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Background: Erectile dysfunction (ED) and weakness of the penis are processes related to hemodynamic alteration. Low-intensity pulsed ultrasound (LIPUS), as a new mechanical modality for the treatment of ED, deserves to be explored in depth for the biomechanical mechanisms it exerts., Objective: The aim of this study was to explore the role of YAP/TAZ-mediated mechanotransduction in mechanical therapy for the treatment of neurogenic erectile dysfunction (NED)., Materials and Methods: Forty-two male SD rats (12 w old) were randomly divided into sham-operated (n = 14), bilateral cavernous nerve injury (BCNI, n = 14), and LIPUS-treated (n = 14) groups. Intracavernosal pressure/mean arterial pressure (ICP/MAP) was measured 14 and 28 days after treatment. Penile tissue specimens were collected for pathological examination, and the changes in YAP, TAZ, connective tissue growth factor (CTGF), CYR61, LATS1, and p38 mitogen-activated protein kinase expression levels were assessed by Western blot, real-time quantitative polymerase chain reaction (RT-qPCR) and immunological staining., Results: Compared with BCNI, LIPUS significantly improved ICP/MAP levels and enhanced histopathological changes. The penile expression levels of YAP, TAZ, CTGF, and CYR61 were significantly downregulated in the BCNI group (p < 0.01), and LIPUS upregulated the expression levels of these proteins (p < 0.05). The expression levels of p-LATS1 and LATS1 were not significantly different among the groups (p > 0.05). Interestingly, the expression level of p-p38/p38 significantly increased in BCNI rats (p < 0.05), which was reversed by LIPUS treatment (p < 0.05). However, the p38 inhibitor SB203580 did not change the expression of YAP/TAZ in rat primary smooth muscle cells or mouse MOVAS cells (p > 0.05)., Discussion and Conclusion: LIPUS can effectively improve penile erectile function in NED rats. The underlying mechanism may be related to the regulation of YAP/TAZ-mediated mechanotransduction. However, the upstream regulatory signal may differ from the classical Hippo pathway., (© 2023 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Objective: To explore the preventive and therapeutic effects of Icariside Ⅱ (ICAⅡ) on radiation injury-induced ED (Ri-ED) in rats., Methods: Twenty-four 10-week-old male SD rats received exposure of the prostate to single X-ray irradiation of 20 Gy, and were randomly equally divided into an Ri-ED group (6 survived and 6 died) and a treatment group treated with ICAⅡ at 4.5 mg/kg/d (9 survived and 3 died). Another 6 SD rats were taken as negative controls. After 4 weeks of continuous intragastric administration and 2 weeks of drug elution, the erectile function of the rats was evaluated by measurement of the maximum intracavernous pressure / mean arterial pressure (ICPmax/MAP), and the penile tissues were subjected to immunofluorescence staining, immunohistochemistry, Masson's trichrome staining, Western blot and detection of oxidative stress indicators., Results: Compared with the negative controls, the rats in the Ri-ED group showed significant decreases in ICPmax/MAP (0.76 ± 0.09 vs 0.42 ± 0.06, P < 0.01), the number of nNOS-positive nerve fibers in the corpus cavernosum (10.17 ± 2.64 vs 3.17 ± 1.72, P < 0.01), the content of endothelial cells (1.39 ± 0.30 vs 0.35 ± 0.12, P < 0.01), the expressions of nNOS (0.42 ± 0.08 vs 0.08 ± 0.01, P < 0.01) and eNOS (0.99 ± 0.24 vs 0.12 ± 0.08, P < 0.01) and the activity of superoxide dismutase (SOD) (［343.73 ± 58.57］ vs ［153.50 ± 34.06］ U/mg prot, P < 0.01), but an increase in the malondialdehyde (MDA) level (［1.80 ± 0.31］ vs ［3.25 ± 0.21］ nmol/mg prot, P < 0.01). In comparison with the Ri-ED group, the animals treated with ICAⅡ exhibited remarkably increased ICP/MAP (0.42 ± 0.06 vs 0.66 ± 0.07, P < 0.01), number of nNOS-positive nerve fibers (3.17 ± 1.72 vs 7.33 ± 1.75, P < 0.05), content of endothelial cells (0.35 ± 0.12 vs 1.07 ± 0.36, P < 0.01), and expressions of nNOS (0.08 ± 0.01 vs 0.16 ± 0.05, P < 0.05) and eNOS (0.12 ± 0.08 vs 0.86 ± 0.30, P < 0.01) in the corpus cavernosum, but a decreased level of MDA (［3.25 ± 0.21］ vs ［2.17 ± 0.55］ nmol/mg prot, P < 0.05). In addition, ICAⅡ effectively reduced radiation injury-induced mortality of the rats., Conclusion: IcarisideⅡ can significantly improve ED and pathological changes and reduce mortality caused by radiation injury in rats, which may be related to its ability of improving radiation-induced oxidative stress.