The Regulatory Effects of JAK2/STAT3 on Spermatogenesis and the Redox Keap1/Nrf2 Axis in an Animal Model of Testicular Ischemia Reperfusion Injury

Abstract

The male reproductive system requires the pleiotropic activity of JAK/STAT to maintain its function, especially spermatogenesis. The study aims to investigate the effect of JAK2 signaling on the expression of the Keap1/Nrf2 axis, spermatogenesis, and the Sertoli cells (Sc) junctions in an animal model of testicular ischemia reperfusion injury (tIRI). Testes subjected to tIRI exhibited increased JAK2/STAT3 activity associated with spermatogenic arrest and reduced expression of the Sc junctions. In addition, there was an increased protein expression of Keap1 and decreased Nrf2., which was coupled with the downregulation of gene expression of antioxidant enzymes. Reduced SOD and CAT activities were accompanied by increased lipid peroxidation and protein carbonylation during tIRI. Increased caspase 9 activity and Bax/Bcl2 ratio indicated initiation of apoptosis. Inhibition of JAK2 activity by AG490 maintained the integrity of spermatogenesis and SC junctions, normalized the expression of the Keap1/Nrf2 axis and its downstream antioxidant enzymes, and prevented germ cell apoptosis. The results further emphasized the regulatory role of JAK2/STAT3 on spermatogenesis, Keap1/Nrf2 signaling, and maintenance of the testicular redox balance to combat testicular dysfunction and male infertility.

Integrative analysis of transcriptomics and metabolomics reveals the protective effect and mechanism of salidroside on testicular ischemia-reperfusion injury

“…The damage caused by testicular torsion detorsion is called an ischemia-reperfusion (I/R) injury ( Chen et al, 2023 ), and I/R injuries occur after incidents of acute ischemia. Upon blood flow restoration, the testes appear to be injured by I/R, which is the primary pathophysiology of testicular torsion detorsion ( Wei and Huang, 2022 ; Almarzouq and Al, 2023 ; Alnajem and Al, 2023 ). In the I/R process, there is formation of excess reactive oxygen species (ROS), such as superoxide anions, nitric oxide, hydrogen peroxide, and hydroxyl radicals, in the affected tissue; these ROS are highly reactive and can damage the cellular constituents, such as lipids, proteins, DNA, and carbohydrates.…”