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

Reproductive Biology and Endocrinology

Research

David Yiu Leung Chan¹  Wenzhong Zhao²  Xinan Li³  Weiqiang Xiao⁴  Yongtong Zhu⁴  Shanchao Zhao⁴  Daxiong Huang⁴  Fengbo Cai⁴  Qiang Ma⁴  Qingjun Chu⁴  Yisheng Yang⁴  Wantao Liu⁴ 

[1] Assisted Reproductive Technology Unit, Department of Obstetrics and Gynaecology, Faculty of Medicine, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China;NHC Key Laboratory of Male Reproduction and Genetics, Family Planning Research Institute of Guangdong Province, Guangzhou, China;School of Basic Medical Sciences, Guangzhou Medical University, 511436, Guangzhou, People’s Republic of China;The First School of Clinical Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China;

关键词: Sertoli cell-only syndrome (SCOS);    CASP1;    CASP4;    Pyroptosis;   

DOI  :  10.1186/s12958-023-01101-w

 received in 2023-01-19, accepted in 2023-05-11,  发布年份 2023

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© The Author(s) 2023

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