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Open Access 01-12-2023 | Mumps Orchitis | Research

Testis cell pyroptosis mediated by CASP1 and CASP4: possible sertoli cell-only syndrome pathogenesis

Authors: Wantao Liu, Xinan Li, Qiang Ma, Yongtong Zhu, Wenzhong Zhao, Yisheng Yang, Weiqiang Xiao, Daxiong Huang, Fengbo Cai, David Yiu Leung Chan, Shanchao Zhao, Qingjun Chu

Published in: Reproductive Biology and Endocrinology | Issue 1/2023

Abstract

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.

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Title: Testis cell pyroptosis mediated by CASP1 and CASP4: possible sertoli cell-only syndrome pathogenesis
Authors: Wantao Liu
Xinan Li
Qiang Ma
Yongtong Zhu
Wenzhong Zhao
Yisheng Yang
Weiqiang Xiao
Daxiong Huang
Fengbo Cai
David Yiu Leung Chan
Shanchao Zhao
Qingjun Chu
Publication date: 01-12-2023
Publisher: BioMed Central
Keyword: Mumps Orchitis
Published in: Reproductive Biology and Endocrinology / Issue 1/2023
Electronic ISSN: 1477-7827
DOI: https://doi.org/10.1186/s12958-023-01101-w

2024 ESC Congress

Springer Medicine

Testis cell pyroptosis mediated by CASP1 and CASP4: possible sertoli cell-only syndrome pathogenesis

Abstract

Background

Methods

Results

Conclusions

2024 ESC Congress

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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