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.

Abstract

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.

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