS using RNA sequencing.
Purpose of the Study:
- To identify novel molecular targets for SCOS diagnosis and therapy.
- To elucidate the role of testicular gene expression in SCOS.
- To explore the potential involvement of pyroptosis in SCOS development.
Main Methods:
- RNA sequencing analysis of testicular tissue from SCOS patients and controls.
- Identification and analysis of differentially expressed genes (DEGs).
- Validation of key genes and proteins using ELISA and immunohistochemistry.
Main Results:
- 9406 DEGs identified in SCOS samples, with 21 hub genes found.
- Significantly upregulated CASP1, CASP4, and PLA2G4A genes in SCOS testes.
- Elevated CASP1, CASP4, GSDMD, GSDME, IL-1β, IL-18, LDH, and ROS in SCOS patients, indicating pyroptosis and inflammation.
Conclusions:
- Cell pyroptosis-related genes and markers are significantly increased in SCOS testes.
- CASP1 and CASP4-mediated pyroptosis may play a role in SCOS occurrence and development.
- Inflammatory and oxidative stress reactions are prominent in SCOS.
Related Concept Videos
Caspases
Spermatogenesis
Overview of Cell Death
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
The Extrinsic Apoptotic Pathway
Testes: Histology
The spermatogenic cells, responsible for producing sperm, are...
The Intrinsic Apoptotic Pathway

