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Huang IS et al., 2023: The impact of low intensity extracorporeal shock waves on testicular spermatogenesis demonstrated in a rat model

Huang IS, Chen WJ, Wang ZL, Li LH, Chen YK, Wu YL, Brannigan RE, Juan CC, Huang WJ.
Department of Urology, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
Department of Physiology, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.
Department of Urology, College of Medicine, and Shu-Tien Urological Science Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan, ROC.
Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan, ROC.
Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Abstract

Background: In rodent models, low-intensity extracorporeal shock wave therapy has been shown to negatively impact semen concentration after treatment on the penis, implying that the reproductive system in close proximity may be indirectly affected by this modality. We hypothesized that shock waves are detrimental to spermatogenesis, and the aim of this study was to evaluate the effect of shock waves on spermatogenesis after direct shockwave treatment on testes using different energy settings.

Methods: Twenty-five male Sprague Dawley rats, 8 weeks old, were divided into five groups, including one control group and four treatment groups each treated using shock waves of different intensities. All rats in the treatment groups received 2000 shocks on the left testis twice a week for 4 weeks, with shock wave intensity and frequency varied by treatment group: 0.1 mJ/mm 2 at 4 Hz for Group A, 0.15 mJ/mm 2 at 4 Hz for Group B, 0.35 mJ/mm 2 at 4 Hz for Group C, and 0.55mJ/mm 2 at 3 Hz for Group D. At the end of the experiment, sperm collected from the epididymis was evaluated for concentration and motility. Testicular spermatogenesis, the apoptotic index of germ cells, and the expression of a meiotic-specific gene were also analyzed.

Results: The treatment group receiving shock wave intensity at 0.55 mJ/mm 2 showed a significant decrease in sperm concentration, motility, and Johnsen score as compared to other groups. The apoptotic index of spermatogenic cells increased as the intensity of the shock wave treatment escalated, and reach a statistically significant difference at 4 weeks posttreatment. Treating testes with intensity levels of 0.55 mJ/mm 2 at 3 Hz interfere with the quality or quantity of spermatogenesis and also increases in spermatogenic cell apoptosis, whereas the expression of the SYCP3 gene significantly decreased after treatment with intensity levels of 0.10 mJ/mm 2 , 0.15 mJ/mm 2 , and 0.35 mJ/mm 2 at 4 Hz.

Conclusion: Treating testes with intensity levels of 0.55 mJ/mm 2 at 3 Hz interfere with the quality or quantity of spermatogenesis and also increases spermatogenic cell apoptosis, whereas the expression of the SYCP3 gene significantly decreased after treatment with intensity levels of 0.10 mJ/mm 2 , 0.15 mJ/mm 2 , and 0.35 mJ/mm 2 at 4 Hz.
J Chin Med Assoc. 2023 Feb 1;86(2):197-206. doi: 10.1097/JCMA.0000000000000838. Epub 2022 Nov 4. PMID: 36508688

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Comments 1

Jens Rassweiler on Monday, 27 February 2023 09:30

In the rat model, Li-ESWT has been shown to negatively impact semen concentration after treatment on the penis, implying that the reproductive system in close proximity may be indirectly affected by this modality.

The authors wanted with this study to evaluate the effect of shock waves on spermatogenesis after direct shockwave treatment on testes using different energy settings.

25 male Sprague Dawley rats, 8 weeks old, were divided into five groups, including one control group and four treatment groups (Storz Duolith SD) receiving 2000 shocks on the left testis twice a week for 4 weeks, with shock wave intensity and frequency varied by treatment group: 0.1 mJ/mm 2 at 4 Hz for Group A, 0.15 mJ/mm 2 at 4 Hz for Group B, 0.35 mJ/mm 2 at 4 Hz for Group C, and 0.55mJ/mm2 at 3 Hz for Group D. After 4 weeks, sperm collected from the epididymis was evaluated for concentration and motility. Testicular spermatogenesis, the apoptotic index of germ cells, and the expression of a meiotic-specific gene were also analyzed.

The left epididymal sperm concentration was found to be 160.4 ± 42.4 million/ml in the control group; and 156.2 ± 61.2, 236.4 ± 48.7, 211.4 ± 29.8 and 28.8 ± 12.9 million/ml in groups A, B, C and D. Thus, only high levels of shock wave energy had an impact. The same was observed concerning sperm motility: 70.6 ± 8.6 % in the control; and 70.4 ± 12.5 %, 72.6 ± 5.5%, 67.4 ± 9.3 % and 16.2 ± 7.8 % in groups A, B, C and D, respectively.

Histology of the left treated testicular tissue showed normal testicular architecture with an orderly arrangement of differentiating spermatogenic cells, Sertoli cells, and Leydig cells without histopathological lesions in groups A, B, and C. Whereas in group D, degeneration of Sertoli cells as well as disorganization of germ cell layers within affected seminiferous tubules was observed.

The serum testosterone levels did not differ significantly in all groups: 4.3 ± 2.3 ng/ml in the control; and 4.8 ± 3.4 ng/ml, 3.9 ± 0.9 ng/ml, 3.3 ± 1.8 ng/ml and 5.1 ± 3.1 ng/ml in groups A, B, C and D, respectively.

There was statistically significant increase in apoptotic index from 1.04 ± 0.25 %, 1.86 ± 0.38 %, 2.18 ± 0.22 % to 9.38 ± 1.98 % with increasing intensity levels across groups A, B, C and D, respectively. (p 0.05) in semen parameters was recorded in both groups. No significant difference in total testosterone levels was recorded after extracorporeal shock wave therapy compared to baseline (p = 0.584). The authors concluded that ESWT in erectile dysfunction and Peyronie’s disease patients does not seem to affect reproductive and hormonal testicular function.

On the other hand, Tian et al. 2022 found the contrary effect of Li-ESWT on scrotal tissue. Using an androgen-deficient model of the rat, they were able to stimulate the Leydig cells by enhanced VEGF-production. This would not fit to the theory of down regulation of SYCP3 mRNA levels in the testicular tissue observed by the authors. Thus, further clinical studies in this direction should be awaited.

Jens Rassweiler

In the rat model, Li-ESWT has been shown to negatively impact semen concentration after treatment on the penis, implying that the reproductive system in close proximity may be indirectly affected by this modality. The authors wanted with this study to evaluate the effect of shock waves on spermatogenesis after direct shockwave treatment on testes using different energy settings. 25 male Sprague Dawley rats, 8 weeks old, were divided into five groups, including one control group and four treatment groups (Storz Duolith SD) receiving 2000 shocks on the left testis twice a week for 4 weeks, with shock wave intensity and frequency varied by treatment group: 0.1 mJ/mm 2 at 4 Hz for Group A, 0.15 mJ/mm 2 at 4 Hz for Group B, 0.35 mJ/mm 2 at 4 Hz for Group C, and 0.55mJ/mm2 at 3 Hz for Group D. After 4 weeks, sperm collected from the epididymis was evaluated for concentration and motility. Testicular spermatogenesis, the apoptotic index of germ cells, and the expression of a meiotic-specific gene were also analyzed. The left epididymal sperm concentration was found to be 160.4 ± 42.4 million/ml in the control group; and 156.2 ± 61.2, 236.4 ± 48.7, 211.4 ± 29.8 and 28.8 ± 12.9 million/ml in groups A, B, C and D. Thus, only high levels of shock wave energy had an impact. The same was observed concerning sperm motility: 70.6 ± 8.6 % in the control; and 70.4 ± 12.5 %, 72.6 ± 5.5%, 67.4 ± 9.3 % and 16.2 ± 7.8 % in groups A, B, C and D, respectively. Histology of the left treated testicular tissue showed normal testicular architecture with an orderly arrangement of differentiating spermatogenic cells, Sertoli cells, and Leydig cells without histopathological lesions in groups A, B, and C. Whereas in group D, degeneration of Sertoli cells as well as disorganization of germ cell layers within affected seminiferous tubules was observed. The serum testosterone levels did not differ significantly in all groups: 4.3 ± 2.3 ng/ml in the control; and 4.8 ± 3.4 ng/ml, 3.9 ± 0.9 ng/ml, 3.3 ± 1.8 ng/ml and 5.1 ± 3.1 ng/ml in groups A, B, C and D, respectively. There was statistically significant increase in apoptotic index from 1.04 ± 0.25 %, 1.86 ± 0.38 %, 2.18 ± 0.22 % to 9.38 ± 1.98 % with increasing intensity levels across groups A, B, C and D, respectively. (p 0.05) in semen parameters was recorded in both groups. No significant difference in total testosterone levels was recorded after extracorporeal shock wave therapy compared to baseline (p = 0.584). The authors concluded that ESWT in erectile dysfunction and Peyronie’s disease patients does not seem to affect reproductive and hormonal testicular function. On the other hand, Tian et al. 2022 found the contrary effect of Li-ESWT on scrotal tissue. Using an androgen-deficient model of the rat, they were able to stimulate the Leydig cells by enhanced VEGF-production. This would not fit to the theory of down regulation of SYCP3 mRNA levels in the testicular tissue observed by the authors. Thus, further clinical studies in this direction should be awaited. Jens Rassweiler
Monday, 17 June 2024