Background: This study tested the hypothesis that combined melatonin (Mel) and adipose-derived mesenchymal stem cell (ADMSC) treatment was superior to either one alone on protecting the testis against acute testicular torsion-induced ischemia-reperfusion (TTIR) injury.
Methods and Results: Male-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 degrees counterclockwisely for 2h, then detorsion (i.e., reperfusion) to the original position for 72h], group 3 (TTIR + Mel/intraperitoneal administration/50 mg/kg at 30 minutes after ischemia, followed by 20 mg at 3h and days 1/2/3 after TTIR), group 4 (TTIR + ADMSC/1.2 x 106 cells/intravenous administration at 30 minutes after ischemia, followed by days 1/2 TTIR) and group 5 (TTIR + Mel + ADMSC). 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).
Conclusion: Mel-ADMSCs effectively protected the testis against TTIR injury.

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Posted 12 Mar, 2021
On 01 May, 2021
Received 30 Apr, 2021
On 28 Apr, 2021
Received 22 Mar, 2021
Received 13 Mar, 2021
On 13 Mar, 2021
On 05 Mar, 2021
Invitations sent on 05 Mar, 2021
On 05 Mar, 2021
On 05 Mar, 2021
On 03 Mar, 2021
Posted 12 Mar, 2021
On 01 May, 2021
Received 30 Apr, 2021
On 28 Apr, 2021
Received 22 Mar, 2021
Received 13 Mar, 2021
On 13 Mar, 2021
On 05 Mar, 2021
Invitations sent on 05 Mar, 2021
On 05 Mar, 2021
On 05 Mar, 2021
On 03 Mar, 2021
Background: This study tested the hypothesis that combined melatonin (Mel) and adipose-derived mesenchymal stem cell (ADMSC) treatment was superior to either one alone on protecting the testis against acute testicular torsion-induced ischemia-reperfusion (TTIR) injury.
Methods and Results: Male-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 degrees counterclockwisely for 2h, then detorsion (i.e., reperfusion) to the original position for 72h], group 3 (TTIR + Mel/intraperitoneal administration/50 mg/kg at 30 minutes after ischemia, followed by 20 mg at 3h and days 1/2/3 after TTIR), group 4 (TTIR + ADMSC/1.2 x 106 cells/intravenous administration at 30 minutes after ischemia, followed by days 1/2 TTIR) and group 5 (TTIR + Mel + ADMSC). 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).
Conclusion: Mel-ADMSCs effectively protected the testis against TTIR injury.

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7
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