Abstract
BackgroundThis study tested the hypothesis that combined melatonin (Mel) and adipose-derived mesenchymal stem cells (ADMSCs) treatment was superior to either one alone on protecting the testis against acute testicular torsion-induced ischemia-reperfusion (TTIR) injury.Methods and resultsMale adult SD rats (n = 30) were equally categorized into group 1 (sham-operated control), group 2 [TTIR/by torsion of right/left testis (i.e., ischemia) with rotated 720° counterclockwise for 2 h, then detorsion (i.e., reperfusion) to the original position for 72 h], group 3 (TTIR + Mel/intraperitoneal administration/50 mg/kg at 30 min after ischemia, followed by 20 mg at 3 h and days 1/2/3 after TTIR), group 4 (TTIR + ADMSCs/1.2 × 106 cells/by tail-vein administration at 30 min after ischemia, followed by days 1/2 TTIR), and group 5 (TTIR + Mel + ADMSCs/tail-vein administration). The result showed that the protein expressions of oxidative-stress (NOX-1/NOX-2/oxidized-protein), apoptotic/mitochondrial-damaged (mitochondrial-Bax/cleaved-caspase3/cleaved-PARP/cytosolic-cytochrome C), and fibrotic (TGF-ß/Smad3) biomarkers as well as testicular damage scores were lowest in group 1, highest in group 2, and significantly higher in groups 3/4 than in group 5, but they showed no difference between groups 3/4, whereas the protein expressions of androgen receptor (AR) and vimentin showed an opposite pattern of oxidative stress (all p < 0.0001). The cellular levels of inflammation (MMP-9/MPO/CD68) exhibited an identical pattern, whereas the numbers of Sertoli cells, α-tubulin, AR and vimentin as well as thickness of seminiferous tubule exhibited an opposite pattern of oxidative stress among the groups (all p < 0.0001).ConclusionMel-ADMSCs effectively protected the testis against TTIR injury.
Highlights
Testicular torsion due to twisting of the spermatic cord is a serious urological emergency that is most commonly encountered in those of newborns, children, and adolescent males [1, 2]
Mel-adipose-derived mesenchymal stem cells (ADMSCs) effectively protected the testis against testicular torsion-induced ischemia-reperfusion (TTIR) injury
The result showed that the protein expressions of mitochondrial Bax, cleaved caspase 3, and cleaved Poly polymerase (PARP), three indices of apoptosis, were lowest in group 1 (i.e., sham-operated control (SC)), highest in group 2 (TTIR only), and significantly lower in group 5 (TTIR + Mel + ADMSCs) than in groups 3
Summary
Testicular torsion due to twisting of the spermatic cord is a serious urological emergency that is most commonly encountered in those of newborns, children, and adolescent males [1, 2]. It is well known that testicular ischemia-reperfusion (IR) injury represents the essential pathophysiology of testicular torsion, with ischemia caused by twisting of the spermatic cord, and reperfusion on its subsequent release. To quickly release the torsion (i.e., detorsion) by surgical intervention [1,2,3,4,5,6,7] This procedure which is a standard method for treatment of testicular torsion usually poses no difficulty for an interventional urologist. This study tested the hypothesis that combined melatonin (Mel) and adipose-derived mesenchymal stem cells (ADMSCs) treatment was superior to either one alone on protecting the testis against acute testicular torsion-induced ischemia-reperfusion (TTIR) injury
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