GSK1016790A, a TRPV4 Agonist, Repairs Spermatogenic Dysfunction Caused By Diabetes.

Abstract

As a devastating metabolic disease, diabetic testicular damage can lead to impaired spermatogenesis and sexual dysfunction. Transient receptor potential cation channel subfamily vanilloid 4 (TRPV4) plays complex roles in the pathogenesis of diabetes and its complications and plays a major role in the development of apoptosis and related mechanisms. This study aimed to investigate the effects of the TRPV4 agonist GSK1016790A on sperm parameters, spermatogenic cell apoptosis and testicular histopathology in STZ-induced diabetic mice. A model of diabetes was induced in 8-week-old male ICR mice by an intraperitoneal injection of STZ for five consecutive days. At week 7, the mice were intraperitoneally injected with the TRPV4 agonist GSK1016790A or normal saline (NS) for 7 days. At week 8, the animals were sacrificed. The results revealed that the expression of TRPV4 in the testes of STZ-induced diabetic mice decreased, and the testes exhibited the destruction of tissue structure, decreases in the total sperm count and viability, an increase in the sperm deformity rate, and an increase in apoptosis. These symptoms were reversed by increased TRPV4 expression following the injection of the TRPV4 agonist GSK1016790A. Increased TRPV4 expression can ameliorate cell apoptosis in the STZ-induced testes of diabetic mice and alleviate spermatogenic dysfunction in the testes.